Solid-State Versatility of the Molecular Salts/Cocrystals of 2-Chloro-4-nitrobenzoic Acid: A Case Study on Halogen Bonds

Abstract

2-Chloro-4-nitrobenzoic acid (2c4n) is an antiviral agent used for the treatment of HIV infection and to boost the immune response in immune deficiency diseases. In the present study, a series of eight molecular salts of 2c4n with pyridyl and benzoic acid derivatives have been synthesized by a crystal engineering approach and were characterized structurally by various spectroscopic, thermal, and X-ray diffraction techniques. Crystal structures of all synthesized molecular salts were determined by single-crystal X-ray diffraction techniques. In all synthesized molecular salts, the charge-assisted acid···pyridine/amine heterosynthon was found to be the primary supramolecular synthon. The synthesized salts, namely, 2c4n.g and 2c4n.h salts were found to be isostructural. Further, in the current work, the occurrence of weak halogen bonds in the presence of strong hydrogen bonds in the synthesized and in the reported molecular salts/cocrystals of 2c4n has been investigated. A detailed inspection of the crystal structures of salts/cocrystals of 2c4n was carried out to demonstrate the importance of halogen bonds in these crystal structures. It was found that 4 out of 8 synthesized molecular salts and 12 out of 24 reported molecular adducts of 2c4n were found to exhibit halogen bonds in their crystal structures. A similar kind of conformational change was observed for molecular salts exhibiting halogen bonds in their crystal structures; however, the conformations were found to be slightly different in other molecular salts. It was observed that two-point primary supramolecular synthon and stronger intramolecular Cl···O halogen bonds in the molecular adducts of 2c4n are found to be more susceptible to exhibit halogen bonds in their crystal structures. Halogen bond interactions played a vital role in the crystal stabilization of these molecular adducts.

Neutral and Ionic Form of (Benzylthio)Acetic Acid in Novel Aminopyrimidine Based Multi-Component Crystalline Phases

“…2). Such hydrogen-bonding geometry, comprising the carboxylic/carboxylate O atoms associated with the heterocyclic N atom and the 2-amino group, is characteristic of co-crystals [20,41] and salts [2,16] 2). Such hydrogen-bonding geometry, comprising the carboxylic/carboxylate O atoms associated with the heterocyclic N atom and the 2-amino group, is characteristic of co-crystals [20,41] and salts [2,16] hydrogen bond and the C13-H•••O2 interaction (Figure 5).…”

“…Such hydrogen-bonding geometry, comprising the carboxylic/carboxylate O atoms associated with the heterocyclic N atom and the 2-amino group, is characteristic of co-crystals [20,41] and salts [2,16] 2). Such hydrogen-bonding geometry, comprising the carboxylic/carboxylate O atoms associated with the heterocyclic N atom and the 2-amino group, is characteristic of co-crystals [20,41] and salts [2,16] hydrogen bond and the C13-H•••O2 interaction (Figure 5). Both synthons partake in the formation of two further ring motifs: homomeric ring R2 2 (8) formed by the N3-H•••N2 bond and a tetramer based upon a centrosymmetric R4 4 (10) motif based on C13-H•••O2 contact and the O2-H•••N1 hydrogen bond.…”

“…Supramolecular organic frameworks (SOFs), also known as multi-component crystalline solids/phases or multi-component molecular crystals, are a group of materials fabricated using supramolecular crystal engineering [1]. The supramolecular conglomerates are formed as a result of spontaneous intermolecular self-assembling achieved by creating various bunches of non-covalent interactions between the favorable functional groups that build up the molecules of organic co-partners [2]. The occurrence of the different non-covalent contacts, embracing classical and nonclassical H-bonds, electrostatic forces, π•••π stacking, π-cation and π-anion, lone pair-π attractions, and others, is a necessary factor to direct the molecular arrangement in the crystals [3].…”

“…various bunches of non-covalent interactions between the favorable functional groups t build up the molecules of organic co-partners [2]. The occurrence of the different n covalent contacts, embracing classical and nonclassical H-bonds, electrostatic forces, π stacking, π-cation and π-anion, lone pair-π attractions, and others, is a necessary facto direct the molecular arrangement in the crystals [3].…”

Supramolecular Assemblies of 3/4-Chlorobenzoic Acid and Amino-Chloropyridine Derivatives: Synthesis, X-ray Diffraction, DFT Calculations, and Biological Screening

“…Its effects against various ailments as medicine have been shown, and is a good Lewis base, causing its derivatives to have attractive ligands to accept protons and bind to metal centers [38][39][40][41]. Several halogenated derivatives of pyridine and organic acids have been well characterized, and their properties have been explored [42]. The multicomponent structure as a product can be efficiently predicted from Rule of 3.…”