Supramolecular synthon identification in azelaic acid - Isonicotinamide cocrystal by solid-state NMR

Abstract

Supramolecular synthons are the smallest structural units that contain the information inherent in building large molecular assemblies. Here, we apply solid-state NMR methods for the identification of the synthon in a cocrystal of Azelaic acid [(CH sub(2)) sub(7)(COOH) sub(2)]- Isonicotinamide [C sub(6)H sub(6)N sub(2)O]. It is observed that the spin-lattice relaxation time of protons in the cocrystal is long, implying that the choice of experiments, particularly those that involve low-sensitivity nuclei, could be time consuming. It is noticed that the two dimensional sup(1)H double quantum (DQ) - sup(1)H single quantum (SQ) correlation experiment at very fast MAS (60 kHz) is able to provide information on proton-proton proximities that leads to an understanding of the synthon structure. Experiments such as the CP-Reverse CP and sup(1)H- sup(13)C HETCOR have been used to obtain spectral assignment which was additionally confirmed by first-principle GIPAW NMR chemical shift calculations. Present study indicates the basic unit to be a heterosynthon in Azelaic acid (AZA) - Isonicotinamide (INIC) cocrystal formed by two different modes of intermolecular connectivity, viz. acid-pyridine and acid-amide hydrogen bonding interactions. The presence of a CH...O type bond involving a hydrogen of INIC is also indicated from the observation of a larger chemical shift of the corresponding proton. The experimental protocol presented in this paper is expected to be a useful tool for the estimation of the basic structural arrangement of the synthons in a rapid fashion.