Supramolecular Self-Assembly Mediated by Multiple Hydrogen Bonds and the Importance of C-S···N Chalcogen Bonds in N'-(Adamantan-2-ylidene)hydrazide Derivatives

Lamya H Al-Wahaibi; Karthick Vishal Asokan; Nora H Al-Shaalan; Samar S Tawfik; Hanan M Hassan; Ali A El-Emam; M Judith Percino; Subbiah Thamotharan

doi:10.1021/acsomega.2c00159

Supramolecular Self-Assembly Mediated by Multiple Hydrogen Bonds and the Importance of C-S···N Chalcogen Bonds in N'-(Adamantan-2-ylidene)hydrazide Derivatives

ACS Omega. 2022 Mar 17;7(12):10608-10621. doi: 10.1021/acsomega.2c00159. eCollection 2022 Mar 29.

Authors

Lamya H Al-Wahaibi¹, Karthick Vishal Asokan², Nora H Al-Shaalan¹, Samar S Tawfik³, Hanan M Hassan⁴, Ali A El-Emam⁵, M Judith Percino⁶, Subbiah Thamotharan²

Affiliations

¹ Department of Chemistry, College of Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
² Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, India.
³ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
⁴ Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, International Costal Road, Gamasa City, Mansoura 11152, Egypt.
⁵ Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
⁶ Unidad de Polímeros y Electrónica Orgánica, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Val3-Ecocampus Valsequillo, Independencia O2 Sur 50, San Pedro Zacachimalpa, Puebla 72960, Mexico.

Abstract

The present article comprehensively examines six N'-(adamantan-2-ylidene)hydrazide derivatives using the Hirshfeld surface analysis, PIXEL energy for molecular dimers, lattice energies for crystal packing, and topological analysis for intramolecular and intermolecular interactions. The crystal structure of one of the N'-(adamantan-2-ylidene)hydrazide derivatives, namely, N'-(adamantan-2-ylidene)-5-bromothiophene-2-carbohydrazide 1, C₁₅H₁₇N₂OSBr, has been determined and analyzed in detail along with five closely related structures. The molecular conformation of 1 is locked by an intramolecular C-S···N chalcogen bond as found in one of its closely related structure, namely, N'-(adamantan-2-ylidene)thiophene-2-carbohydrazide. Furthermore, a detailed potential energy surface scan analysis has been performed to highlight the importance of a chalcogen bond. Two of these compounds possess syn-orientation for amide units, whereas the corresponding moiety exhibits anti-conformations in the remaining four structures. The Hirshfeld surface and its decomposed fingerprint plots provide a qualitative picture of acyl substituent effects on the intermolecular interactions toward crystal packing of these six structures. Intermolecular interaction energies for dimers observed in these structures calculated by density functional theory (B97D3/def2-TZVP) and PIXEL (MP2/6-31G**) methods are comparable. This study also identifies that multiple hydrogen bonds, including N/C-H···O/N and C-H···π interactions, are collectively responsible for a self-assembled synthon. The nature and strength of these interactions have been studied using atoms in molecule topological analysis. The in vitro antiproliferative activity of compound 1 was assessed against five human tumor cell lines and showed marked antiproliferative activity.