Diazole-based powdered cocrystal featuring a helical hydrogen-bonded network: Structure determination from PXRD, solid-state NMR and computer modeling

resumo

We present the structure of a new equimolar 1:1 cocrystal formed by 3,5-d imethy1-1H-pyrazole (dmpz) and 4,5-dimethy1-1H-imidazole (dmim), determined by means of powder X-ray diffraction data combined with solid-state NMR that provided insight into topological details of hydrogen bonding connectivities and weak interactions such as C-H center dot center dot center dot pi contacts. The use of various 1D/2D C-13, N-15 and H-1 high-resolution solid-state NMR techniques provided structural insight on local length scales revealing internuclear proximities and relative orientations between the dmim and dmpz molecular building blocks of the studied cocrystal. Molecular modeling and DFT calculations were also employed to generate meaningful structures. INT refinement was able to decrease the figure of merit R(F-2) from similar to 11% (PXRD only) to 5.4%. An attempt was made to rationalize the role of N-H center dot center dot center dot N and C-H center dot center dot center dot pi contacts in stabilizing the reported cocrystal. For this purpose four imidazole derivatives with distinct placement of methyl substituents were reacted with dmpz to understand the effect of methylation in blocking or enabling certain intermolecular contacts. Only one imidazole derivative (dmim) was able to incorporate into the dmpz trimeric motif thus resulting in a cocrystal, which contains both hydrophobic (methyl groups) and hydrophilic components that self-assemble to form an atypical ID network of helicoiclal hydrogen bonded pattern, featuring structural similarities with alpha-helix arrangements in proteins. The 1:1 dmpz...dmim compound I is the first example of a cocrystal formed by two different azoles. (C) 2014 Elsevier Inc. All rights reserved.

palavras-chave

CRYSTAL-STRUCTURE PREDICTION; AB-INITIO CALCULATIONS; X-RAY-DIFFRACTION; PI-INTERACTIONS; H-1-NMR SPECTROSCOPY; MAS NMR; AROMATIC NANOCHANNELS; POLARIZATION TRANSFER; QUADRUPLE PROTON; CO-CRYSTALS

categoria

Chemistry; Physics; Spectroscopy

autores

Sardo, M; Santos, SM; Babaryk, AA; Lopez, C; Alkorta, I; Elguero, J; Claramunt, RM; Mafra, L

Grupos

G1 - Materiais Porosos e Nanossistemas
G6 - Materiais Virtuais e Inteligência Artificial

Projectos

Development of High-Resolution 1h Solid-State NMR Methods and Applications on Materials and Molecules of Biological Interest (PTDC/QUI-QUI/100998/2008)

Polymorphism in pharmaceuticals: new insights from NMR Crystallography (EXPL/QEQ-QFI/2078/2013)

Centre for Research in Ceramics and Composite Materials - CICECO (LA0011: 2011-2012) (PEst-C/CTM/LA0011/2011)

agradecimentos

We thank FCT, QREN, COMPETE, and EU for financial support and postdoc Grants for M.S. (SFRH/BPD/65978/2009), S.M.S. (SFRH/BPD/64752/2009) and A. A. B. (sponsored by the FCT project PTDC/QUIQUI/100998/2008). The Portuguese NMR Network (RNRMN) is acknowledged for granting access to the 18.8T NMR Bruker spectrometer at ITQB. FCT is also acknowledged for funding R&D Projects PTDC/QUI-QUI/100998/2008, EXPL/QEQ-QFI/2078/2013 (COMPETE: COMP-01-0124-FEDER-041966) and PEst-C/CTM/LA0011/2011. Thanks are also given to the Ministerio de Economia y Competitividad of Spain (Projects CTQ2009-13129-C02-02 and CTQ2010-16122) and the Comunidad Autonoma de Madrid (Project MADRISOLAR2, ref. S2009/PPQ-1533). LM thanks FCT for the awarded development Grant (IF/01401/2013).