Unusual short intramolecular N-H•••H-C contact and weak intermolecular interactions in two N-(adamantan-1-yl)piperazine carbothioamides: Crystallography, quantum chemical study and in vitro urease inhibitory activity

被引：4

作者：

Al-Wahaibi, Lamya H. . ^{[1
]}

Mangaiyarkarasi, Sivashanmugam ^{[2
]}

Blacque, Olivier ^{[3
]}

Hassan, Hanan M. . ^{[4
]}

El-Emam, Ali . A. . ^{[5
]}

Percino, M. Judith ^{[6
]}

Thamotharan, Subbiah ^{[2
]}

机构：

[1] Princess Nourah bint Abdulrahman Univ, Coll Sci, Dept Chem, Riyadh 11671, Saudi Arabia

[2] SASTRA, Sch Chem & Biotechnol, Dept Bioinformat, Biomol Crystallog Lab, Thanjavur 613401, India

[3] Univ Zurich, Dept Chem, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[4] Delta Univ Sci & Technol, Fac Pharm, Dept Pharmacol & Biochem, Int Costal Rd, Mansoura 11152, Egypt

[5] Mansoura Univ, Fac Pharm, Dept Med Chem, Mansoura 35516, Egypt

[6] Benemerita Univ Autonoma Puebla, Un Polimeros & Elect Organ, Inst Ciencias, Val3 Ecocampus Valsequillo,Independencia O2 50, Puebla 72960, Mexico

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2023年 / 1291卷

关键词：

Adamantane cage; Urease inhibition; Noncovalent interactions; CLP-PIXEL energy; NCI plots; Hirshfeld surface analysis; CRYSTAL-STRUCTURE; HELICOBACTER-PYLORI; BASIS-SETS; COMPLEXES; THIOUREAS; ENERGIES; PROGRAM; DESIGN; SAR; HIV;

D O I：

10.1016/j.molstruc.2023.136052

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Crystal structures of two closely related N-(adamantan-1-yl)piperazine carbothioamides have been examined in detail using the Hirshfeld surface, fingerprint analysis, PIXEL energy for molecular dimers and noncovalent interaction (NCI) plots for intermolecular interactions. Both compounds namely, ethyl 4-[(adamantan-1-yl)car-bamothioyl]piperazine-1-carboxylate (1) and N-(adamantan-1-yl)-4-(2-methoxyphenyl)piperazine-1-carbo-thioamide (2) crystallized in the triclinic system with two crystallographically independent molecules in each case. X-ray analysis indicates that the piperazine ring in one of the molecules of 1 exhibits a boat and chair conformation in the other crystallographically independent molecule, while the corresponding ring in 2 adopts a chair conformation. An analysis of the fingerprint plots of the Hirshfeld surface provides a qualitative picture of how carboxylate and methoxyphenyl substituents contribute to stabilizing the crystal packing. Both structures show unusually short intramolecular N-H & BULL;& BULL;& BULL;H-C contact with some geometrical constraints in addition to intramolecular C-H & BULL;& BULL;& BULL;S interactions. The role of intramolecular N-H & BULL;& BULL;& BULL;H-C contact was established with potential energy surface scan and structural optimization. The CLP-PIXEL calculation gives the intermolecular interaction energies for the molecular dimers in these structures. Many dimers in 1 are stabilized by C-H & BULL;& BULL;& BULL;O/S/& pi; in-teractions, while others are stabilized by short H & BULL;& BULL;& BULL;H contacts. Intermolecular C-H & BULL;& BULL;& BULL;O interactions do not occur in 2. There are, however, intermolecular C-H & BULL;& BULL;& BULL;S/& pi; interactions and short H & BULL;& BULL;& BULL;H contacts in some dimers. We used NCI plots to identify the nature of the observed noncovalent interactions. Compared to the control inhibitor (thiourea), the title compounds have good inhibitory activity against urease in vitro. Molecular docking analysis identifies the key active site residues involved in intermolecular interactions between a small molecule and an enzyme.

引用

页数：13