Charge Density Analysis of 2-Pyridineformamide N(4)-Methylthiosemicarbazone (Z′ = 4): Role of an Enhanced N–H···S Thioureido Dimer

Abstract

Charge density distribution in 2-pyridineformamide N(4)-methylthiosemicarbazone (TSC4) has been determined using high-resolution X-ray diffraction data (100 K) and Hansen−Coppens multipole formalism. The results are interpreted in terms of Bader's quantum theory of atoms in molecules (QTAIM), electrostatic potential analysis, and theoretical calculations (CRYSTAL09). The study highlights the molecular dissimilarity at the electronic level. The N−H•••S interactions have a dominant role in stabilization of the TSC4 crystal structure. As each of the four S acceptors simultaneously engages in several interactions, the focus of study is on the lone pairs' electron density of these acceptors which is particularly able to adjust to the various spatial distributions of the interacting donor groups. The main structural feature of TSC4 is the formation of specific N−H•••S bonded dimers between two pairs of independent molecules. These dimers are the main building block in the crystal structure, and with the two additional N−H•••S contacts they represent a significant enhancement of a typical R 2 2 (8) dimer synthon which dominates among the thioureido-based crystal structures. Two TSC4 dimers are structurally very similar and exhibit considerable cohesive energy (−20.8 and −21.4 kcal/mol). This type of dimer is the only structural motif that is common for S acceptors of all four independent molecules.

X-ray Charge Density Study of the Drug Methimazole with Z′ = 2: Differences in the Electronic Structure of the Thiourea Core due to Crystal Packing Effects

“…Sulfur atom’s tendency to form a toroidal shape of deformation ED distribution was studied previously. , The authors showed that forming a torus around sulfur in thiourea derivatives is, at least partially, a result of charge redistribution due to the resonance effect. Interestingly, the position of torus was shown to be susceptible to polarization and subsequent inclination toward various strong intermolecular interactions …”

“…An advantage of this particular tactic is that the molecules are compared within a single experiment, which helps reduce systematic errors and ignore the inaccuracies of approximations during the multipole refinement and subsequent analysis of experimental electron density (ED). However, the charge density studies of compounds with Z ′ > 1 are quite scarce. − Besides, chemical equivalence constraints are sometimes imposed. A few detailed and thorough studies should be highlighted, which have focused on comparing the electronic features of independent molecules. ,, …”

“…However, the charge density studies of compounds with Z ′ > 1 are quite scarce. − Besides, chemical equivalence constraints are sometimes imposed. A few detailed and thorough studies should be highlighted, which have focused on comparing the electronic features of independent molecules. ,, …”

“…Furthermore, the electronic structure of such compounds is not less interesting. For example, in their series of experimental works, Bogdanović et al ,,, reported the sulfur atom’s ability to participate in various hydrogen bonds, including rather strong N–H···S interactions, and the consequent formation of a toroidal shape of deformation ED. As shown by the CSD analysis in work, more than 40% of compounds with the thiourea fragment contain a sulfur atom involved in four or more hydrogen bonds.…”

Relationship between the Crystal Structure and Tuberculostatic Activity of Some 2-Amidinothiosemicarbazone Derivatives of Pyridine

“… Overlay of molecules for analog structures from CSD (zwitterion form (YACFOY [ 39 ], WEXSUO [ 11 ], WEXSOI [ 11 ], SUZGUP [ 40 ], PASZEP [ 12 ], MEVNIK [ 41 ], BEWLOH [ 7 ], ADABIQ [ 42 ])—blue, neutral form (YAPJUV [ 43 ], XOTWUY01 [ 44 ], WOGGAC [ 44 ], WOGFUV [ 44 ], UYOSIM [ 45 ], MEMWUW [ 46 ], DIFROZ01 [ 47 ])—red). …”