Part of the Special Issue “Facets of Polymorphism in Crystals.”

Solid-State Polymorphic Transition and Solvent-Free Self-Assemblyin the Growth of Organic Crystalline Microfibers

Daniela. S. Tsekova,*,† Beatriu Escuder,‡ and Juan F. Miravet*,‡

Department of Organic Chemistry, UniVersity of Chemical Technology and Metallurgy,8 St. Kliment Ohridski BouleVard, 1756 Sofia, Bulgaria, and Department of Inorganic and OrganicChemistry, UniVersitat Jaume I, 12071-Castellon, Spain

ReceiVed August 7, 2007; ReVised Manuscript ReceiVed NoVember 15, 2007

ABSTRACT: The study of the crystalline xerogel formed by a newly synthesized L-valine and pyridine containing low-molecular-weightgelator reveals a polymorphic transition above 225 °C that is followed by the formation of microfibers. The habitus of the fibers grownremains stable upon cooling. Microscopic observations lead to the suggestion that after the polymorphic transition, the fibers are formed bya sublimation process. Results obtained reveal the intrinsic tendency of this compound to self-assemble anisotropically in fibers that permitthe preparation of organic crystalline micro- and nanofibers in solvent-free conditions.

Self-assembly is a very useful tool for the synthesis of structureslarger than molecules with sizes from nanometers to micrometers.1

In this area of research and in the context of the work carried outin nanoscience, a challenging goal is the preparation of functionalobjects that present well-defined shapes and in which at least onedimension lies in the range of 1 to ca. 100 nm.2 In particular,investigation of self-assembled fibers and fibrils is the focus of veryactive research that includes, for example, the study of diseasesrelated to protein aggregation and the development of new materialssuch as supramolecular gels.3 These materials have potentialapplications in fields that include tissue engineering, template forinorganic nanofibers and electrooptical materials among others.Recently, we have studied supramolecular gels formed by nicotinoyland isonicotinoyl derivatives related to compound 1 (see Scheme1). The presence of a pyridine moiety in this type of moleculesprovides the basis for the formation of pH-responsive gels and forthe incorporation of catalytic metals on to the fibers.4

Here, we want to report that compound 1 forms, under dry,solvent-free conditions, well defined microscopic fibers afterexperiencing a solid-state polymorphic transition (see Figure 1).Polymorphism refers to the formation of different crystal latticesretaining the same chemical composition. The study of polymor-phism in molecular crystals is a very active field, with a mainchallenge being to reliably predict and explain the emergence ofdifferent polymorphic forms.5 Polymorphism is quite common inthe formation of self-assembled fibrilar networks.6 In many cases,analysis by X-ray powder diffraction (XRPD) of the xerogelobtained after evaporation of the solvent shows that these systemsare microcrystalline and that different polymorphs can be obtained,for example, using different conditions of solvent polarity ortemperature.

The study of the self-assembly of compound 1 has revealed thatit is a low-molecular-weight gelator capable of forming gels in someorganic solvents and in water (Figure 2a). This process is the resultof the formation of self-assembled fibrillar networks upon coolingthe corresponding solutions.3 It has been also observed that,depending on the solvent, concentration, or cooling rate, compound1 can produce precipitates that are shown under the microscope to

contain spherulites (images b and c, Figure 2). In all the cases,XRPD analysis reveals that the solid materials obtained after solventevaporation are microcrystalline and their diffraction patterncorresponds to what is called in the following discussion polymorph1r. We have found that upon heating this material above 225 °C,

* Corresponding author. E-mail: d_tsekova@uctm.edu (D.S.T.); miravet@uji.es(J.F.M.). Phone: 935928163418 (D.S.T.).

† University of Chemical Technology and Metallurgy.‡ Universitat Jaume I.

Scheme 1. Chemical Structure of Compound 1 andTransitions between 1r and 1�

Figure 1. Scanning electron microscopy (SEM) images of some stepsof transformation during the heating of 1: (a) compound 1 (polymorph1r) powdered; (b) initial stages of fibril growth above 225 °C(polymorph 1�); (c) fibers grown after prolonged heating, before meltingat ∼270 °C (polymorph 1�); (d) material obtained after meltingcompound 1 and cooling to room temperature (polymorph 1�).

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a solid-state polymorphic transition takes place that results in amaterial, polymorph 1�, with a diffraction pattern that differs clearlyfrom that of the starting material (see Figure 3). Crystallographicanalysis (WIN-INDEX) of the data obtained from XRPD patternssuggest several possible solutions for the elementary crystal cell,all of which correspond to a triclinic crystal lattice for bothpolymorphic forms. Differential scanning calorimetry data (see theSupporting Information) revealed two endothermic peaks corre-sponding to the polymorphic transition at 225 °C (1r-1�,solid–solid) and melting at 276 °C.

Remarkably, it is observed that following this polymorphictransition, a very noticeable change in the microscopic aspect ofthe material is produced progressively at temperatures above 225°C (see Figure 1). For example, upon heating a dry powder of 1r,after the polymorphic transition, filament-shaped crystals are firstproduced that evolve after several minutes to long fibers withdiameters that range from approximately 1 µm to 200 nm and

present the diffraction pattern of the 1� form. These fibers are stableuntil the melting temperature, 276 °C. Upon solidification of themelt, a microfibrilar solid is obtained that corresponds to polymorph1� (see also Supporting Information).

A possible chemical transformation of the material upon thermaltreatment could be rejected taking account of the fact that 1H NMRspectrum of 1� in deuterated DMSO was identical to that of 1r.Additionally, thermogravimetric analysis revealed no weight dif-ference when the polymorphic transition takes place. Furthermore,we have found that after solubilization of the 1� form, gels orspherulites are produced in the appropriate conditions of concentra-tion and temperature that correspond in all cases to polymorph 1r.

It is worth mentioning that IR spectra of both polymorphic solids(see Figure 4 and the Supporting Information) show small differ-ences that must reflect their different packing modes. For example,a shoulder on the CdO vibrations was observed at ca. 1700 cmfor 1�, which suggests that the H-bonding pattern differs from thatfound in 1r. Additional differences in the IR spectra affect thefingerprint region below 1500 cm-1. As a matter of fact, H-bondingis most likely the driving force for the aggregation of these type ofmolecules, and models for aggregation with extended conformationsthat present multiple H-bonds have been proposed by for relatedmolecules4b,7 (a possible model obtained by molecular mechanicscalculations for the structure of the aggregates formed by 1 is shownin the Supporting Information).

It is also significant that solid-state circular dichroism (CD)spectra of 1r and 1� polymorphs show differences (see Figure 5).This suggests that the polymorphic transition is accompanied by achange in the relative spatial orientation of the chromophoric units.

A detailed mechanistic explanation of solid-state transitionsrepresents in general a challenge.8 In this case, it can be thoughtthat first the material experiences a polymorphic transition and thena sublimation process that produces the fibers takes place progres-sively. This is supported by the fact that the observed transformationto fibrils requires prolonged heating above the polymorphictransition temperature for at least several minutes and thatvolatilization of part of the material is observed under themicroscope.

Figure 2. SEM photographs of the crystalline habitus of the solidsobtained from compound 1 (a-c) formed in solutions, correspondingto 1r: (a) xerogel obtained in dioxane, (b) spherulites obtained inchloroform, (c) structure of a spherulite at a higher magnification. (d-f)Needles corresponding to 1�, obtained after the polymorphic transitionupon heating 1r.

Figure 3. X-ray powder difractogram of 1r (bottom) and 1� (top).

Figure 4. X-ray IR spectra of polymorphs 1r and 1�. (see the Supporting Information for more details).

Figure 5. CD spectra of KBr pellets (0.25% w/w) of 1r (solid line)and 1� (dotted line).

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As mentioned before, the compound presented here pertains tothe family of the so-called low-molecular-weight gelators (LMWG)which generally tend to form anisotropic 1D aggregates that resultin fiberlike objects.3 The described results can be rationalized ifone considers that kinetically favorable crystalline long fibers areformed from the supersaturated solutions that result either in gelor spherulite formation. Upon thermal treatment, the crystallinearrangement found in 1r changes to give place to the fiberlikepolymorphic material 1�, which is found to be stable in atemperature range from 25 °C to the melting point.

As a conclusion, we believe that the presented results providean example of formation of well-defined micro- and nanocrystalsfollowing a solid-state polymorphic transition. This finding couldexemplify a new alternative to the most common self-assemblyprocesses performed in solutions and used for the preparation of avariety of nanoshaped objects. Probably, dry self-assembly proce-dures could be considered advantageous both from technical andenvironmental points of view and they are related to active researchin solvent-free procedures for organic and organometallic synthesis.9

It is worth mentioning that because compound 1 is a low-molecular-weight gelator, its capability of producing fibrilar networks insolution is manifested in the absence of solvent. It also has to benoted that polymorph 1� is obtained only after a solid-statepolymorphic transition from 1r. Up to the moment, all the solidsobtained from solutions afforded 1r.

Acknowledgment. We thank Prof. N. Avramova (Sofia Uni-versity) and Prof. A. Mitsulov (UCTM -Sofia) for their commentson the DSC data and XRPD measurements. We also thank for thefunding provided by UCTM (Research Contract 10113), GeneralitatValenciana (GV06/322), and Ministerio de Educación y Cienciaof Spain (CTQ2006–14984). Technical assistance from the SCIC(Universitat Jaume I) is acknowledged.

Supporting Information Available: Experimental details of theprocedures and techniques used; spectroscopic characterization ofcompound 1; IR spectra of 1r and 1�; CD spectra of 1r and 1� insolutions; DSC graph of the polymorphic transition; additional opticalmicroscopy images of 1r and 1�, XRPD peaks listing and molecularmodel of 1 (PDF). This information is available free of charge via theInternet at http: //pubs.acs.org.

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7324–7328. (b) Molecular Gels: Materials with Self-Assembled FibrillarNetworks; Weiss, R. G., Terech, P., Eds.; Kluwer Academic: Dordrecht,The Netherlands, 2005. (c) Sangeetha, N. M.; Maitra, U. Chem. Soc.ReV. 2005, 821–836.

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