Characterization, molecular modelling, and thermochemistry of proton-transfer adducts derived from interaction of piperidine and morpholine with two strong organic acceptors
2026· Bulletin of the Chemical Society of Ethiopia· Vol 40· 0 citations
Abstract
This study investigates the formation and properties of three proton-transfer complexes: piperidine-picric acid (PIP–PA), piperidine-7,7,8,8-tetracyanoquinodimethane (PIP–TCNQ), and morpholine-picric acid (MOR–PA). Utilizing piperidine and morpholine as electron donors, picric acid (PA) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as strong organic electron acceptors, this research employs both experimental and computational methods to analyze their electronic structures and stability. Experimentally, equimolar quantities of the donor and acceptor were reacted in chloroform; the resulting precipitates were purified and recrystallized to yield colored crystals. Composition was confirmed via CHN elemental analysis, UV/Vis spectroscopy, and FT-IR spectroscopy, while thermal stability and phase transition behavior were assessed using a Uni-melt capillary melting point apparatus. Theoretically, quantum-chemical calculations were performed using the SE-PM6 method in the Spartan software package. The results indicate linear correlations between experimental melting points and calculated formation enthalpies, heat capacities, dipole moments, and absolute hardness values. Ultimately, this integration of experimental and theoretical approaches elucidates the proton-transfer interactions involved, providing essential insights for the development of advanced organic electronics, such as sensors and high-efficiency solar cells.
KEY WORDS: Piperidine, Morpholine, Picric acid, TCNQ, Proton-transfer complex, Experimental approach, Theoretical approach
Bull. Chem. Soc. Ethiop. 2026, 40(11), 2305-2317
DOI: https://dx.doi.org/10.4314/bcse.v40i11.2
Two new thiosemicarbazone-type Schiff base ligands, [L1] and [L2], were synthesized in high purity by refluxing (7 h, 70–75 °C, glacial acetic acid catalyst) an ethanolic solution of N-phenylhydrazinecarbothioamide with benzil and benzoin, respectively, and were subsequently reacted with hydrated CoCl2 and NiCl2 (2:1 ligand:metal molar ratio, 4 h reflux at 70–75 °C) to give the corresponding octahedral Co(II) and Ni(II) chelates. The ligands and their metal complexes were characterized by melting point, yield, elemental composition, FT-IR, UV-Visible, 1H- and 13C-NMR, mass spectrometry, magnetic susceptibility, thermogravimetric analysis (TGA), and frontier molecular orbital (HOMO/LUMO) calculations. The spectral evidence supports coordination of the metal ions through the azomethine nitrogen and thioamide sulfur/nitrogen donor sites, giving predominantly octahedral geometries for the hydrated Co(II) and Ni(II) chelates, in agreement with their measured magnetic moments. Molecular docking of L1 and L2 against the human enzyme Phosphodiesterase 3A (PDE3A) was performed to evaluate their potential as enzyme-binding scaffolds, and the resulting binding energies, hydrogen-bonding interactions and docking scores are reported and discussed in the context of the reported pharmacological relevance of PDE3A.
Nabaa N. Mohammed, Wurood A. Jaafar, Noha Ali Hadi· Open Access Research Journal...· 0 citations
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para
-substituted benzaldehydes. The products were obtained in a yield range of 70–95% and characterized by Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance (
1
H NMR) spectroscopy. Docking studies were performed against carbonic anhydrase models 2H4N and 7PP9, and the ranking was refined using Prime molecular mechanics/generalized Born surface area (MM-GBSA) analysis. The most favorable MM-GBSA values were observed for AT5 against 2H4N (–46.79 kcal/mol) and AT3 against 7PP9 (–50.56 kcal/mol). QikProp and SwissADME profiling suggested generally acceptable molecular weights, lipophilicity, solubility, and predicted oral absorption. A 200 ns Desmond molecular dynamics simulation of the AT3-2H4N complex showed retention of the modeled binding pose with ligand conformational fluctuations during the trajectory. Overall, these findings identify coumarin-hydrazide-hydrazone derivatives as computationally prioritized scaffolds that require biochemical CA inhibition and cellular validation before any anticancer conclusion can be drawn.
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Promoted by the well-established, valuable biological activity of thiophene-based hybrids, the study displayed the synthesis of two series of thiophene-pyrazole hybrids,
7a-c
and thiophene-pyridine hybrids
9a-c,
via
reacting arylhydrazone with halogenated reagents and nucleophilic addition of cyanoacetamide to the arylidene-malononitrile, respectively. The chemical structure of the produced hybrids was elucidated using reliable spectroscopic techniques, including Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR), and Mass spectra (MS). The density functional theory (DFT) modeling of the delivered conjugates disclosed comparable non-planar configurations and frontier molecular orbital (FMO) constructions, in which the benzoate junction and oxo-thienyl moiety performed as donor (highest occupied molecular orbital; HOMO) and acceptor (lowest unoccupied molecular orbital; LUMO) portions, respectively. Furthermore, the antimicrobial activity of the manufactured hybrids was evaluated, and analog
7a
exhibited outstanding activity against both bacterial strains and C. albicans, with large inhibition zones (IZ = 41-43 mm). Meanwhile, the cytotoxicity efficacy of the synthesized derivatives was assessed against human breast cancer (MCF-7), normal kidney epithelial (Vero), and the normal cells (WI-38) cell lines. The series
7a-c
was more active in general than the other conjugates; for example, derivative
7a
was very selective towards MCF-7 (IC
50
= 14.39±0.26 μM). Furthermore, the hybrid’s inhibitory effect on the bacterial topoisomerases IV and
DNA gyrase B
was evaluated, where hybrid
7a
presented the greatest action (IC
50
= 12.09±0.31 and 0.43±0.12 μM), respectively. Moreover, molecular docking performed against bacterial
DNA gyrase B
revealed that analogues
7a-c
and
9a-c
exhibited superior bindings; analogue
9c
demonstrated the strongest binding energy (-7.9520 kcal/mol), proposing improved target arrangement. Finally, the Swiss absorption, distribution, metabolism and excretion (ADME) analysis highlighted the pharmacokinetic properties of the synthesized thiophene hybrids. Analogues with low molecular weight,
4
and
5
, exhibited optimal solubility and absorption, while bulkier analogues
6
,
7a-c,
and
9a-c
presented lower solubility due to increased topological polar surface area (TPSA) and lipophilicity.
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Abstract A novel trifluoromethyl-pyrimidine derivative, 5‑chloro‑2‑((2‑methyl‑6‑(trifluoromethyl) pyrimidin‑4‑yl)oxy)aniline, was synthesized and structurally confirmed through 1H NMR, 13C NMR, FT-IR and high-resolution mass spectrometry (HRMS). The density functional theory (DFT)/B3LYP method with a 6-311 + G (2d,p) basis set was adopted to execute the title compound’s molecular structure conformational analysis. The calculated optimal structure was consistent with the crystal structure obtained from X-ray single-crystal diffraction. Furthermore, calculations of the frontier molecular orbital and molecular electrostatic potential surface maps were carried out to acquire more information. In addition, the title compound exhibited promising antifungal efficacy, highlighting its potential as a new fungicide candidate.
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