We have carried out extensive computational analyses of the structure and bonding mechanism in trihalides DX⋅⋅⋅A− and the analogous hydrogen-bonded complexes DH⋅⋅⋅A− (D, X, A=F, Cl, Br, I) using relativistic density functional theory (DFT) at zeroth-order regular approximation ZORA-BP86/TZ2P. One purpose was to obtain a set of consistent data from which reliable trends in structure and stability can be inferred over a large range of systems. The main objective was to achieve a detailed understanding of the nature of halogen bonds, how they resemble, and also how they differ from, the better understood hydrogen bonds. Thus, we present an accurate physical model of the halogen bond based on quantitative Kohn–Sham molecular orbital (MO) theory, energy decomposition analyses (EDA) and Voronoi deformation density (VDD) analyses of the charge distribution. It appears that the halogen bond in DX⋅⋅⋅A− arises not only from classical electrostatic attraction but also receives substantial stabilization from HOMO–LUMO interactions between the lone pair of A− and the σ* orbital of D–X.

Halogen bonding vs. hydrogen bonding: A molecular orbital perspective

Synthesis, crystal structure, Hirshfeld surface, DFT calculations, Z-scan and nonlinear optical studies of novel flourinated hexahydropyrimidine

Searching for effective and selective anti‐inflammatory agents, our study involved designing and synthesizing new pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives 4–11. The structures of the synthesized derivatives were confirmed using different spectroscopic techniques. Virtual screening was achieved for the newly designed derivatives using in silico docking simulation inside the active sites of four proteins classified as two cyclooxygenases (COX)‐1 (PDB: 3KK6 and 4OIZ) and two COX‐2 (PBD: 1CX2 and 3LN1). Among them, six derivatives 4c, 5b, 6a, 7a, 7b, and 10b displayed the highest binding energy. These derivatives were evaluated for their in vitro COX‐1 and COX‐2 inhibitory activities and their selectivity indexes were calculated. Additionally, these derivatives displayed IC50 values ranging between 4.909 ± 0.25 and 57.53 ± 2.91 µM, and 3.289 ± 0.14 and 124 ± 5.32 µM, against COX‐1 and COX‐2, respectively. Furthermore, the tested derivatives were found to have selective inhibitory activity on the COX‐2 enzyme. Surprisingly, the two pyrazole derivatives 4c and 5b were found to be the most active, with IC50 values of 9.835 ± 0.50 and 4.909 ± 0.25 µM and 4.597 ± 0.20 and 3.289 ±  0.14 µM compared with meloxicam (1.879 ± 0.1 and 5.409 ±  0.23 µM) and celecoxib (5.439 ± 0.28 and 2.164 ± 0.09 µM) against COX‐1/‐2, respectively. Besides, two pyrazole derivatives, 4c and 5b, displayed a COX‐1/COX‐2 SI of 2.14 and 1.49. Computational techniques such as molecular docking, density function theory (DFT) calculation, and chemical absorption, distribution, metabolism, excretion, and toxicity evaluation were applied to explain the molecules’ binding mode, chemical nature, drug likeness, and toxicity prediction.

Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation

Structural, spectroscopic, quantum chemical, and molecular docking investigation of (E)-N'-(2,5-dimethoxybenzylidene)picolinohydrazide

Synthesis of thiophene derivatives: Substituent effect, Antioxidant activity, Cyclic voltammetry, Molecular Docking, DFT, and TD-DFT Calculations

Growth, structural, spectral, optical and thermal studies of a novel third-order nonlinear optical single crystal: Piperazine-1,4-diium bis(2, 4-dichlorobenzoate)

Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline): Synthesis, structural, DFT-computational, molecular docking, antibacterial, antioxidant, and anticancer studies

This study targets the construction of metalloporphyrin assemblies directed by fluorine-centered non-covalent interactions that can conveniently operate on a metallated tetrapyridylporphyrin system, which topologically resembles a wheel–axle duo We chose a series of Sn(axial-L)2-(5,10,15,20-tetrapyridylporphyrin) [Sn(L)2-TPyP, where L = fluorine-substituted benzoate moiety] complexes as our building units, which have only one fluorine atom on the benzoate moiety (compounds 1 and 2) but progressively increased to 2 (compound 3) and to 5 (compound 4) This stepwise augmentation also showed a concomitant increase in fluorine-based intermolecular interactions Four complexes with varying F : H ratios of 1 : 4 to 5 : 0 at the axle part of the molecule were structurally analyzed by single-crystal X-ray diffraction Fluorine-centered intermolecular interactions have been investigated and found to correlate with the number of fluorine atoms present at the axial benzoato-ligand of the wheel–axle duo The augmentation in the number of fluorine-centered interactions was theoretically supported by Hirshfeld surface analysis showing a steep increase from 11% (1/2) to 20% (3) to 39% (4) as a function of the degree of fluorine-substitution However, electrostatic potential surface (ESP) analysis clearly disproves the formation of σ-holes at fluorine atoms and thus vitiates their role as XB donors in these complexes The occurrence of such short-contacts as a result of the ‘Gulliver effect’ should not be ruled out in fluorine based crystal engineering attempts

J. Irshad Ahamed

Papers

Growth, structural, spectral, optical and thermal studies of a novel third-order nonlinear optical single crystal: Piperazine-1,4-diium bis(2, 4-dichlorobenzoate)

Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline): Synthesis, structural, DFT-computational, molecular docking, antibacterial, antioxidant, and anticancer studies

Nature of fluorine interactions in ‘wheel and axle’ topology based hexa-coordinated Sn(IV)-porphyrins: an experimental and theoretical analysis