september 7-8, 2021 department of chemical, biological

SEPTEMBER 7-8, 2021

Department of Chemical, Biological, Pharmaceutical and

Environmental Sciences

University of Messina

CINMPIS DAYS MESSINA

The Conference will be held online on the MICROSOFT TEAMS platform.

The National Interuniversity Consortium of Innovative Synthesis Methodologies and

Processes was established in 1994 and placed under the supervision of the Ministry of

University and Scientific and Technological Research in 1998. It has its registered

office at the University of Bari (Palazzo Ateneo) and administrative office at the

Department of Pharmacy – Pharmaceutical Sciences of the same University. It

currently includes 14 Italian Universities from all over Italy: South (Bari, Basilicata,

Salento, Calabria, Catania, Messina, Naples, Cagliari), Center (Camerino, Perugia,

Florence) and North (Bologna, Pavia and Milan-Bicocca). From its foundation it was

directed by Prof. Saverio Florio until 2013, and subsequently by Prof. Alberto Brandi

(2013-2016). CINMPIS is currently headed by Prof. Vito Capriati of the University of

Bari.

SCIENTIFIC COMMITTEE

Vito Capriati, University of Bari

Antonio Rescifina, University of Catania

Maurizio D’Auria, University of Basilicata

Bartolo Gabriele, University of Calabria

Filippo Doria, University of Pavia

Franz Kohnke, University of Messina

Andrea Temperini, University of Perugia

Cristina Nativi, University of Firenze

Francesco Peri, University of Milano-Bicocca

Andrea Porcheddu, University of Cagliari

Marino Petrini, University of Camerino

Daniela Montesarchio, University of Napoli Federico II

Antonio Salomone, University of Salento

Marco Bandini, University of Bologna

LOCAL COMMITTEE

Franz Kohnke

Melchiorre Parisi

Anna Notti

Anna Barattucci

Salvatore V. Giofrè

CINMPIS DAYS: PREVIOUS EDITIONS

I Pavia, October 9, 2001 (University of Pavia)

II L’Aquila, October 28, 2002 (DOMPE’ SpA)

III Lecce, September 18-19, 2003 (University of Lecce)

IV Firenze, October 22, 2004 (University of Firenze)

V Bari, November 7, 2005 (University of Bari)

VI Bologna, October 13, 2006 (University of Bologna)

VII Napoli, November 29, 2007 (University of Napoli Federico II)

VIII Milano, November 25, 2008 (University Statale di Milano)

IX Padova, September 2, 2009 (Complesso San Gaetano)

X San Benedetto (AP), September 17, 2010 (Convention Center “PalaRiviera”)

XI Bari, November 25, 2011 (University of Bari)

XII Milano, December 3, 2012 (University of Milano-Bicocca).

XIII Perugia, December 18, 2013 (University of Perugia)

XIV Bari, September 29-30, 2014 Ventennium Conference (University of Bari)

XV Napoli, December 11-12, 2015 (University of Napoli Federico II)

XVI Rende, Campus Scientifico, December 16-17, 2016 (University of Calabria)

XVII Cagliari, December 15-16, 2017 (University of Cagliari).

XVIII Bologna, February 18-19, 2019 (University of Bologna).

XIX Pavia, February 20-21, 2020 (University of Pavia)

CINMPIS LECTURES

CINMPIS Lecturer 2012 Prof. Ilan Marek, Technion – Istrael Institute of Technology,

Haifa, Israel

CINMPIS Lecturer 2017: Prof. Dieter Seebach, ETH Zürich

CINMPIS Lecturer 2018: Prof. dr. Syuzanna R. Harutyunyan, University of Groningen

PRIZEWINNERS: Innovation in Organic Synthesis

2004 Andrea Basso (University of Genova)

2005 Marco Lombardo (University of Bologna)

2006 Leonardo Manzoni (ISTM-CNR Milano) & Ernesto Giovanni Occhiato (University

of Firenze)

2007 Pier Giorgio Cozzi (University of Bologna)

2008 Gianluca Maria Farinola (University of Bari)

2009 Vito Capriati (University of Bari)

2010 Stefano Cicchi (University of Firenze)

2011 Maurizio Fagnoni (University of Pavia)

2012 Laura Cipolla (University of Milano-Bicocca)

2013 Cosimo Cardellicchio (CNR-ICCOM)

2014 Maurizio Benaglia (University of Milano) & Renzo Luisi (University of Bari)

2015 Serena Perrone (University of Salento)

2016 Alessandro Abbotto (University of Milano-Bicocca)

2017 Raffaella Mancuso (University of Calabria)

2018 Oscar Francesconi (University of Firenze)

2019 Daniela Montesarchio (University of Napoli Federico II)

2020 Stefano Menichetti (University of Firenze)

PRIZEWINNERS: Best Ph.D. Thesis

2003 Luigi Anastasia (University of Milano)

2004 Luca Bernardi (University of Bologna)

2005 Matilde Guala (University of Pavia) & Carlo Punta (Politecnico di Milano)

2006 Alberto Bossi (University of Milano)

2007 Stefano Protti (University of Pavia)

2008 Giacomo Ghini (University of Firenze)

2009 Anna Llanes-Pallas (University of Trieste)

2010 Patrizia Galzerano (University of Bologna)

2011 Elisa Mosconi (University of Bologna)

2012 Alex Manicardi (University of Parma)

2013 Nicola Castellucci (University of Bologna)

2014 Eleonora Tenori (University of Firenze) & Michele Mingozzi (University of

Milano)

2015 Massimo Manuelli (University of Firenze)

2016 Stefano Fedeli (University of Firenze) & Vincenzo Campisciano (University of

Palermo)

2017 Luka Ðorđević (University of Trieste)

2018 Gianluca Salerno (University of Firenze) & Claudia Riccardi (University of Napoli

Federico II)

2019 Giulio Bertuzzi (University of Bologna)

2020 Marco Colella (University of Bari)

SPEAKERS CINMPIS DAYS 2021

CINMPIS LECTURES

CINMPIS Lecturer 2019

Prof. Karl Anker Jørgensen Aarhus University

“Expanding the borders of reactivity in

organic chemistry”

CINMPIS Lecturer 2021

Prof. M. Carmen Carreño Madrid Autonomous University

“Progress in synthesis mediated by sulfoxides: natural products and

molecular switches”

KEYNOTE SPEAKER

Prof. Silvia Vignolini Cambridge University

“Colour with a twist: from

cellulose to large scale production of interference

pigments”

PRIZE LECTURES

Innovation in Organic Synthesis

Prizewinner 2020

Prof. Stefano Menichetti University of Firenze

“Synthesis of [n]heterohelicenes: a modern twist in our chemistry”

Prizewinner 2021

Prof. Marco Lombardo University of Bologna

“1,2-Dioxanes as potential agents

against malaria and human leishmaniasis”

PRIZE LECTURES

Best Ph.D. Thesis

Prizewinner 2020

Dr. Marco Colella University of Bari

“Flow microreactors as enabling technology for the genesis and

use of (highly) reactive organolithium reagents”

Prizewinner 2021

Dr. Antonia Rinaldi University of Firenze

“New gold(I)-catalyzed cascade reactions for the synthesis of pentannulated n-hetero- and

carbacycles”

SCIENTIFIC PROGRAMME

7th September 2021

9:00–9:15 Opening Cerimony

Chairperson: Vito Capriati (University of Bari)

9:15–10:00 PL1 Karl Anker Jørgensen (University of Aarhus)

Expanding the borders of reactivity in organic chemistry

Session 1 Chairperson: Marco Bandini (University of Bologna)

10:00–10:30 KN1 Stefano Menichetti (University of Firenze)

Synthesis of [n]heterohelicenes: a modern twist in our chemistry

Session 2 Chairperson: Maurizio D’Auria (University of Basilicata)

10:30-10:45 OC1 Elena Lenci (University of Firenze)

Developing selective matrix metalloproteinase inhibitors for targeted anticancer therapy

10:45–11:00 OC2 Federico Cuccu (University of Cagliari)

Mechanosynthesis of sulfur-containing drugs

11:00–11:45 Break

Session 3 Chairperson: Bartolo Gabriele (University of Calabria)

11:45–12:00 OC3 Serena Traboni (University of Napoli Federico II)

Less is more: solvent-free approaches to address synthetic challenges in carbohydrate chemistry

12:00–12:15 OC4 Chiara Liliana Boldrini (University of Milano-Bicocca)

Eco-friendly deep eutectic solvent electrolyte solutions for dye-sensitized solar cells

12:15–12:30 OC5 Lorenzo Lombardi (University of Bologna)

Nickel catalyzed tandem ring expansion-carboxylation of cyclobutanones with CO2

12:30–12:45 OC6 Gianfranco Decandia (University of Bari)

Infrared irradiation-assisted Pd-catalyzed direct (hetero)arylation polymerization

12:45–13:00 OC7 Valentina Pirota (University of Pavia)

Peg-like chains make naphthalene diimide-copper complexes more suitable for parallel G-

quadruplexes

13:00–14:30 Lunch break

Session 4 Chairperson: Andrea Porcheddu (University of Cagliari)

14:30–15:00 KN2 Marco Colella (University of Bari)

Flow microreactors as enabling technology for the genesis and use of (highly) reactive

organolithium reagents

Session 5 Chairperson: Marino Petrini (University of Camerino)

15:00–15:15 OC8 Dario Gentili (University of Camerino)

A new chiral auxiliary in the cerium-catalyzed enatioselective Nazarov ciclization/decarboxilation

15:15–15:30 OC9 Italo Franco Coelho Dias (University of Perugia)

Development of new selenium-based strategies for the synthesis of heterocycles

15:30–15:45 OC10 Giuseppe Dilauro (University of Bari)

Scalable palladium-catalysed Negishi cross-coupling reactions between organozinc reagents and

(hetero)aryl bromides in nonconventional solvents

15:45–16:15 Break

Session 6 Chairperson: Daniela Montesarchio (University of Napoli Federico II)

16:15–16:30 OC11 Vincenzo Patamia (University of Catania)

Nanosponges based on self-assembled starfish-shaped cucurbit[6]urils functionalized with

imidazolium arms

16:30–16:45 OC12 Anna Laura Sanna (University of Cagliari)

Photochromic torsional switches (pts) towards light-responsive / self-tuning organic semiconductors

16:45–17:00 OC13 Pantaleo Musci (University of Bari)

Exploring the potential of metallated strained heterocycles: flow generation, lithiation and

functionalization of 1-azabicyclo[1.1.0]butanes

17:00–17:15 OC14 Ettore Napolitano (University of Napoli Federico II)

A selective fluorescent light-up aptameric system for diagnostics and theranostics

17:15-17:30 OC15 Gianluigi Albano (University of Bari)

IR irradiation-assisted solvent-free Palladium-catalyzed direct and dehydrogenative (hetero)aryl-

aryl coupling

8th September 2021

Chairperson: Franz H. Kohnke (University of Messina)

9:00–9:45 PL2 M. Carmen Carreño (Autonomous University of Madrid)

Progress in synthesis mediated by sulfoxides: natural products and molecular switches

Session 7 Chairperson: Francesco Peri (University of Milano-Bicocca)

9:45–10:15 KN3 Marco Lombardo (University of Bologna)

1,2-Dioxanes as potential agents against malaria and human leishmaniasis

Session 8 Chairperson: Filippo Doria (University of Pavia)

10:15–10:30 OC16 Serena Perrone (University of Salento)

Green and safe hydrogenations in deep eutectic solvents

10:30–10:45 OC17 Giulia Rando (University of Messina)

Pillararene-based PDMAEMA/PES blended polymers: a new supramolecular approach towards

environmental remediation

10:45–11:00 OC18 Giorgio Rizzo (University of Bari)

Palladium supported on silk fibroin as a robust and versatile coupling catalyst

11:00–11:45 Break

Session 9 Chairperson: Cristina Nativi (University of Firenze)

11:45–12:15 KN4 Silvia Vignolini (University of Cambridge)

Colour with a twist: from cellulose to large scale production of interference pigments

Session 10 Chairperson: Antonio Rescifina (University of Catania)

12:15–12:30 OC19 Marco Milone (University of Messina)

Tuning the self-assembly of calix[4]tube derivatives

12:30–12:45 OC20 Francesco Secci (University of Cagliari)

Exploring the reactivity of 2-hydroxy cyclobutanone derivatives

12:45–13:00 OC21 Michael Andresini (University of Bari)

Synthesis of Protected Sulfilimines from Sulfinimidate Esters

13:00–14:30 Lunch break

Session 11 Chairperson: Andrea Temperini (University of Perugia)

14:30–15:00 KN5 Antonia Rinaldi (University of Firenze)

New gold(I)-catalyzed cascade reactions for the synthesis of pentannulated n-hetero- and

carbacycles

15:00–15:15 OC22 Cristina Decavoli (University of Milano-Bicocca)

Organic dye-based dyads for the production of solar fuels

15:15–15:30 OC23 Alessandra Tolomelli (University of Bologna)

Steps in the journey toward green solid phase peptide synthesis (GSPPS)

15:30–15:45 OC24 Giulia Neri (University of Messina)

Multifunctional fluorescent graphene-cyclodextrin nanoplatforms

Session 12 Chairperson: Vito Capriati (University of Bari)

15:45–16:00 OC25 Federico Casti (University of Cagliari)

New catalysts in green chemistry

16:00–16:15 OC26 Francesco Milanesi (University of Firenze)

Synthesis of a thio-analogue of sialyllactose to tagret mumps virus neuraminidase

16:15 Closing Remarks

CINMPIS Days Messina 2021 PL 1

EXPANDING THE BORDERS OF REACTIVITY IN ORGANIC CHEMISTRY

Karl Anker Jørgensen

Department of Chemistry, Aarhus University, DK-8000 Aarhus C

[email protected]

Cycloadditions have occupied a crucial place in the synthetic chemist’s toolbox for decades. The

ability to form multiple covalent bonds in a single transformation allows for rapid generation of

complex scaffolds. This has been expanded by the use of chiral catalysts and auxiliaries that allow

for the controlled synthesis of multiple stereocenters simultaneously.

These reactions were greatly affected by the work of Woodward and Hoffmann, which remain

paramount in of organic chemistry and stand as a testimonial to the benefit of fully understanding

the physical nature of a class of reactions. It is through the Woodward-Hoffmann rules that

research has expanded in the world of cycloadditions using their forbidden/allowed criterion to lead

the development of reactions.

Recently, cycloadditions containing more than 6-electrons—termed “higher-order

cycloadditions”—have become novel reaction concepts to generate chemical complexity in a

single transformation. The lecture will present the development of novel reaction concepts for

higher-order cycloadditions based on organocatalysis and integrate both synthetic developments,

menhanistic investigations, we well as bioactivity studies.

The lecture will also present the organocatalytic oxidative coupling concepts for the coupling of

two nucleophiles, such as carboxylic acids, thiols, indoles, phenoles/alcohols, and amino acids

and peptides to the -position of aldehydes. Different reaction concepts and mechanistic

investigations will be outlined, and it is demonstrated that these oxidative coupling reactions can

be used for bioconjugation.

CINMPIS Days Messina 2021 PL 2

PROGRESS IN SYNTHESIS MEDIATED BY SULFOXIDES: NATURAL PRODUCTS AND MOLECULAR SWITCHES

M. Carmen Carreño

Departamento de Química Orgánica, Módulo 01, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco 28049 Madrid, Spain.

e-mail: [email protected]

The efficacy of sulfoxides in diastereoselective auxiliary-induced reactions is nowadays well established. Their easy elimination and possible transformations into other functions increase their synthetic usefulness. This lecture will highlight the most relevant applications of enantiopure sulfoxides in synthesis of structurally complex molecules mainly based on Diels-Alder reactions and conjugate additions. Bioactive Angucyclinones and polycyclic helical quinones were easily accessible from sulfinyl quinones and p-quinols. Natural p-quinol derivatives and polyhydroxy substituted targets were synthesized starting form p-alkyl phenols in a short manner, using of Oxone® as a source of singlet oxygen. The sulfoxide was shown to control the stereochemistry of the photoisomerization process of azobenzenes in enantiopure molecular switches.

mailto:[email protected]

CINMPIS Days Messina 2021 KN 1

SYNTHESIS OF [n]HETEROHELICENES: A MODERN TWIST IN OUR CHEMISTRY

Stefano Menichetti

Department of Chemistry ‘Ugo Schiff’, University of Florence, Via Della Lastruccia 3-13, 50019, Sesto Fiorentino, Firenze, Italy


Helicenes and heterohelicenes are challenging chiral structures that continuously stimulate new interest and find new applications. From just a chemical curiosity related with their inherent chirality, these compounds are now commonly used in asymmetric synthesis, medicinal chemistry and, above all, material science. In the last years we became interested in the chemistry of heterohelicenes and described new approaches for their synthesis. For example, we demonstrated that the Povarov reaction (Figure 1) can be exploited for the synthesis of [n]azahelicenes [1].

Figure 1

At the same time, thia-bridged triarylamine[4]helicenes can be prepared using consecutive regioselective electrophilic sulfur insertions on triarylamines or N-arylphenothiazine skeletons (Figure 2). Due to the long carbon-sulfur bonds, these systems belong to the valuable family of stereochemically stable [4]helicenes, with racemization barriers as high as 31-32 Kcal/mol, and show very promising applications [2].

Figure 2

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[1] C. Viglianisi, C. Biagioli, M. Lippi, M. Pedicini, C. Villani, R. Franzini, S. Menichetti Eur. J. Org. Chem. 2019, 164-167. [2] a) G. Lamanna, C. Faggi, F. Gasparrini, A. Ciogli, C. Villani, J. P. Stephens, J. F. Devlin,; S. Menichetti,

Chem-Eur. J., 2008, 14, 5747-5750; b) S. Menichetti, S. Cecchi, P. Procacci, M. Innocenti, L. Becucci, L. Franco, C. Viglianisi Chem. Commun. 2015, 51, 11452-11453; c) N. Giaconi, A. L. Sorrentino, L.

Poggini, M. Lupi, V. Polewczyk, G. Vinai, P. Torelli, A. Magnani, R. Sessoli, S. Menichetti, L. Sorace, C. Viglianisi, M. Mannini Angew. Chem. Int. Ed. 2021, 60, 15276–15280; d) R. Amorati, L.Valgimigli, A.

Baschieri, Y. Guo, F. Mollica, S. Menichetti, M. Lupi, C. Viglianisi ChemPhysChem, 2021, 22, 1446-1454;

e) M. Lupi, S. Menichetti, P. Stagnaro, R. Utzeri, C. Viglianisi Synthesis 2021, 53, 2602–2611.



FLOW MICROREATORS AS ENABLING TECHNOLOGY FOR THE GENESIS AND USE OF (HIGHLY) REACTIVE ORGANOLITHIUM REAGENTS Marco Colella,a,* Arianna Tota,a Pantaleo Musci, a Leonardo Degennaro,a Renzo Luisi a

a Department of Pharmacy – Drug Sciences, University of Bari “A. Moro” Via E. Orabona 4, 70125 – Italy FLAME-Lab –Flow Chemistry and Microreactor Technology Laboratory

* e-mail: [email protected]

In the era of breathtaking technological advances, scientists have new tools for supporting fundamental science, thus having the opportunity to face unresolved challenges, and to explore new possibilities [1]. In the field of organic synthesis, the advent of flow chemistry and flow microreactor technology allowed the refining of various synthetic methodologies offering the possibility to explore transformations impossible to run using batch methods [2, 3]. In this contribution, our recent efforts on the use of flow microreactor technology for the genesis and use of short-lived organolithium intermediates will be presented. In this context, specific attention will be devoted to the development of new fluorination strategies exploiting fluorinated lithium carbenoids [4, 5, 6, 7]. Furthermore, the benefits of flow microreactor technology in taming other lithiated short-lived intermediates will be described [8, 9].

Figure. Flow microreator technology for the genesis and use of short-lived organolithium reagents.

____

[1] G. S. Omenn, Science 2006, 314, 1696. [2] B. Guttman, C.O. Kappe, J. Flow Chem, 2017, 7, 65.

[3] M. Colella, A. Nagaki, R. Luisi. Chem.–Eur. J., 2020, 26, 19. [4] G. Parisi, M. Colella, S. Monticelli, G. Romanazzi, W. Holzer, T. Langer, L. Degennaro, V. Pace, R.

Luisi. J. Am. Chem. Soc., 2017, 139, 13648. [5] S. Monticelli, M. Colella, V. Pillari, A. Tota, T. Langer, W. Holzer, L. Degennaro, R. Luisi, V. Pace.

Org. Lett., 2019, 21, 584.

[6] M. Colella, A. Tota, A. Großjohann, C. Carlucci, A. Aramini, N. S. Sheikh, L. Degennaro, R. Luisi. Chem. Commun., 2019, 55, 8430.

[7] M. Colella, A. Tota, Y.Takahashi, R. Higuma, S. Ishikawa, L. Degennaro, R.Luisi, A. Nagaki. Angew. Chem. Int. Ed., 2020, 59, 10924.

[8] P. Musci, M. Colella, A. Sivo, G. Romanazzi, R. Luisi, L. Degennaro. Org. Lett., 2020, 22, 3623.

[9] Y. Takahashi, Y. Ashikari, M. Takumi, Y. Shimizu, Y. Jiang, R. Higuma, S. Ishikawa, H. Sakaue, I. Shite, K. Maekawa, Y. Aizawa, H.Yamashita, Y. Yonekura, M. Colella, R.Luisi, T. Takegawa, C. Fujita, A.

Nagaki. Eur. J. Org. Chem., 2020, 2020, 618. Y. Takahashi, Y. Ashikari, M. Takumi, Y. Shimizu, Y. Jiang, R. Higuma, S. Ishikawa, H. Sakaue, I. Shite, K. Maekawa, Y. Aizawa, H.Yamashita, Y. Yonekura,

M. Colella, R.Luisi, T. Takegawa, C. Fujita, A. Nagaki


1,2-DIOXANES AS POTENTIAL AGENTS AGAINST MALARIA AND HUMAN LEISHMANIASIS

Marco Lombardo*

a Department of Chemistry “G. Ciamician", University of Bologna, Bologna, Italy


Malaria and human leishmaniasis are two of the most troublesome neglected tropical diseases, which are endemic in hundreds of countries around the world. They are linked to poverty and poor sanitation systems, putting the life of millions of people in underdeveloped countries at risk every year, being especially dangerous for children under 5 years of age, for pregnant women and for patients with other immunodeficiency infections (HIV/AIDS). Artemisinin (1) and its derivatives have shown a very good efficacy against protozoan parasites such as Plasmodium, and are widely used for the treatment of malaria. Some synthetic peroxides, i.e. tetraoxanes (2) or trioxolanes (3), are now considered valid alternatives to artemisinin-derived drugs and some of them are actively studied in clinical trials as anti-malarials. Much less is known about the antiparasitic activity of peroxides against Leishmania, but some recent reports observed micromolar activities of peroxide derivatives. Here we report our recent studies on the synthesis and on the anti-malarial and anti-leishmanial activity of a selected group of synthetic 1,2-dioxanes (4) with overall good performances in terms of potency and selectivity, making them promising candidates for a preliminary lead optimization as antiparasitic agents.[1] Finally, the preparation and the bioactivity of tetrahydropyranes 5, lacking the peroxide moiety, will be discussed in order to shed some light on the actually unknown mechanism of action of synthetic peroxides against Leishmania parasites.

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[1] M. Persico, A. Quintavalla, F. Rondinelli, C. Trombini, M. Lombardo, C. Fattorusso, V. Azzarito, D. Taramelli, S. Papini, Y. Corbett, G. Chianese, E. Fattorusso, O. Taglialatela-Scafati J. Med. Chem. 2011, 54, 8526-8540; M. Persico, S. Parapini, G. Chianese, C. Fattorusso, M. Lombardo, L. Petrizza, A. Quintavalla, F. Rondinelli, N. Basilico, D. Taramelli, C. Trombini, E. Fattorusso, O. Taglialatela-Scafati Eur. J. Med. Chem. 2013, 70, 875-886; M. Lombardo, D. P. Sonawane, A. Quintavalla, C. Trombini, D. D. Dhavale, D. Taramelli, Y. Corbett, F. Rondinelli, C. Fattorusso, M. Persico, O. Taglialatela-Scafati Eur. J. Org. Chem. 2014, 1607–1614; D. P. Sonawane, Y. Corbett, D. D. Dhavale, D. Taramelli, C. Trombini, A. Quintavalla, M. Lombardo Org. Lett. 2015, 17, 4074–4077; D. P. Sonawane, M. Persico, Y. Corbett, G. Chianese, A. Di Dato, C. Fattorusso, O. Taglialatela-Scafati, D. Taramelli, C. Trombini, D. D. Dhavale, A. Quintavalla, M. Lombardo RSC Adv., 2015, 5, 72995–73010; M. Persico, R. Fattorusso, O. Taglialatela-Scafati, G. Chianese, I. de Paola, L. Zaccaro, F. Rondinelli, M. Lombardo, A. Quintavalla, C. Trombini, E. Fattorusso, C. Fattorusso, B. M. Farina Scientific Reports 2017, 7, 45485; M. Ortalli, S. Varani, A. Quintavalla, M. Lombardo, C. Trombini Eur. J. Med. Chem 2019, 170, 126–140; M. Ortalli, S. Varani, G. Cimato, R. Veronesi, A. Quintavalla, M. Lombardo, M. Monari, C. Trombini J. Med. Chem. 2020, 63, 13140–13158


COLOUR WITH A TWIST: FROM CELLULOSE TO LARGE SCALE PRODUCTION OF INTERFERENCE PIGMENTS

Silvia Vignolini

University of Cambridge, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK


By designing the dimensions of such nanostructures, it is possible to achieve extremely intense colourations over the entire visible spectrum without using pigments or colorants. Colour obtained through structure, namely structural colour, is widespread in the animal and plant kingdom [1]. Such natural photonic nanostructures are generally synthesised in ambient conditions using a limited range of biopolymers. Given these limitations, an amazing range of optical structures exists: from very ordered photonic structures [2], to partially disordered [3], to completely random ones [4]. In this seminar, I will introduce some striking example of natural photonic structures [2-4] and share some insight on their development. Then I will review our recent advances to fabricate bio-mimetic photonic structures using the same material as nature. Developing biomimetic structures with cellulose enables us to fabricate novel photonic materials using low cost polymers in ambient conditions [6-7]. Importantly, it also allows us to understand the biological processes at work during the growth of these structures in plants.

[1] Kinoshita, S. et al. (2008). Physics of structural colors. Rep. Prog. Phys. 71(7), 076401.

[2] Vignolini, S. et al. (2012). Pointillist structural color in Pollia fruit. PNAS 109, 15712-15716.

[3] Moyroud, E. et al. (2017). Disorder in convergent floral nanostructures enhances signalling to bees. Nature 550, 469.

[4] Burresi M. et al. (2014) Bright-White Beetle Scales Optimise Multiple Scattering of Light. Sci. Rep. 4, 727

[5] Parker R. et al. (2018) The Self-Assembly of Cellulose Nanocrystals: Hierarchical Design of Visual Appearance. Adv Mat 30, 1704477 [6] Parker R. et al. (2016). Hierarchical Self-Assembly of Cellulose Nanocrystals in a Confined Geometry. ACS Nano, 10 (9), 8443–8449

[7] Liang H-L. et al. (2018). Roll-to-roll fabrication of touch-responsive cellulose photonic laminates, Nat Com 9, 4632


NEW GOLD(I)-CATALYZED CASCADE REACTIONS FOR THE SYNTHESIS OF PENTANNULATED N-HETERO- AND CARBACYCLES

Antonia Rinaldi,a* Vittoria Langè,a Dina Scarpi,a Ernesto G. Occhiatoa

aDepartment of Chemistry “U. Schiff”, University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy

*e-mail: [email protected]

Nowadays, cascade reactions promoted by transition metal complexes play a significant role

in organic synthesis, leading to the assembly of complex frameworks with a high atom

economy, reducing both chemical waste and reaction time. On this ground, the alkynophilicity

of gold(I) catalysts was investigated to promote the formation of systems which can be further

elaborated in situ. Suitably substituted propargyl vinyl ethers 1 undergo a propargyl Claisen

rearrangement/Nazarov cyclization (or hydroarylation reaction) cascade process to efficiently

provide functionalized cyclopentadienes fused with various N-hetero- and carbacycles 2,

including indenes and cyclopenta[b]indoles.[1,2] These products can be subjected in situ to

various reactions, allowing for the facile construction of important intermediates for the

synthesis of many natural and biologically active compounds, such as indane and polycyclic

derivatives.[3] To demonstrate the usefulness of this cascade process, the strategy was

applied for the synthesis of a natural product, (±)-epi-Jungianol.[4]

____

[1] Rinaldi A., Petrovic M., Magnolfi S., Scarpi D., Occhiato E. G., Org. Lett. 2018, 20, 4713−4717. [2] Rinaldi A., Langé V., Gomez E., Zanella G., Scarpi D., Occhiato, E. G., J. Org. Chem. 2019, 84,

6298−6311.

[3] Rinaldi A., Langé V., Scarpi D., Occhiato E. G., J. Org. Chem. 2020, 85, 5078–5086. [4] Rinaldi A., Langé V., Scarpi D., Occhiato E. G., Eur. J. Org. Chem. 2021, 8, 1266−1273.

CINMPIS Days Messina 2021 OC 1

DEVELOPING SELECTIVE MATRIX METALLOPROTEINASE INHIBITORS FOR TARGETED ANTICANCER THERAPY

Elena Lenci,a,* Alessandro Contini,b Andrea Trabocchi,a,c

a Department of Chemistry “Ugo Schiff”, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy

b Department of Pharmaceutical Sciences, University of Milan, Via Venezian 21, I-20133 Milan, Italy

c Interdepartmental Center for Preclinical Development of Molecular Imaging (CISPIM), University of Florence, Viale Morgagni 85, 50134 Florence, Italy


Despite a high degree of structural similarity, it is known that MMP2 and MMP9 have distinct roles in the angiogenic switch and in cell migration, as they activate diverse signaling pathways. Indeed, inhibition of MMP2 and MMP9 can show beneficial or detrimental effects depending on the stage of tumor progression [1]. Thus, the selective inhibition of gelatinases is of relevance for a successful drug lead, which has to be achieved despite the high structural similarity of the two gelatinases. Herein, we present our recent synthetic efforts in the development of highly selective MMP2 and/or MMP9 inhibitors based on the D-proline scaffold. In particular, the synthesis of D-proline-derived hydroxamic acids containing diverse appendages at the amino group, varying in length and decoration, allowed to give insight on the MMP2/MMP9 selectivity around the S1’ subsite, resulting in the identification of sub-nanomolar compounds with high selectivity up to 730 [2]. Also, the synthesis and evaluation of D-proline derivatives containing amino appendages at C-4 enabled the identification of a > 200-fold selective MMP9 inhibitor, thus addressing gelatinase selectivity beyond the S1′ subsite [3]. Finally, the synthesis and enzyme inhibition kinetics of D-proline derivatives containing a biphenyl sulfonamido moiety revealed an interesting inhibition profile towards MMP9 and CAII. As MMP9 and CAII enzymes are both overexpressed in gastrointestinal stromal tumor cells, these molecules may represent interesting chemical probes for a multitargeting approach on gastric and colorectal cancer [4].

____

[1] R.E. Vandenbroucke, C. Libert, Nat. Rev. Drug Discov. 2014, 13, 904-927

[2] E. Lenci, R. Innocenti, T. Di Francescantonio, G. Menchi, F. Bianchini, A. Contini, A. Trabocchi, Bioorg. Med. Chem. 2019, 27, 1891-1902.

[3] E. Lenci, A. Contini, A. Trabocchi, Bioorg. Med. Chem. Lett. 2020, 30, 127467.

[4] E. Lenci, A. Angeli, L. Calugi, R. Innocenti, F. Carta, C. T. Supuran, A. Trabocchi, Eur. J. Med. Chem. 2021, 214, 113260


MECHANOSYNTHESIS OF SULFUR-CONTAINING DRUGS

Federico Casti,a Andrea Porcheddu,a Federico Cuccu,a*

a Dipartimento di Scienze Chimiche e Geologiche, University of Cagliari, Monserrato, Sardinia, Italy.


In the last two decades, mechanochemistry has been extensively studied with particular referment to Green Chemistry and its principles [1]. In 2019, IUPAC described this mechanical technique of the ten most important innovations to change thinking chemistry [2]. The need for a “greener approach” to obtain API (Active Pharmaceutical Ingredients) moved the interest of many pharmaceutical companies in cooperation with academia. Ball mill and extruders are widely used to perform this reaction and grant high performance in solid-phase synthesis. Herein, some highlights from the most recent results will be presented, paying particular attention to greener paths for the synthesis of sulfur-containing drugs by a ball mill approach.

____

[1] Porcheddu, A., Metal-Mediated and Metal-Catalyzed Reactions Under Mechanochemical Conditions,

ACS Catal. 2020, 10, 15, 8344–8394

[2] Gomollon-Bel, F., Ten Chemical Innovations That Will Change Our World, Chem Int, 41(2), pp. 12-17, 2019.

+


LESS IS MORE: SOLVENT-FREE APPROACHES TO ADDRESS SYNTHETIC CHALLENGES IN CARBOHYDRATE CHEMISTRY

Serena Traboni,a,* Emiliano Bedini,a Giulia Vessella,a Alfonso Iadonisia

a Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, 80126, Naples


Carbohydrates are widespread in nature and represent fundamental synthetic targets for biomedical research as well as convenient precursors of a wide range of compounds applicable in diverse scientific fields.[1] However, their peculiar structural features give rise to a significant complexity in their synthetic manipulation. Major issues are represented by the laborious regioselective installation of orthogonal protecting groups to differentiate the many reactive sites, as well as by the frequent need of operating under rigorously anhydrous conditions and, not least, by the routine use of high-boiling, toxic and polluting organic solvents. To overcome these issues, several efforts have been addressed to the development of one-pot methodologies for protection and glycosylation of carbohydrates,[2] as well as to the introduction of more sustainable and environmentally friendly approaches in their synthetic elaborations.[3] In most cases these are however expensive in terms of the chemicals and equipment needed and entail non-trivial experimental protocols. In this communication is presented an overview of recent results from our laboratory concerning the development of new simplified and inexpensive procedures for synthetic transformations of carbohydrates, entirely performable under air in the absence of any solvent.[4] In the first part, it is illustrated the efficiency of solvent-free approaches in the regioselective installation of several protecting group classes, including benzyl/allyl ethers, acetals, silyl and trityl groups, as well as in the conversion of saccharide hydroxyls in other functionalities, useful as either leaving groups (such as iodide and tosylate) or as precursors for conjugation reactions (such as azide and thioacetate groups). Contextually, it is also discussed the feasible merging of these procedures into one-pot sequences for a straightforward assembly of orthogonally functionalized building-blocks. In the second part of the communication, it is presented the applicability of solvent-free methodologies in glycosylation chemistry with a particular focus on the preparation of glycosyl chlorides and their efficient performance as glycosyl donors in the complex construction of -glycosidic linkages.

____

[1] a) S. Hanessian, “Total Synthesis of Natural Products: The 'Chiron' Approach”, Pergamon Press, Elmsford. NY, 1983; b) C. Chatterjee, F. Pong, A. Sen, Green Chem. 2015, 17, 40-71.

[2] a) C.-C. Wang, J.-C. Lee, S.-Y. Luo, S. S. Kulkarni, Y.-W. Huang, C.-C. Lee, K.-L. Chang, S.-C. Hung, Nature 2007, 446, 896-899; b) A. Francais, D. Urban; J.-M. Beau, Angew. Chem. Int. Ed. 2007, 46,

8662-8665; c) S. S. Kulkarni, C.-C. Wang, N. M. Sabbavarapu, A. R. Podilapu, P.-H. Liao, S.-C. Hung, Chem. Rev. 2018, 118, 8025-8104.

[3] a) A. Si, A. K. Misra, Recent Trends in Carbohydrate Chemistry, 1 - Perspective on the Transformation of Carbohydrates Under Green and Sustainable Reaction Conditions, Elsevier, 2020; b) A. Perona, P. Hoyos, A. Farrán, M. J. Hernáiz, Green Chem. 2020, 22, 5559-5583.

[4] For a recent review on solvent-free approaches in carbohydrate synthetic chemistry including the herein presented contributions from our laboratory: S. Traboni, E. Bedini, G. Vessella, A. Iadonisi,

Catalysts 2020, 10, 1142-1164.


ECO-FRIENDLY DEEP EUTECTIC SOLVENT ELECTROLYTE SOLUTIONS FOR DYE-SENSITIZED SOLAR CELLS

C. L. Boldrinia,*, N. Manfredia, F. M. Pernab, V. Capriatib, A. Abbottoa

a Dipartimento di Scienza dei Materiali, Università degli Studi di Milano-Bicocca, and INSTM Milano-Bicocca Research Unit, 20125 Milano, Italy; b Dipartimento di Farmacia–Scienze del Farmaco,

Università degli Studi di Bari “Aldo Moro”, Consorzio C.I.N.M.P.I.S., 70125 Bari, Italy


Among photovoltaics technologies, dye-sensitized solar cells (DSSCs) offer high conversion efficiencies (15% record efficiency) and low-cost manufacturing. Unfortunately, one of the major drawbacks in these record cells is the presence of toxic volatile organic solvents (VOCs) in the electrolyte.

To overcome this problem, we have successfully tested eco-friendly reaction media such as Deep Eutectic Solvents (DESs), made of two or three safe and cheap components which are able to express hydrogen-bond interactions with each other to form an eutectic mixture with a melting point much lower than either of the individual components. DESs are simple and low-cost to synthesize, do not need purification, and they are usually biodegradable. One of the most common DES components, choline chloride (ChCl), is largely used as an additive for chicken feed. We tested both hydrophilic and hydrophobic DESs in DSSCs with promising results [1,2]. As a prototypical hydrophilic DES, we used ChCl/glycerol (1:2 mol mol–1) with 40% water jointly with an hydrophilic dye, and performed an extensive optimization of the device, including different co-adsorbents and TiO2 film thicknesses. Conversely, when using a hydrophobic DES made of menthol and acetic acid we chose a phenothiazine-based dye already studied in our group. DSSCs filled with DESs displayed a lower recombination resistance and a higher Voc when compared to cells filled with an electrolyte based on standard VOCs.

We then focused on DSSCs containing innovative sugar-based natural DES electrolytes, that is ChCl with different monosaccharides, sensitized with multi-branched phenothiazine dyes developed in our group, and characterized by the presence of an alkyl or a sugar substituent [3,4]. In particular, we systematically varied the dye (alkyl functionality vs. sugar moiety), the co-adsorbent (chenodeoxycholic acid vs. glucuronic acid), and the monosaccharide present in the DES. Overall, results are consistent with a cooperative interaction among all the components containing a sugar functionality leading to a performance boost.

____

[1] C. L. Boldrini, N. Manfredi, F. M. Perna, V. Trifiletti, V. Capriati, and A. Abbotto, Energy Technol. 2017, 5, 345-353. [2] C. L. Boldrini, N. Manfredi, F. M. Perna, V. Capriati, and A. Abbotto, Chem. Eur. J. 2018, 24, 17656-

17659. [3] N. Manfredi, B. Cecconi, V. Calabrese, A. Minotti, F. Peri, R. Ruffo, M. Monai, I. Romero-Ocana, T.

Montini, P. Fornasiero, and A. Abbotto, Chem. Commun. 2016, 52, 6977-6980.

[4] C. L. Boldrini, N. Manfredi, F. M. Perna, V. Capriati, A. Abbotto, ChemElectroChem 2020, 7, 1707-1712.


NICKEL CATALYZED TANDEM RING EXPANSION-CARBOXYLATION OF CYCLOBUTANONES WITH CO2

Lorenzo Lombardi*,a Giulio Bertuzzia and Marco Bandinia,b

a Dipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum – Università di Bologna, via Selmi 2, Bologna. b Consorzio CINMPIS, Università di Bologna, via Selmi 2, Bologna, Italy.


Carbon dioxide has emerged in the past decades as a green and abundant C1-synthon in organic chemistry. Nickel catalysis has emerged as a powerful tool for the carboxylation of various electrophiles under reductive conditions, capitalizing on the unique reactivity of Ni(I) species towards CO2. [1] The possibility of enhancing molecular complexity and, at the same time, introducing CO2 as a carboxylate precursor has recently emerged, giving rise to a number of tandem functionalization-carboxylation processes. [2] In this context, following our previous work reporting on a Nickel-catalyzed Heck coupling-carboxylation cascade [3], we present our latest results on a tandem ring expansion-carboxylation of cyclobutanones via C-C bond cleavage. [4] A specific class of particularly electron-rich bipyridine ligands, as well as the judicious choice of the proper additive, demonstrated crucial for the efficiency of this intriguing transformation.

____

[1] A. Tortajada, F. Juliá-Hernández, M. Börjesson, T. Moragas, R. Martin, Angew. Chem. Int. Ed. 2018, 57, 15948 – 15982. [2] X. Wang, Y. Liu, R. Martin, J. Am. Chem. Soc. 2015, 137, 6476−6479.

[3] A. Cerveri, R. Giovanelli, D. Sella, R. Pedrazzani, M. Monari, O. Nieto Faza, C. Silva López, M. Bandini, Chem. Eur. J. 2021, 27, 7657 –7662.

[4] Y.-L. Sun, X.-B. Wang, F.-N. Sun, Q.-Q. Chen, J. Cao, Z. Xu, L.-W. Xu, Angew. Chem. Int. Ed. 2019, 58, 6747 –6751.

Scheme 1: General representation of the direct arylation polymerization.


INFRARED IRRADIATION-ASSISTED PD-CATALYZED DIRECT (HETERO)ARYLATION POLYMERIZATION

Gianfranco Decandiaa,b, Gianluigi Albanoa, Pietro Cotugnoc, Angela Punzia, Gianluca M. Farinolaa*

aDipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70126 Bari, Italy

bIstituto per i Processi Chimico-Fisici CNR-IPCF, Dipartimento di Chimica, Via E. Orabona 4, 70126 Bari, Italy

aDipartimento di Biologia, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70126 Bari, Italy


Conjugated polymers are functional materials with a wide range of applications: from field-effect transistor to organic photovoltaics, from sensors to bioimaging materials. Generally, the polymerization process is catalyzed by a transition metal, typically Palladium, and it involves several organometallic reagents and aryl halides to form new carbon-carbon bonds. One of the major drawbacks is the preliminary preparation of the organometallic reagents, often air- and moisture-sensitive, expensive or even toxic[1]. Recently, direct arylation polymerization has attracted much attention as an environmentally friendly alternative to classic cross-couplings since it does not need organometallic compounds and does not form metallic salts as by-products. The main disadvantage is represented by the use of harmful solvents (e.g., DMF, DMA, toluene, etc.)[2], which, lately, have been replaced by more sustainable ones, such as 2-methyltetrahydrofuran and cyclopentyl methyl ether (CPME)[3].

In this work, the synthesis of a donor-acceptor polymer employed as active layer in plastic solar cell[4], composed of 4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b']dithiophene (BDT) as the electron-donating unit and 5-octyl-thieno[3,4-c]pyrrole-4,6-dione (TPD) as the electron-accepting unit has been performed. Polymerizations have been carried out using CPME as the solvent and an infrared (IR) lamp as the energy source: IR irradiation heating, actually, has proven to be a good alternative to conventional energy sources[5] and provides good yields and high molecular weights in just one hour reaction. ____

[1] R. D. Kimbrough. Environmental Health Perspectives 1976, 14, 51. [2] D. Prat; A. Wells; J. Hayler; H. Sneddon; C. R. Mcelroy; S. Abou-Shehada; P. J. Dunn. Green

Chemistry 2015, 18, 288.

[3] R. M. Pankow; L. Ye; N. S. Gobalasingham; N. Salami; S. Samal; B. C. Thompson. Polymer Chemistry 2018, 9, 3885.

[4] G. Marzano; F. Carulli; F. Babudri; A. Pellegrino; R. Po; S. Luzzati; G. M. Farinola. Journal of Materials Chemistry A 2016, 4, 17163.

[5] G. Albano; G. Decandia; M. A. M. Capozzi; N. Zappimbulso; A. Punzi; G. M. Farinola. ChemSusChem

2021, cssc. 202101070.


PEG-LIKE CHAINS MAKE NAPHTHALENE DIIMIDE-COPPER COMPLEXES MORE SUITABLE FOR PARALLEL G-QUADRUPLEXES.

Valentina Pirota, a,b,* Enrico Lunghi, a Alessandra Benassi, 1,2 Mauro Freccero 1 and Filippo Doria 1,*

a Department of Chemistry, University of Pavia, 27100 Pavia, Italy; b "G-Quadruplexes as INnovative ThERApeutiC Targets (G4-INTERACT), Universal Scientific Education and Research Network (USERN),

Pavia, Italy


G-quadruplex (G4) structures are high order secondary nucleic acid sequences rich in guanine, biologically relevant as innovative therapeutic targets, being involved in different key biological processes [1,2]. Among all, RNA G4s are characterized by a common parallel topology which prompts researchers to develop selective ligands by referencing this particular common feature [1]. In this context, we synthetized and characterized two new naphthalene diimides (NDIs) copper-complexes, HP2Cu and PE2Cu, inspired by promising results previously obtained with NDI-Cu-DETA ligand [3]. They have been differently functionalized with 2-(2-aminoethoxy)ethanol side-chains, to selectively drive redox-catalyzed activity towards parallel G4s (Figure 1) [4]. They both strongly coordinate Cu(II) at physiological pH (apparent constants of 16.30 and 17.95 for HP2Cu and PE2Cu respectively) and can highly stabilized TERRA RNA-G4 (until >25°C), a monomeric G4 that folds at telomeric level. Moreover, the peg-like chain of PE2Cu induces a drastic reorganization of the hybrid topology of hTel22, a DNA G4, towards a parallel one, strongly stabilizing it. The ROS-mediated oxidation (by hydroxyl radical and superoxide anion) was already proven on TERRA G4, resulting in a selective cleavage in the close proximity of the copper coordination sphere. These promising results lay a solid mainstay for the further development of selective functional NDI-ligands towards the parallel topology, the only possible one for RNA G4s, starting to answer to the notable need to exploit these targets for future innovative therapeutic approaches.

Figure 1. Chemical structures of NDI-Cu-DETA and of the novel HP2Cu and PE2Cu.

____

[1] Kharel, P. et al. Nucleic Acids Research 2020, 48 (2), 12534-12555.

[2] Spiegel, J. et al. Trends in Chemistry 2020, 2, 123-136. [3] Nadai, M. et al. J Am Chem Soc 2018, 140, 14528-14532.

[4] Zuffo, M. et al. Nucleic Acids Research 2018, 46 (19), e115.



A NEW CHIRAL AUXILIARY IN THE CERIUM-CATALYZED ENATIOSELECTIVE NAZAROV CICLIZATION/DECARBOXILATION

Dario Gentili,a Gabriele Lupidi,a Federico Vittorio Rossi,b Serena Gabrielli,a Marino Petrini,a Genny

Pastore,a Enrico Marcantonia

aSchool of Science and Technologies, Univerisity of Camerino, Via Sant’Agostino n.1 62032

bLaboratory Alchemia srl, Via San Faustino n. 68 20134, Milano


The synthesis of cyclic structures has always been a fascinating topic of organic synthesis, since the wide diffusion of these structures in many natural compounds and the countless biological properties that they offer. Among them, cyclopentenones are an important class of compound which possess many biological activities such as pesticidal (Jasmone), they could potentially be used against HIV (prostratin) and also cyclopentenone moiety is present in some hormone-type active molecules (i.e. prostagladins).[1]

Figure 1.

Different methods are available for the synthesis of this type of compounds, one of the most famous is the Nazarov cyclication, a 4π-electrocyclization of divinyl ketones in the presence of

Brøsnted or Lewis Acids.[2] Nowadays many scientists are focusing their effort to develop enantioselective Nazarov Reactions employing different types of catalyst.[3] During our studies of the Nazarov reaction on the Zerumbone, we observed that our cerium catalytic system under microwave irradiation on β-keto ester dienones provides cyclopentenone derivatives. In our conditions the Nazarov cyclization is followed by decarboxilation process of ester moiety,[4] and with substrates which possess chirality on alkoxy group, we developed an enantioselective sequential process to chiral substituted cyclopentenones.

Figure 2.

____ [1] L. A. Marsili, J. L. Pergemont, V. Gandon, M. J. Rivera, Org. Lett. 2018, 20, 7298–7203. [2] W. T. Spencer III, T. Vaidya, A. J. Frontier, Eur. J. Org. Chem. 2013, 18, 3621–3633.

[3] H. Zhang, Z. Lu, Org. Chem. Front. 2018, 5, 1763-1767. [4] S. Radja, M. Nakijama, M. Repjuing, Angew. Chem. Int. Ed. 2014, 53, 1–5.


DEVELOPMENT OF NEW SELENIUM-BASED STRATEGIES FOR THE SYNTHESIS OF HETEROCYCLES

Italo Franco Coelho Dias,a* Luana Bagnoli,a Claudio Santi, Eder Lenardão,b Francesca Marinia

a Department of Pharmaceutical Sciences, University of Perugia, Italy

b Center of Chemistry and Pharmaceutical Sciences, Federal University of Pelotas, Brazil


In recent years, vinyl selenones have been employed as starting material in several synthetic strategies for a simple and concise assembly of pharmaceutically privileged carbo- and heterocycles.1 Inspired by a previous work describing the synthesis of spirooxindole-pyrrolizines,2 we herein report new multicomponent reaction cascades for the synthesis of tetrahydroindolizines 4 and tetrahydropyrrolizines 6. In these processes azomethine ylides, generated in situ from the reaction between aldehydes 1 and pipecolic acid 3 or L-proline 5 react with the phenyl vinyl selenones 2 through 1,3-dipolar cycloaddition followed by elimination of the selenium moiety and, in the case of tetrahydroindolizines 4, by aromatization.

____

(1) Palomba, M.; Franco Coelho Dias, I.; Rosati, O.; Marini, F. Modern Synthetic Strategies with

Organoselenium Reagents: A Focus on Vinyl Selenones. Molecules 2021, 3148. https://doi.org/10.3390/molecules26113148.

(2) Palomba, M.; Monte, E. D.; Mambrini, A.; Bagnoli, L.; Santi, C.; Marini, F. A Three-Component [3 + 2]-Cycloaddition/Elimination Cascade for the Synthesis of Spirooxindole-Pyrrolizines. Org. Biomol. Chem.2021, 667–676. https://doi.org/10.1039/D0OB02321C.


SCALABLE PALLADIUM-CATALYSED NEGISHI CROSS-COUPLING REACTIONS BETWEEN ORGANOZINC REAGENTS AND (HETERO)ARYL

BROMIDES IN NONCONVENTIONAL SOLVENTS

Giuseppe Dilauro,a,* Filippo Perna,a Paola Vitale,a Antonio Salomone,b Vito Capriatia

aDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Consorzio C.I.N.M.P.I.S., Via E. Orabona, 4, I-70125 Bari, Italy.

bDipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Consorzio C.I.N.M.P.I.S., Via E. Orabona, 4, I-70125 Bari, Italy.


In spite of their enormous synthetic relevance, the use of polar organometallic reagents has been to date restricted to anhydrous conditions, inert atmospheres and low temperatures to avoid their fast decomposition and to control their reactivity. One of the most momentous challenge in organic synthesis is the replacement of harsh and volatile organic compounds by more environmentally responsible solvents.[1] Building upon our recent findings on the use of organometallics in unconventional reaction media [e.g., the so-called deep eutectic solvents (DESs), water],[2–7] in this Communication we report that a wide range of alkyl- and arylzinc reagents can undergo fast chemo- and regioselective cross-coupling reactions with functionalized (hetero)aryl bromides in the presence of a Pd catalyst, under mild reaction conditions and under air, using bulk water or DES as a privileged reaction medium, to afford the desired adducts in yields up to and over 98% (Figure 1).[8] The described protocol is scalable (up to 5g), and proceed in the absence of additional ligands, and with an easy recycling of both the DES or water and the catalyst. This methodology opens up new vistas in the perspective of the development of a sustainable organometallic chemistry in bio-inspired solvents.

Figure 1 Negishi coupling “on-water” or in DESs ____

[1] L. Cicco, G. Dilauro, F. M. Perna, P. Vitale, V. Capriati, Org. Biomol. Chem., 2021, 19, 2558. [2] G. Dilauro, M. Dell’Aera, P. Vitale, V. Capriati, F. M. Perna, Angew. Chem. Int. Ed., 2017, 56, 10200. [3]

G. Dilauro, S. Mata García, D. Tagarelli, P. Vitale, F. M. Perna, V. Capriati, ChemsSusChem 2018, 11, 3495. [4] S. Ghinato, G. Dilauro, F. M. Perna, V. Capriati, M. Blangetti, C. Prandi, Chem. Commun., 2019, 55, 7741. [5] F. Messa, G. Dilauro, F. M. Perna, P. Vitale, V. Capriati, A. Salomone, ChemCatChem 2020, 12, 1979. [6] G. Dilauro, A. F. Quivelli, P. Vitale,V. Capriati, F. M. Perna. Angew. Chem. Int. Ed. 2019, 58, 1799. [7] F. M. Perna, P. Vitale, V. Capriati, Curr. Opin. Green Sust. Chem. 2021, 30, 100487. [8] G. Dilauro, C. S. Azzollini, P. Vitale, A. Salomone, F. M. Perna, V. Capriati, Angew. Chem. Int. Ed. 2021, 60, 10632.


NANOSPONGES BASED ON SELF-ASSEMBLED STARFISH-SHAPED CUCURBIT[6]URILS FUNCTIONALIZED WITH IMIDAZOLIUM ARMS

Vincenzo Patamia,a,* Davide Gentile,a Roberto Fiorenza,b Vera Muccilli,b Placido G. Mineo,b Salvatore

Scirè b and Antonio Rescifinaa,c

a Dipartimento di Scienze del Farmaco e della Salute, Università di Catania, V.le A. Doria, 95125 – Catania, Italy, b Dipartimento di Scienze Chimiche, Università di Catania, V.le A. Doria, 95125 –

Catania, Italy, c Consorzio Interuniversitario Nazionale di ricerca in Metodologie e Processi Innovativi di Sintesi (CINMPS), Via E. Orabona, 4, Bari 70125, Italy.


New porous material based on the first supramolecular cucurbituril-based nanosponge was synthesized by the functionalization of cucurbit[6]uril with twelve 1-(2-bromoethyl)-3-methyl-1H-imidazol-3-ium arms (CB[6]-Funct12). The CB[6]-Funct12 was characterized by 1H- and 13C-NMR, FTIR, ESI-MS, and TGA analyses. The 3D-molecular model of CB[6]-Funct12, minimized at PM6-D3H4 semiempirical level of theory, shows a high symmetry and resembles a 12-armed Crossaster papposus starfish. The porous structure and the high adsorption capacity were demonstrated through surface area measurements and carbon dioxide adsorption. The new supramolecular sponge showed attractive properties as i) the highly porous structure that allowed the CO2 capture, ii) the possibility to reuse the adsorbed CO2 for organic synthesis, iii) the exciting thermal stability up to around 800 °C, with the potential use of this material in high temperatures reactions. Finally, the reuse of CO2 was successfully investigated in the carboxylation reaction of phenylacetylene [1].

___

[1] V. Patamia, D. Gentile, R. Fiorenza, V. Muccilli, P. G. Mineo, S. Scirè, A. Rescifina, Chem. Commun.

2021, 57, 3664-3667.


PHOTOCHROMIC TORSIONAL SWITCHES (PTS) TOWARDS LIGHT-RESPONSIVE / SELF-TUNING ORGANIC SEMICONDUCTORS

Anna Laura Sanna,a* Giuseppe Sforazzinia

a University of Cagliari, Department of Chemical and Geological Science, Cagliari, Italy


The geometrical arrangement of the p-orbitals in organic semiconductors plays a pivotal role for the optoelectronic properties of the resulting bulk materials.[1] Control over the π-bond geometry, e.g. the planarity, of an extended conjugated system offers the possibility to modulate the effective conjugation length of a π-system, thus, allowing for the tuning of optical and electronic properties.[1,2] In the present work we report on a novel molecular architecture, referred to as a ‘photochromic torsional switch’ (PTS),[3] consisting of a polymerizable bithiophene unit able to mechanically change its π-system planarity in response to a photochromic isomerization of a laterally attached azobenzene unit, as shown in Figure 1. The PTS architectures, proposed in this work, represent a new generation of photochromic dyes that can allow for the preparation of ‘light-responsive / self-tuning semiconductors’, thus paving the way for the development of devices with unprecedented optical and electronic properties.

Figure 1. PTS molecular architecture.

__

[1] S. Ko, E. T. Hoke, L. Pandey et al., J. Am. Chem. Soc., 2012, 134, 5222-5232 [2] R. Rieger, D. Beckmann, A. Mavrinskiy et al., Chem. Mater., 2010, 22, 5314-5218 [3] J. Maciejewski, A. Sobczuk, A. Claveau et al., Chem. Sci. 2016, 8, 361-365

Highly conjugated form Poorly conjugated form

S

S

NN

O

O

R

cisUV

S

NN

O

SR

o

transDark / Vis

rotation along thiophene-thiophene

bond

Planar

Twisted

R = H or OMe


EXPLORING THE POTENTIAL OF METALLATED STRAINED HETEROCYCLES: FLOW GENERATION, LITHIATION AND FUNCTIONALIZATION OF

1-AZABICYCLO[1.1.0]BUTANES

Pantaleo Musci,*a Timo von Keutz,b Leonardo Degennaro,a David Cantillo,b Christian Oliver Kappe,a Renzo Luisi.a

a Flow Chemistry and Microreactor Technology FLAME-Lab Department of Pharmacy – Drug Sciences University of Bari “A. Moro” Via E. Orabona 4, Bari, 70125 (Italy)

b Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz (Austria)


Modern medicinal chemistry is increasingly turning to unconventional structural motifs to optimize drug candidates. In this scenario, 1-azabicyclo[1.1.0]butanes (ABBs) are becoming appealing structural motifs that can be employed as click reagents or precursors of azetidines.1,2 Due to the shortage of tactics for the preparation and functionalization of nitrogen-bearing strained heterocycles, we developed a straightforward continuous flow process for one-pot generation, C3 lithiation and functionalization of ABB.3 With the aid of microfluidic technology, the process operates at higher temperatures and safer conditions if compared to batch mode, thanks to the capability of microreactors to handle metalated short-lived intermediates. A plethora of 3-substituted-1-azabicyclo[1.1.0]butanes have been prepared in continuous flow mode.

Figure 1. Microfluidic setup for the genesis, lithiation and trapping of 1-azabicyclo[1.1.0]butane and

strain release process.

Moreover, the possibility to install two different strained heterocycles on the same scaffold was explored, with spotlight on a new chemical space. Oxyranyl, oxetanyl and tetrahydrofuranyl ABBs were obtained in good yields and the strain release process led to intriguing 3,3-difunctionalized azetidines bearing an oxygenated heterocycle. ____

[1] A. Converso, P. L. Saaidi, K. B. Sharpless, M. G. Finn, J. Org. Chem. 2004, 69, 733. [2] a) J. M. Lopchuk, K. Fjelbye, Y. Kawamata, L. R. Malins, C.-M. Pan, R. Gianatassio, J. Wang, L.

Prieto, J. Bradow, T. A. Brandt, M. R. Collins, J. Elleraas, J. Ewanicki, W. Farrell, O. O. Fadeyi, G. M.

Gallego, J. J. Mousseau, R. Oliver, N. W. Sach, J. K. Smith, J. E. Spangler, H. Zhu, J. Zhu, P. S. Baran, J. Am. Chem. Soc. 2017, 139, 3209. b) R. Gianatassio, J. M. Lopchuk, J. Wang, C.-M. Pan, L. R. Malins,

L. Prieto, T. A. Brandt, M. R. Collins, G. M. Gallego, N. W. Sach, J. E. Spangler, H. Zhu, J. Zhu, P. S. Baran, Science 2016, 351, 241.

[3] P. Musci, T. von Keutz, F. Belaj, L. Degennaro, D. Cantillo, C.O. Kappe, R. Luisi. Angew. Chem. Int. Ed. 2021, 60, 6395.


A SELECTIVE FLUORESCENT LIGHT-UP APTAMERIC SYSTEM FOR DIAGNOSTICS AND THERANOSTICS

Ettore Napolitano,a,* Claudia Riccardi,a Domenica Musumeci,a,b Filippo Doria,c Rosa Gaglione,a Angela

Arciello,a Daniela Montesarchio,a

a Department of Chemical Sciences, University of Naples Federico II, Naples, Italy; b Institute of Biostructures and Bioimages, Naples, Italy; c Department of Chemistry, University of Pavia, Pavia, Italy


In order to develop effective theranostic systems targeting VEGF-A,1 we here focused on the interaction between the G-quadruplex (G4)-forming V7t12,3,4 aptamer and a novel fluorescent cyanine.5,6,7 V7t1 is a G-rich oligonucleotide aptamer that specifically recognizes VEGF-A, a cytokine overexpressed in cancer cells. The aim of this study is obtaining stable non-covalent complexes between the aptamer and the fluorescent probe that can be selectively internalized in cancer cells and thus recognize the target, giving a marked fluorescence light-up upon binding. Strong binding between the aptamer and the probe, ensured by cyanine stacking on terminal guanine tetrads of V7t1, could be a superior strategy for aptamer labelling over classical conjugation, based on covalent bonds between the aptamer and the probe. In fact, this system is intrinsically very simple, and does not require linkers which could alter the aptamer properties and particularly its folding. The interaction between the G4-forming aptamer and the fluorescent probe was studied using different biophysical techniques, i.e. circular dichroism, fluorescence spectroscopy and native gel electrophoresis. The cyanine-aptamer complex was tested on MCF-7 and HeLa cancer cells to evaluate the cell uptake, monitored by confocal microscopy, and in vitro anticancer efficacy. Our strategy shows promise for a useful combination of the therapeutic activity of V7t1 with a sensitive fluorescence-based detection of VEGF-A, identified as useful biomarker for early cancer diagnosis.

Figure 1. Selective fluorescence enhancement of the G4 dimer-cyanine complex upon VEGF interaction

____

[1] C.S. Melincovici, A.B. Bosca, S. Susman, M. Marginean, C Mihu, M. Istrate, I.M. Moldovan, A.L. Roman, C.M. Mihu, Rom. J. Morphol. Embryol. 2018, 59, 455

[2] Y. Nonaka, K. Sode, K. Ikebukuro, Molecules, 2010, 15, 215

[3] Y. Nonaka, W. Yoshida, K. Abe, S. Ferri, H. Schulze, T.T. Bachmann, K. Ikebukuro, Anal. Chem. 2013, 85, 1132

[4] F. Moccia, C. Riccardi, D. Musumeci, S. Leone, R. Oliva, L. Petraccone, D. Montesarchio, Nucleic Acids Res. 2019, 47, 8318

[5] X. Chen, J. Wang, G. Jiang, G. Zu, M. Liu, L. Zhou, R. Pei, RSC Adv. 2016, 6, 70117

[6] H. Ihmels, S. Jiang, M.M.A. Mahmoud, H. Schonherr, D. Wesner, I. Zamrik, Langmuir 2018, 34, 11866

[7] Y.Q. Wang, M.H. Hu, R.J. Guo, S.B. Chen, Z.S. Huang, J.H. Tan, 2018, 266, 187

V7t1 aptamer

Selective fluorescence

light-up upon G4

dimer recognition

VEGF recognition

and

induced G4

stabilization

Cyanineprobe


IR IRRADIATION-ASSISTED SOLVENT-FREE PALLADIUM-CATALYZED DIRECT AND DEHYDROGENATIVE (HETERO)ARYL-ARYL COUPLING

Gianluigi Albano,a Gianfranco Decandia,a,b Maria Annunziata M. Capozzi,a Angela Punzi,a Gianluca

Maria Farinola a

a Dipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70126 Bari, Italy; b Istituto per i Processi Chimico-Fisici CNR-IPCF, Via E. Orabona 4, 70126 Bari, Italy


Organic compounds based on the (hetero)aryl scaffolds have been extensively investigated in recent years. The development of efficient methods for the generation of (hetero)aryl-aryl bonds is the key step to produce these molecules. On one hand, the Pd-catalyzed direct arylation of (hetero)arenes opened new routes to (hetero)aryl-aryl bonds, replacing traditional transition metal-promoted cross-coupling reactions with organometallic systems.[1] On the other, the Pd-catalyzed dehydrogenative coupling of heteroarenes can be definitely included among reactions with the lowest economic and environmental impact, since they occur between two different (hetero)arenes without pre-activation of both coupling partners.[2] Although significant efforts have been made towards more sustainable conditions, including the use of recoverable catalysts and green solvents,[3] some issues still remain, such as the need of high temperatures and long reaction times. Non-conventional energy sources have recently earned increasing attention as valid alternative to the traditional thermal heating, due to their possibility of minimizing reaction time, improving product yields and also avoiding undesired by-products. In this context, infrared (IR) irradiation is very appealing: it is a highly efficient form of heating emitted from an inexpensive lamp, with high heat transfer rate, good heating homogeneity, low energy consumption and short heating time.[4] Thanks to these properties, IR irradiation could provide relevant advantages in organic synthesis.[5] However, its true potential is still unexplored, especially in the Palladium-catalyzed coupling chemistry. Here we have applied IR irradiation to Pd-catalyzed direct arylation of several (hetero)arenes (benzo[b]thiophene, thieno[3,4-c]pyrrole-4,6-dione, 1H-1,2,3-triazole, pentafluorobenzene) with aryl iodides, affording the corresponding coupling products in good yield and short time (from 15 minutes to 2 h).[6] Benefits of IR irradiation was then proved also in preliminary tests of Pd-catalyzed dehydrogenative coupling of polyfluoroarenes with thiophenes (Figure 1).

Figure 1. IR irradiation-assisted solvent-free Pd-catalyzed direct (a) and dehydrogenative

(b) (hetero)aryl-aryl coupling investigated in the present work. ____

[1] D. Alberico, M. E. Scott, M. Lautens, Chemical Reviews 2007, 107, 174-238. [2] X. Bugaut, F. Glorius, Angewandte Chemie International Edition 2011, 50, 7479-7481.

[3] T. Dalton, T. Faber, F. Glorius, ACS Central Science 2021, 7, 245-261. [4] R. Escobedo, R. Miranda, J. Martínez, International Journal of Molecular Sciences 2016, 17, 453.

[5] N. Zappimbulso, M. A. M. Capozzi, A. Porcheddu, G. M. Farinola, A. Punzi, ChemSusChem. 2021, 14, 1363-1369.

[8] [6] G. Albano, G. Decandia, M. A. M. Capozzi, N. Zappimbulso, A. Punzi, G. M. Farinola, ChemSusChem

2021, In Press, DOI: 10.1002/cssc.202101070.


GREEN AND SAFE HYDROGENATIONS IN DEEP EUTECTIC SOLVENTS

Serena Perrone,a,* Giuseppe Dilauro,a Francesco Messa,a Andrea N. Paparella,a Antonio Salomoneb

a Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Prov.le Lecce-Monteroni, 73100 Lecce, Italy; b Department of Chemistry, University of Bari "Aldo Moro", Via E. Orabona 4, 70125 Bari, Italy.


The reduction of nitrogen- and oxygen-containing functional groups, as well as the catalytic semihydrogenation of alkynes to access cis-alkenes, is of great importance in organic synthesis since reduction products are essential structural units in many natural products, pharmaceuticals, and agrochemicals [1]. Hydrogen is an explosive gas, its production needs extensive energy and generates a considerable amount of carbon dioxide. Therefore, the development of cost-effective reduction methods that use safe reagents, environmentally friendly solvents and prevent or minimize waste formation represents a challenge of great interest in sustainable chemistry. Continuing our interest in developing sustainable synthetic methodologies, herein, we describe an alternative and safe palladium-catalyzed hydrogenation reaction in Deep Eutectic Solvents (DESs, Figure 1), unconventional green solvents displaying low toxicity, high biodegradability, and renewability [2]. The use of aluminum powder in combination with water and a base, in DESs, results in an environmentally responsible and controlled in-situ formation of hydrogen [3]. Our optimized protocol was effective for the reduction of a wide range of molecules, containing C–C, C–N, C–O, N–O multiple bonds, as well as, changing the nature of DES components, the stereoselective semihydrogenation of alkynes to cis-alkenes was achieved, leading to the desired products in yield up to 99%. The simplicity, tunability, recyclability and the environmentally benign character of both catalytic system and DESs, offer numerous advantages over the currently available reduction methods, performed in toxic volatile organic solvents and employing external and pressurized dangerous H2 source.

Figure 1

____

[1] a) M. B. Smith, J. March, March’s Advanced Organic Chemistry, Wiley, Hoboken, NJ, 6th

edn, 2007; b) C. Oger, L. Balas, T. Durand, J.-M Galano, Chem. Rev. 2013, 133, 1313.

[2] a) Messa, S. Perrone, M. Capua, F. Tolomeo, L. Troisi, V. Capriati, A. Salomone, Chem.

Commun., 2018, 54, 8100; b) S. Perrone, M. Capua, F. Messa, A. Salomone, L. Troisi,

Tetrahedron, 2017, 73, 6193; c) M. Capua, S. Perrone, F. M. Perna, P. Vitale, L. Troisi, A.

Salomone, V. Capriati, Molecules, 2016, 21, 924.

[3] C. Schäfer, C. J. Ellstrom, H. Cho, B. Török, Green. Chem., 2017, 19, 1230.


PILLARARENE-BASED PDMAEMA/PES BLENDED POLYMERS: A NEW SUPRAMOLECULAR APPROACH TOWARDS ENVIRONMENTAL

REMEDIATION

Anna Notti,a Maria Rosaria Plutino,b Giulia Rando.a,*

a Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d’Alcontres 31, 98166, Messina, Italy; b Institute for the Study

of Nanostructured Materials, ISMN – CNR, Palermo, c/o Dep. ChiBioFarAm, University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy


In the last decades, new advanced filtration techniques have increasingly been developed for the removal of emerging pollutants, which are difficult to remediate using conventional wastewater treatment methods [1]. In this regard, nano- and ultrafiltration membranes represent a valuable solution for water purification. Polyethersulfone (PES) based membranes are already employed for the removal of different contaminants in ultrafiltration processes, thanks to its thermal and chemical stability. In particular, PES is also used as an embedding polymer for the production of new functional membranes to improve their hydrophilicity, porosity, surface properties and adsorption performances, by blending with other polymers, cross-linkers or nanofillers [2]. For this purpose, stimuli-responsive polymers like PDMAEMA, poly[2-(dimethylamino)ethylmethacrylate] [3], could be employed as a useful additive for the production of conjugated PES blends and therefore new advanced membranes. In this study it will be shown the production of new polymeric blends, obtained by the combination of PES with synthetized innovative smart polymers, featuring the responsiveness of PDMAEMA polymer and either the host-guest properties of the covalently linked pillararenes (Figure 1) [4]. The preparation of the A1 substituted pillar[5]arene derivative, suitable to be covalently inserted into the structure of the PDMAEMA polymer, will be described. New blended membranes and beads, developed for the selective separation of organic dyes in wastewater treatment, fabricated by a traditional non-solvent induced phase separation (NIPS) process, will be outlined. Finally, physical-chemical characterization together with adsorption tests of organic dyes with all the synthesized precursors and polymers will be reported.

Figure. Schematic representation of conjugated PES blends preparation.

____

[1] A. K.Badawi, K. Zaher, Journal of Water Process Engineering 2021, 40 , 1–11.

[2] T. A. Otitoju, A. L. Ahmad, B. S. Ooi, RSC Adv. 2018, 8, 1–19.

[3] M. Wei; Y. Gao; X. Li; M. J. Serpe, Polym. Chem. 2017, 8, 127–143. [4] T. Ogoshi, S. Kanai, S. Fujinami, T. A. Yamagishi, Y. Nakamoto, J. Am. Chem. Soc. 2008, 130,

5022–5023.


PALLADIUM SUPPORTED ON SILK FIBROIN AS A ROBUST AND VERSATILE COUPLING CATALYST

Giorgio Rizzoa, Gianluigi Albanoa, Gianluca M. Farinolaa*

a Dipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Via Edoardo Orabona 4, 70126, Bari, Italy


Silk Fibroin (SF) was the first ever reported organic support for catalysis, leading to the fascinating field of organocatalysis. It is known that SF is an efficient support for Palladium [1], Platinum [2] and Rhodium [3] in the hydrogenation reactions. A SF-Palladium catalyst for Suzuki-Miyaura cross-coupling reactions was prepared and optimized [4], often giving the desired pure biaryl as the only product, thus avoiding tedious purification steps and chromatography techniques. Pd/SF was also suitable for gram-scale reactions and for the synthesis of a key pharmaceutical intermediate. In the literature are known different biopolymers as supports in catalysis [5] but SF represents a valid alternative to these supports since the metal loading is very low, any additional ligand or toxic organic solvent are required, reactions can be completed in very short times, and they require only water and ethanol as solvents. It is worth emphasizing that Pd/SF showed an exceptionally high recyclability (up to 19 cycles) in a purely heterogeneous catalytic mechanism. The same catalyst was also successfully employed for the cross-coupling reaction of aryl chlorides, considered inert substrates in cross-coupling reactions [6], although harsher conditions were required. Moreover, Pd/SF was able to catalyze Ullmann homo-coupling reactions, with a strict reagent hindrance dependence, shedding light on the coordination chemistry of Pd and structural features on the catalyst.

Figure 1. Pd anchored on SF for different coupling reactions involving aryl halides. ____ [1] Y. Izumi, Nature 1959, 32, 932. [2] A. Akamatsu, Y. Izumi, S. Akabori, Nature 1961, 34, 1067. [3] A. Akamatsu, Y. Izumi, S. Akabori, Nature 1962, 35, 1706. [4] G. Rizzo, G. Albano, M. Lo Presti, A. Milella, F. G. Omenetto, G. M. Farinola, EurJOC 2020, 45, 6992. [5] A. Kumbhar, R. Salunkhe, Current Organic Chemistry 2015, 19, 2075. [6] A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41, 4176.

SF


TUNING THE SELF-ASSEMBLY OF CALIX[4]TUBE DERIVATIVES

Anna Notti,a Giuseppe Gattuso,a Marco Milone,a* Melchiorre F. Parisi,a Ilenia Pisagatti,a

Silvano Geremia,b

a Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, viale F. Stagno d’Alcontres 31, 98166 Messina; b Centro di Eccellenza di Biocristallografia,

Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, via L. Giorgieri 1, 34127 Trieste

*e-mail: [email protected]

Calix[4]tubes 1 are rod-shaped molecules consisting of two calix[4]arene units linked together, at their narrow rims, by four ethylene bridges [1]. The latter, together with the macrocyclic phenolic oxygen atoms, create a cryptand-like binding site that selectively encapsulates potassium ions [2]. So far, calix[4]tube derivatization has mainly dealt with the substitution pattern of the alkyl groups at the wide rim and, as a result, has not really tackled the design of specific building blocks for the assembly of supramolecular arrays. In order to shed light on the full supramolecular potential of this class of compounds we have synthesized octaamino- [3] and octatolylureacalix[4]tubes 2a and 2b, and we wish to report, in the course of this presentation, some preliminary studies on the fine-tuning of the self-assembly of these derivatives both in solution and in the solid state.

____

[1] P. Schmitt, P. D. Beer, M. G. B. Drew, P. D. Sheen, Angew. Chem. Int. Ed. Engl. 1997, 36, 1840–1842

[2] S. E. Matthews, P. D. Beer, In: Calixarenes in the Nanoworld, 2007, 109–133, Springer, Dordrecht, J. Vicens, J. Harrowfield, L. Baklouti (eds)

[3] M. Gaeta, E. Rodolico, M. E. Fragalà, A. Pappalardo, I. Pisagatti, G. Gattuso, A. Notti, M. F. Parisi,

R.Purrello, A. D’Urso, Molecules 2021, 26, 704


EXPLORING THE REACTIVITY OF 2-HYDROXY CYCLOBUTANONE DERIVATIVES

Francesco Secci

Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, 09042 Monserrato (Cagliari) ITALY


2-Hydroxycyclobutanone derivatives, represent a class of powerful tools and building blocks

for the development of new chemoselective and versatile synthetic methodologies.1 These

reactive four membered rings, are able to furnish a fair range of heterocyclic compounds such

as and indoles2 benzofurans3 or cyclopropane derivatives when reacted with appropriated

nucleophiles and catalysts.4 In the last years, our research group, rediscovered this molecular

scaffold, extending its reactivity portfolio and performing new transformations, also accessing

to a panel of bioactive compounds. Herein we report the state of the art, the results of our latest

investigations and the objectives achieved.

O

OH

R

O

R2NNH

O

R

O

SAr

RR'

SAr

ORR'

NH

O

R

____

[1] S. Porcu, A. Luridiana, A. Martis, A. Frongia, G. Sarais, D. J. Aitken, T. Boddaert, R. Guillot F. Secci,

Chem. Commun., 2018, 54, 13547 [2] F. Turnu, A. Luridiana, A. Cocco, S. Porcu, A. Frongia, G. Sarais, F. Secci, Org. Lett. 2019, 21, 7329.

[3] F. Secci, S. Porcu, A. Luridiana, A. Frongia, P. C. Ricci, Org. Biomol. Chem., 2020, 18, 3684 [4] S. Porcu, S. Demuro, A. Luridiana, A. Cocco, A. Frongia, D. J. Aitken, F. Charnay-Pouget, R. Guillot,

G. Sarais, F. Secci, Org. Lett. 2018, 20, 7699



SYNTHESIS OF PROTECTED SULFILIMINES FROM SULFINIMIDATE ESTERS

Michael Andresini,*a Mauro Spennacchio,a Leonardo Degennaro,a Renzo Luisia

aFlow Chemistry and Microreactor Technology FLAME-Lab, Department of Pharmacy-Drug Sciences, University of Bari “A. Moro”, Via E. Orabona 4, Bari 70125, Italy


Sulfilimines are highly valuable compounds in medicinal chemistry, mainly due to their use as precursors of the most popular sulfoximines.[1] The synthetic tactics for their preparation are generally limited to the imidation of thioethers [2], and to the derivatization of sulfinylamines.[3] Recently, we described the synthesis of sulfinimidate esters and sulfinamidines through nitrogen transfer to sulfenamides.[4] In this communication, we report for the first time, the reactivity of sulfinimidate esters as an electrophilic motif source. Several sulfinimidates have been transformed with Grignard and organolithium reagents through a formal nucleophilic substitution with the organometals, giving access to N-protected sulfilimines with remarkable structural variability. Moreover, the addition of Grignard reagents has been optimized using CPME as the green solvent and under air, targeting a sustainable process.

Figure. Synthesis of sulfinimidate esters from sulfenamides and their transformation into sulfilimines

____

[1] a) L. Degennaro, A. Tota, S. De Angelis, M. Andresini, C. Cardellicchio, M. A. Capozzi, G. Romanazzi, R. Luisi Eur. J. Org. Chem. 2017, 2017 (44), 6486–6490; b) M. Zenzola, R. Doran, L. Degennaro, R.

Luisi, J. A. Bull Angew. Chem. Int. Ed. 2016, 55 (25), 7203–7207; c) P. Mendonça Matos, W. Lewis, S.

P. Argent, J. C. Moore, R. Stockman Org. Lett. 2020, 22 (7), 2776–2780; d) E. L. Briggs, A. Tota, M. Colella, L. Degennaro, R. Luisi, J. A. Bull Angew. Chem. Int. Ed. 2019, 58 (40), 14303–14310.

[2] V. Bizet, C. M. M. Hendriks, C. Bolm Chem. Soc. Rev. 2015, 44 (11), 3378–3390. [3] Z.-X. Zhang, T. Q. Davies, M. C. Willis J. Am. Chem. Soc. 2019, 141 (33), 13022–13027.

[4] M. Andresini, M. Spennacchio, G. Romanazzi, F. Ciriaco, G. Clarkson, L. Degennaro, R. Luisi, Organic Letters 2020, 22, 7129.


ORGANIC DYE-BASED DYADS FOR THE PRODUCTION OF SOLAR FUELS

Cristina Decavoli,* Chiara Liliana Boldrini, Norberto Manfredi, Alessandro Abbotto

Dipartimento di Scienza dei Materiali, Università degli Studi di Milano-Bicocca, e Unità di Ricerca INSTM di Milano-Bicocca, via Roberto Cozzi 55, 20125 Milano, Italy.


Clean and affordable alternatives to fossil fuels are becoming crucial and many of them use the solar radiation as energy source. In this scenario, dye-sensitized photoelectrochemical cells (DS-PEC) play an important role. They can mimic the nature and obtain solar fuels like hydrogen and oxygen through sun-driven water splitting. The strategic center of the device is the photosensitizer which collects the solar radiation and converts it into the hole/electron couple. Organic dyes have been playing an emerging light harvesting role in photocatalysis and in DS-PEC due to their easy synthesis and tuning, low cost, and abundance of precursors [1]. The other important element in DS-PEC is the water oxidation catalyst (WOC) who fastens the water-splitting reaction. Unlike the dye, which in these devices is always chemically bonded to the surface of the electrode, the WOC, typically a ruthenium complex, can be dissolved in the solution where the electrode is immersed or anchored to its surface. In the first case, the efficiency of the device merely depends on the diffusion of the WOC to reach the electrode; while in the second case, the anchoring of WOC onto the surface reduces the quantity of dye that can be absorbed on it and therefore the collection of the incident light. Thus, a possible development of these systems is the synthesis of a single molecule, composed by the union of these two essential elements for a DS-PEC. In this way, it is possible to obtain the highest light harvesting and a faster charge transfer. Here, I will show you a way to connect these two elements in an integrated dye-catalyst dyad through the formation of a stable non-conjugated covalent bond between a specially designed organic dye and a ruthenium-based benchmark WOC. These dyads have been investigated in oxygen evolution through water-splitting, showing interesting faradaic efficiencies, thus triggering new perspectives for the design of efficient molecular dyads based on metal-free dyes for DS-PEC water splitting [2].

____ [1] a) B. Cecconi, N. Manfredi, T. Montini, P. Fornasiero, A. Abbotto, Eur. J. Org. Chem. 2016, 2016,

5194-5215; b) C. Decavoli, C. L. Boldrini, N. Manfredi, A. Abbotto, Eur. J. Inorg. Chem. 2020,

2020, 978-999.

[2] C. Decavoli, C. L. Boldrini, V. Trifiletti, S. Luong, O. Fenwick, N. Manfredi, A. Abbotto, RSC Adv. 2021, 11, 5311-5319.


STEPS IN THE JOURNEY TOWARD GREEN SOLID PHASE PEPTIDE SYNTHESIS (GSPPS)

Alessandra Tolomelli,* Walter Cabri, Lucia Ferrazzano, Giulia Martelli, Paolo Cantelmi, Chiara

Palladino, Dario Corbisiero, Alexia Mattellone, Tommaso Fantoni

P4Gi Lab – Department of Chemistry “Giacomo Ciamician” – Alma Mater Studiorum- University of Bologna, Via Selmi 2, 40126 Bologna, ITALY


The development of solid-phase peptide synthesis (SPPS) that originates from the seminal work of Bruce Merrifield back in the sixties, gave access to previously unavailable long peptides via iterative formation of amide bonds. Thanks to SPPS availability and its automation, polypeptides became a target for medicinal chemists and today more than 70 therapeutic peptides are on the market and about 100 are in clinical trial advanced stages.[1] The optimization of every single step of SPPS to increase process greenness has become fundamental, since achievement of complete conversion needs the use of reagents in excess, extensive washings and filtration of the solid support anchored growing peptide. The evaluation of alternative green and safe solvents and reagents in the development of a methodology including also recovery and recycle to decrease the process PMI, represents a step forward in the achievement of a really green SPPS[2,3].

____

[1] W. Cabri, P.Cantelmi, D. Corbisiero, T. Fantoni, L. Ferrazzano, G. Martelli, A. Mattellone A. Tolomelli,

Front. Mol. Biosc. 2021, 8, 565. [2] L. Ferrazzano, D. Corbisiero, G. Martelli, A. Tolomelli, A. Viola, A. Ricci and W. Cabri, ACS Sus. Chem. Eng., 2019, 7, 12867. [3] G. Martelli, P. Cantelmi, A. Tolomelli, D. Corbisiero, A. Mattellone, A. Ricci, T. Fantoni, W. Cabri,

F. Vacondio, F. Ferlenghi, M. Mor, L. Ferrazzano Green Chem., 2021,23, 4095.


MULTIFUNCTIONAL FLUORESCENT GRAPHENE-CYCLODEXTRIN

NANOPLATFORMS

Giulia Neri, a Angela Scala, a Antonino Mazzaglia, b Anna Piperno, a

a Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, Italy, b CNR-ISMN, Istituto per lo Studio dei

Materiali Nanostrutturati, V. le F. Stagno d’Alcontres 31, 98166, Messina, Italy


In the continuous attempt to reach high performing therapeutic tools, the attention was focused on the development of multimodal nanodevices combining the properties of therapeutic agents with the detectability of contrast ones, providing all-in-one nanomedicine tools. In the present work, we discuss the synthesis, the characterization, and the biological profile of a new fluorescent hybrid nanodevice based on the combination of cationic cyclodextrin and graphene (GCD@Ada-Rhod, see Figure 1). Additionally, the performance of GCD@Ada-Rhod as miRNA nanocarrier and its ability to modify the expression of cancer-correlated genes were investigated. [1-2]

Figure 1. Pictorial representation of GCD@Ada-Rhod nanoplatform.

____

[1] A. Piperno, A. Mazzaglia, A. Scala, R. Pennisi, R. Zagami, G. Neri, S. M. Torcasio, C. Rosmini, P. G.

Mineo, M. Potara, M. Focsan, S. Astilean, G. Guoying Zhou, M. T. Sciortino, ACS Appl. Mater. Interfaces 2019, 11, 46101.

[2] D. Caccamo, M. Currò, R. Ientile, E. AM Verderio, A. Scala, A. Mazzaglia, R. Pennisi, M. Musarra-Pizzo, R. Zagami, G. Neri, C. Rosmini, M. Potara, M. Focsan, S. Astilean, A Piperno, M. T. Sciortino, Int. J. Mol. Sci. 2020, 21, 4891.


NEW CATALYSTS IN GREEN CHEMISTRY

Enrico Cara,a Federico Cuccu,a Andrea Porcheddu,a Federico Casti,a*

Dipartimento di Scienze Chimiche e Geologiche, University of Cagliari, Monserrato, Sardinia, Italy.


In recent years, eco-sustainability has become an increasingly important concern, particularly its successful implementation in organic chemistry. To achieve this goal, green chemistry is destined for scientific research to solve the problems related to pollutants that are formed from organic reactions as waste products. This study will highlight those natural fibres, such as wool could work as catalysts for C-C bonds formation. [1]. Furthermore, we performed these reactions in solvents free conditions, fulfilling another principle of green chemistry.

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[1] Chang, H., Conversion of carbon dioxide into cyclic carbonates using wool powder-KI

as catalyst, Journal of CO₂ Utilization 24 (2018) 174–179


SYNTHESIS OF A THIO-ANALOGUE OF SIALYLLACTOSE TO TAGRET MUMPS VIRUS NEURAMINIDASE

Francesco Milanesi,a* Rosa Ester Forgione,b Cristina Di Carluccio,b Marie Kubota,c Ferran Fabregat

Nieto,b Antonio Molinaro,b Takao Hashiguchi,d Roberta Marchetti,b Alba Silipo,b Oscar Francesconi,a

a Department of Chemistry ‘’Ugo Schiff’’ and CERM,University of Florence, Polo Scientifico e Tecnologico, I-50019, Sesto Fiorentino, Firenze (Italy)

b Department of Chemical Sciences,University of Naples ‘’Federico II’’, Strada Comunale Cinthia 26, I-80126, Napoli (Italy)

c Department of Virology, Faculty of Medicine, Kyushy University, Fukuoka, 812-8582, Japan

d Laboratory of Medical Virology, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, 606-8507, Japan


Mumps virus is an infectious disease with high morbidity in non-immunized subjects. Despite the advent of an effective vaccine, the virus is still circulating, and it cause parotitis and other mild symptoms in children, instead, in adults, the virus can cause severe complications, like encephalitis and meningitis. Among all the glycoproteins expressed on the surface of the viral particle, the hemagglutinin neuraminidase (MuV-HN) has attracted the attention as potential target for the development of specific inhibitors. This protein is a specific sialic acid – binding lectin capable of recognizing and hydrolyzing terminal residues of sialic acid containing glycans and its elective ligand is constituted by Neu5Ac-α-2,3-Gal-β-1,4-Glc (Figure 1). To design a molecule capable of interfere in the recognition and hydrolysis processes, it is necessary to replace the O-glycosidic bond between Neu5Ac and Gal with a more stable one, without modifying the three-dimensional properties of the ligand. In this study we present the synthesis of a thio-analogue of Neu5Ac-α-2,3-Gal-β-1,4-Glc (Figure 1). The interaction between the analogue and MuV-HN has been characterized with a combination of NMR, fluorescence and computational studies.[1]

Figure 1: Design of the thio-analogue

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[1] Forgione R.E., Di Carluccio C., Milanesi F., Kubota M., Nieto F.F., Molinaro A., Hashiguchi T., Francesconi O., Mrchetti R., Silipo A., 2021, Submitted

AUTHOR INDEX

A

Abbotto A. OC4, OC22

Albano G. OC6, OC15, OC18

Andresini M. OC21

Arciello A. OC14

B

Bagnoli L. OC9

Bandini M. OC5

Bedini E. OC3

Benassi A. OC7

Bertuzzi G. OC5

Boldrini C. L. OC4, OC22

C

Cabri W. OC23

Cantelmi P. OC23

Cantillo D. OC13

Capozzi M. A. M. OC15

Capriati V. OC4, OC10

Cara E. OC25

Carreño M. C. PL2

Casti F. OC2, OC25

Colella M. KN2

Contini A. OC1

Corbisiero D. OC23

Cotugno P. OC6

Cuccu F. OC2, OC25

D

Decandia G. OC6, OC15

Decavoli C. OC22

Degennaro L. KN2, OC13, OC21

Di Carluccio C. OC26

Dilauro G. OC10, OC16

Doria F. OC7, OC14

F

Fabregat Nieto F. OC26

Fantoni T. OC23

Farinola G. M. OC6, OC15, OC18

Ferrazzano L. OC23

Fiorenza R. OC11

Forgione R. E. OC26

Francesconi O. OC26

Franco Coelho Dias I. OC9

Freccero M. OC7

G

Gabrielli S. OC8

Gaglione R. OC14

Gattuso G. OC19

Gentile D. OC11

Gentili D. OC8

Geremia S. OC19

H

Hashiguchi T. OC26

I

Iadonisi A. OC3

J

Jørgensen K. A. PL1

K

Kappe C. O. OC13

Kubota M. OC26

L

Langè V. KN5

Lenardão E. OC9

Lenci E. OC1

Lombardi L. OC5

Lombardo M. KN3

Luisi R. KN2, OC13, OC21

Lunghi E. OC7

Lupidi G. OC8

M

Manfredi N. OC4, OC22

Marcantoni E. OC8

Marchetti R. OC26

Marini F. OC9

Martelli G. OC23

Mattellone A. OC23

Mazzaglia A. OC24

Menichetti S. KN1

Messa F. OC16

Milanesi F. OC26

Mineo P. G. OC11

Montesarchio D. OC14

Molinaro A. OC26

Muccilli V. OC11

Musci P. KN2, OC13

Musumeci D. OC14

N

Napolitano E. OC14

Neri G. OC24

Notti A. OC17, OC19

O

Occhiato E. G. KN5

P

Palladino C. OC23

Paparella A. N. OC16

Parisi M. F. OC19

Pastore G. OC8

Patamia V. OC11

Perna F. M. OC4, OC10

Perrone S. OC16

Petrini M. OC8

Piperno A. OC24

Pirota V. OC7

Pisagatti I. OC19

Plutino M. R. OC17

Porcheddu A. OC2, OC25

Punzi A. OC6, OC15

R

Rando G. OC17

Rescifina A. OC11

Riccardi C. OC14

Rinaldi A. KN5

Rizzo G. OC18

Rossi F. V. OC8

S

Salomone A. OC10, OC16

Sanna A. L. OC12

Santi C. OC9

Scala A. OC24

Scarpi D. KN5

Scirè S. OC11

Secci F. OC20

Sforazzini G. OC12

Silipo A. OC26

Spennacchio M. OC21

T

Tolomelli A. OC23

Tota A. KN2

Trabocchi A. OC1

Traboni S. OC3

V

Vessella G. OC3

Vignolini S. KN4

Vitale P. OC10

von Keutz T. OC13

LIST OF PARTICIPANTS Albano Gianluigi – University of Bari

Andresini Michael – University of Bari

Bagnoli Luana – University of Perugia

Ballarotto Marco – University of Perugia

Bandini Marco – University of Bologna

Barattucci Anna – University of Messina

Boldrini Chiara Liliana – University of Milano-Bicocca

Bonaccorsi Paola – University of Messina

Brandi Alberto – University of Firenze

Capperucci Antonella– University of Firenze

Capriati Vito – University of Bari

Carreño Carmen – Madrid Autonomus University

Casti Federico – University of Cagliari

Cicco Luciana – University of Bari

Colella Marco – University of Bari

Cuccu Federico – University of Cagliari

D’Auria Maurizio – University of Basilicata

Davighi Maria Giulia – University of Firenze

Decandia Gianfranco – University of Bari

Decavoli Cristina – University of Milano-Bicocca

Dell’Aera Marzia – IC-CNR Bari

Di Maro Mattia – University of Firenze

Dilauro Giuseppe – University of Bari

Doria Filippo – University of Pavia

Francesconi Oscar – University of Firenze

Franco Coelho Dias Italo – University of Perugia

Gabriele Bartolo – University of Calabria

Gentili Dario – University of Camerino

Giofrè Salvatore – University of Messina

Goti Andrea – University of Firenze

Iadonisi Alfonso – University of Napoli Federico II

Jørgensen Karl Anker – University of Aarhus

Kohnke Franz H. – University di Messina

Lenci Elena – University of Firenze

Lombardi Lorenzo – University of Bologna

Lombardo Marco – University of Bologna

Lupi Michela – University of Firenze

Marini Francesca – University of Perugia

Menichetti Stefano – University of Firenze

Milanesi Francesco – University of Firenze

Milone Marco – University of Messina

Montesarchio Daniela – University of Napoli Federico II

Mordini Alessandro – University of Firenze

Musci Pantaleo – University of Bari

Musumeci Domenica – University of Napoli Federico II

Napolitano Ettore – University of Napoli Federico II

Nativi Cristina – University of Firenze

Neri Giulia – University of Messina

Notti Anna – University of Messina

Occhiato Ernesto Giovanni – University of Firenze

Parisi Melchiorre – University of Messina

Patamia Vincenzo – University of Catania

Peri Francesco – University of Milano-Bicocca

Perna Filippo – University of Bari

Perrone Serena – University of Salento

Petrini Marino – University of Camerino

Piperno Anna – University of Messina

Pirota Valentina – University of Pavia

Porcheddu Andrea – University of Cagliari

Pratesi Debora – University of Firenze

Pulpito Mara – University of Bari

Quivelli Andrea Francesca – University of Bari

Rando Giulia – University of Messina

Rescifina Antonio – University of Catania

Rinaldi Antonia – University of Firenze

Rizzo Giorgio – University of Bari

Rosati Ornelio – University of Perugia

Sancineto Luca – University of Perugia

Sanna Anna Laura – University of Cagliari

Santi Claudio – University of Perugia

Secci Francesco – University of Cagliari

Spennacchio Mauro – University of Bari

Temperini Andrea – University of Perugia

Tolomelli Alessandra – University of Bologna

Trabocchi Andrea – University of Firenze

Traboni Serena – University of Napoli Federico II

Vasa Kristian – University of Firenze

Viglianisi Caterina – University of Firenze

Vignolini Silvia – University of Cambridge

Vitale Paola – University of Bari

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september 7-8, 2021 department of chemical, biological

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