Unveiling structural features, chemical reactivity, and bioactivity of a newly synthesized purine derivative through crystallography and computational approaches
Abad, Nadeem, Buhlak, Shafeek, Hajji, Melek, Saffour, Sana, Akachar, Jihane, Kesgun, Yunus, Al-Ghulikah, Hanan, Hanashalshahaby, Essam, Turkez, Hasan, Mardinoglu, Adil
We introduce the synthesis and characterization of a novel purine derivative, 2-amino-6-chloro-N,N-diphenyl7H-purine-7-carboxamide. X-ray crystallography was utilized to elucidate its molecular and crystal structure. A comprehensive crystal packing analysis uncovered a network of diverse intermolecular interactions, including classical and unconventional hydrogen bonding. Remarkably, a unique halogen & sdot;& sdot;& sdot;pi (C-Cl & sdot;& sdot;& sdot;pi(ring)) interaction was identified and theoretically analyzed within a multi-approach quantum mechanics (QM) framework, revealing its lone-pair & ctdot;pi (n ->pi*) nature. Furthermore, insights into the electronic and chemical reactivity properties are provided by means of Conceptual Density Functional Theory (CDFT) at wB97X-D/aug-cc-pVTZ level. The compound's drug-likeness, pharmacokinetics, and toxicology profiles are assessed using ADMETlab 2.0. Finally, molecular docking simulations were conducted to evaluate its bioactivity as a potential cyclooxygenase-2 (COX-2) inhibitor. This study significantly advances our understanding of purine structure and reactivity, offering valuable insights for the development of targeted purine-based COX-2 inhibitors and anticancer therapeutics.
- Dergi
- JOURNAL OF MOLECULAR STRUCTURE
- Yıl
- 2024
- Cilt
- 1311
- ISSN
- 0022-2860
- eISSN
- 1872-8014
- DOI
- 10.1016/j.molstruc.2024.138400
- WoS UID
- WOS:001233606400001