Synthesis of BODIPY appended β-cyclodextrin sensors for improved understanding of molecular interactions

Gordon Rix, Sauradip Chaudhuri, Mindy Levine*

Department of Chemistry, University of Rhode Island, Kingston, RI 02881

Background

Acknowledgements

-Dr. Mindy Levine and the Levine research group

-This material is based upon work supported in part by

the National Science Foundation EPSCoR Cooperative

Agreement #EPS-1004057

-Special thanks to the office of Governor Raimondo for

the Gov. Gina M. Raimondo’s Summer Undergraduate

Research Fellowship award

References 1. Serio, N.; Roque, J.; Badwal, A.; Levine, M. Analyst 2015, 140, 7503-7507

2. Serio, N.; Moyano, D. F.; Rotello, V. M.; Levine, M. Chem. Commun. 2015, 51, 11615-

11618

3. Serio, N.; Prignano, L.; Peters, S.; Levine, M. Polycyclic Aromatic Compounds 2014, 34,

561-572

4. Serio, N.; Chanthalyma, C.; Prignano, L.; Levine, M. Supramol. Chem. 2014, 26, 714-

721

5. Serio, N.; Miller, K.; Levine, M. Chem. Commun. 2013, 49, 4821-4823

6. Mako, T.; Marks, P.; Cook, N.; Levine, M. Supramol. Chem. 2012, 24, 743-747

7. Hamai, S. J. Inclusion Phenom. Macrocyclic Chem. 2010, 67, 471-481

8. Fernandez-Rosas, J.; Pessego, M.; Cepeda-Plaza, M.; Basilio, N.; Parajo, M.; Rodriguez-

Dafonte, P.; Garcia-Rio, L. Org. Biomol. Chem. 2015, 13, 1213-1224

Fluorescence Applications

Past work has produced sensing systems that rely on

independent fluorophores and cyclodextrins in solution

Contingent upon formation of a ternary complex

between the analyte, fluorophore, and cyclodextrin

Emission

Analyte

Analyte

Reaction Scheme

β-CD β-CD β-CD

β-CD β-CD

n = 2, 5, 10

Preliminary evidence suggests synthesis of both

βCD-BD5 and βCD-BD10 was successful, while

synthesis of βCD-BD2 is still in progress

Conclusions and Future Work

Through attachment of fluorophore to the cyclodextrin,

efficient sensing requirements are reduced to a binary

complex between the analyte and the fluorophore-

appended cyclodextrin

BODIPY chosen for high quantum yield and low stokes shift

β-cyclodextrin chosen for ability to accommodate only one

guest molecule

Synthesis of higher order cyclodextrin

architectures may also yield more effective

sensing systems

Dimerization of cyclodextrin with fluorophore

attachment may allow for effective study of

molecular interactions including more than one

analyte

Structures reported herein as well as future

cyclodextrin architectures could constitute

valuable components in highly sensitive

detection of aromatic compounds

Statistical analysis is used

to achieve maximal

separation of aromatic

analytes based on energy

transfer

Data can then be used to

identify unknown analyte

1H NMR suggests attachment of BD5 and

BD10 to β-cyclodextrin proceeded as

expected, while attachment of BD2 may

have been unsuccessful

BD2 attachment reaction will be run again

at a larger scale

Concurrent work is exploring alternative

attachment sites

While secondary rim functionalization

provides the fluorophore with improved

cavity access, primary rim functionalization

may improve sensitivity and selectivity for

some analytes

β-cyclodextrin

βCD-BD10

BODIPY Fluorophore

βCD-BD5

βCD-BD2

β-cyclodextrin with fluorophore attached

at varying covalent tether lengths

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated

biphenyls (PCBs) are two types of carcinogenic aromatic pollutants

that can have profound impacts on marine environments, even at low

concentrations.

Our lab has worked on the development of detection methods that

depend on the transfer of energy from these compounds and other

analytes to fluorescent compounds, whose signal can then be

interpreted. However, this energy transfer can only occur efficiently

when both the fluorophore and the analyte are within close

proximity. This is accomplished with the use of a cavity-containing

cyclodextrin, which serves as a host for the two molecules.

By covalently attaching the fluorophore to the cyclodextrin, we hope

to reduce the requirements needed for efficient energy transfer, and

drastically improve the capabilities of toxicant sensing systems.

Depiction of a ternary complex between an

analyte, a fluorophore, and a cyclodextrin host

Analyte

Primary rim

Nonpolar cavity Secondary rim