Aljohani, Yousef S., Özşanlı, Hanifi, Aouad, Mohamed R., Rezki, Nadjet, Al-Kaff, Nadia S., Albelwe, Bayan L., Aggoune, Wahib, Argent, Stephen P., Coles, Nathan T.  ORCID: https://orcid.org/0000-0001-6190-9080, Kays, Deborah L. ORCID: https://orcid.org/0000-0002-4616-6001 and Said, Musa A.
2026.
Crystal structure, Hirshfeld surface analysis, DFT, NLO, and multi-target docking of a fluorinated 1,2,3-triazole diarylmethanol (4-FPh-TM).
Journal of Molecular Structure
1376
, 146830.
10.1016/j.molstruc.2026.146830
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Abstract
(1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)diphenylmethanol (4-FPh-TM), a novel fluorinated 1,2,3-triazole diarylmethanol, was synthesised in 93% yield via copper(I)-catalysed azide–alkyne cycloaddition (CuAAC) and characterised by multinuclear NMR (¹H, ¹³C, ¹⁹F), FT-IR, single-crystal XRD, Hirshfeld surface analysis, DFT calculations, and molecular docking. The compound crystallises in the monoclinic space group P2₁/n (Z = 4; R₁ = 0.0404). Hirshfeld surface analysis revealed that H···H (38.8%) and C···H/H···C (32.9%) dispersive contacts dominate crystal packing, with directional N···H/H···N (11.5%) and H···F/F···H (10.8%) interactions providing structural complementarity; a centrosymmetric O26 directs packing–H26···N15 R22(10) dimer (D···A = 2.856 Å). DFT calculations (B3LYP+D3) yielded a HOMO–LUMO gap of 5.20 eV, the widest in the analogous series, confirming high kinetic stability and a donor–acceptor electronic architecture. ELF/LOL analyses identified N15 as the dominant hydrogen-bond acceptor, and NCI-RDG mapping characterised the intramolecular non-covalent contact network. Non-linear optical analysis yielded a first-order hyperpolarisability β = 24.48 × 10⁻³¹ esu (∼6.6 × that of urea), thereby establishing molecular NLO activity. Molecular docking against acetylcholinesterase (AChE; PDB: 1EVE), butyrylcholinesterase (BuChE; PDB: 4DJU), and monoamine oxidase B (MAO-B; PDB: 2V5Z), benchmarked against donepezil, rivastigmine, and selegiline, showed competitive or superior non-covalent binding affinities at all three targets. ADMET profiling confirmed Lipinski compliance and blood–brain barrier permeability, supporting 4-FPh-TM as a multi-target directed ligand candidate for further in vitro evaluation.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Chemistry |
| Additional Information: | RRS Policy applied License information from Publisher: LICENSE 1: Title: This article is under embargo with an end date yet to be finalised. |
| Publisher: | Elsevier |
| ISSN: | 0022-2860 |
| Date of First Compliant Deposit: | 11 September 2026 |
| Date of Acceptance: | 13 June 2026 |
| Last Modified: | 11 Sep 2026 09:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/187875 |
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