Cahit Orek

Synthesis, experimental, theoretical characterization and biological activities of 4-ethyl-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione.

This work presents the characterization of 4-ethyl-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione (III) by quantum chemical calculations and spectral techniques. The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of III in the ground state have been calculated using the density functional method (B3LYP) with the 6-31G(d) basis set. The calculated results show that the optimized geometry can well reproduce the crystal structure, and the theoretical vibrational frequencies and chemical shift values show good agreement with experimental values. To determine conformational flexibility, the molecular energy profile of the title compound was obtained by DFT calculations with respect to the selected torsion angle, which was varied from -180° to +180° in steps of 10°. The energetic behavior of III in solvent media was examined using the B3LYP method with the 6-31G(d) basis set by applying the Onsager and the polarizable continuum model (PCM). The predicted nonlinear optical properties of III are greater than ones of urea. In addition, DFT calculations of molecular electrostatic potentials and frontier molecular orbitals of III were carried out at the B3LYP/6-31G(d) level of theory. The title compound was screened for antibacterial, antifungal and antioxidant activities.

Investigation of acetylcholinesterase and mammalian DNA topoisomerases, carbonic anhydrase inhibition profiles, and cytotoxic activity of novel bis(α-aminoalkyl)phosphinic acid derivatives against human breast cancer

The aim of this study was to evaluate biologically active novel molecules having potentials to be drugs by their antitumor properties and by activities of apoptotic caspase and topoisomerase. Following syntheses of novel eight bis(α‐aminoalkyl)phosphinic acid derivatives (4a–h) as a result of array of reactions, compounds were evaluated by cytotoxic effects in vitro on human breast cancer (MCF‐7) and normal endothelial (HUVEC) cell lines. All phosphinic acid derivatives were effective for cytotoxicity on both MCF‐7 and HUVEC lines, while 4c, 4e, and 4f compounds were found significantly more effective. For the evaluation of antitumor properties of compounds in a highly sensitive method, their effects on inhibiting topoisomerases I and II were investigated. Also, some of the bis(α‐aminoalkyl)phosphinic acid derivatives (4a, 4e–h) showed nice inhibitory action against acetylcholinesterase and human carbonic anhydrase isoforms I and II.

6-Phenyl-3-(4-pyridyl)-1,2,4-triazolo-[3,4-b][1,3,4]thiadiazole: synthesis, experimental, theoretical characterization and biological activities.

The molecular geometry, vibrational frequencies, and gauge including atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the title compound in the ground state have been calculated using the Hartree-Fock (HF) and density functional theory (DFT) methods with 6-31G(d) basis sets, and compared with the experimental data. The calculated results show that the optimized geometries can well reproduce the crystal structural parameters and the theoretical vibrational frequencies, and (1)H and (13)C NMR chemical shift values show good agreement with experimental data. To determine conformational flexibility, molecular energy profile of the title compound was obtained by HF/6-31G(d) and (DFT/B3LYP) calculations with respect to selected degree of torsional freedom, which was varied from -180° to +180° in steps of 10°. The energetic behavior of the title compound in solvent media was examined using the B3LYP method with the 6-31G(d) basis set by applying the Onsager and the polarizable continuum model (PCM). The results obtained with these methods reveal that the PCM method provided more stable structure than Onsagers method. The title compound has been tested in vitro for biological effects.

N-cyclohexyl-2-[5-(4-pyridyl)-4-(p-tolyl)-4H-1,2,4-triazol-3-ylsulfanyl]-acetamide dihydrate: synthesis, experimental, theoretical characterization and biological activities.

The triazol compound N-cyclohexyl-2-[5-(4-pyridyl)-4-(p-tolyl)-4H-1,2,4-triazol-3-ylsulfanyl]-acetamide dihydrate has been synthesized and characterized by (1)H NMR, (13)C NMR, IR, and X-ray single-crystal determination. The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of III in the ground state have been calculated using the density functional method (B3LYP) with the 6-31G(d) basis set. The calculated results show that the optimized geometry can well reproduce the crystal structure, and the theoretical vibrational frequencies and chemical shift values show good agreement with experimental values. The energetic behavior of III in solvent media was examined using the B3LYP method with the 6-31G(d) basis set by applying the Onsager and the polarizable continuum model (PCM). The predicted nonlinear optical properties of III are greater than ones of urea. In addition, DFT calculations of molecular electrostatic potentials, frontier molecular orbitals and thermodynamic properties of III were carried out at the B3LYP/6-31G(d) level of theory. The title compound was screened for antibacterial, antifungal and antioxidant activities.

4-Allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione: synthesis, experimental and theoretical characterization.

The title molecule, 4-allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione (C(10)H(10)N(4)S), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic space group is P2(1)/c, a=8.006(5)Å, b=15.363(5)Å, c=8.936(5)Å, β=104.441(5)° and V=1064.4(10)Å(3), F(000)=456, D(x)=1.362 g/cm(3). In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) (1)H and (13)C chemical shift values of the title compound in the ground state have been calculated using the Hartree-Fock (HF) and density functional method (DFT/B3LYP) with 6-31G(d) basis set. To determine conformational flexibility, molecular energy profile of the title compound was obtained by HF/6-31G(d) and (DFT/B3LYP) calculations with respect to selected degree of torsional freedom, which was varied from -180° to +180° in steps of 10°. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), and several thermodynamic properties were performed by the HF and DFT methods.

Synthesis and In-Vitro Antimicrobial Activity of Novel Aminophosphinic Acids Containing Cyclobutane and 1,3-Thiazole

Abstract The compounds {[4-(3-methyl-3-aryl(mesityl-phenyl-tetralino)cyclobutyl)-1,3-thiazol-2-yl]amino}(aryl)methyl-phosphinic acids 2a–l were prepared by condensation of 2-amino-4-(3-aryl(mesityl-phenyl-tetralino)-3-methylcyclobutyl) thiazoles 1a–c with various aromatic aldehydes and hypophosphorous acid through a one-pot reaction. The characterizations of these compounds were obtained by elemental analyses, infrared (IR) spectra, and 1H, 13C, and 31P NMR (nuclear magnetic resonance) techniques. The synthesized compounds were tested in vitro against one Gram-positive and two Gram-negative bacterial strains, one mycobacterial strain, and a fungus Candida albicans. Compound 2f showed significant activity against Staphylococcus aureus, whereas the others had no remarkable activity on this strain. Compound 2g was found to be more active than the others against Mycobacterium fortuitum at an MIC (minimum inhibitory concentration) value of 32 μg/mL. The antibacterial and antifungal activities of 2a–l were also compared with various standard drugs. [Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Biological Activities. Table S1. Figures S1–S6.] GRAPHICAL ABSTRACT

Synthesis and in vitro antioxidant evaluation of new bis(α-aminoalkyl)phosphinic acid derivatives

GRAPHICAL ABSTRACT ABSTRACT Diamines were added to arylaldehydes in ethanol, which resulted in corresponding diimines. Novel bis-1-aminophosphinic acid compounds were synthesized through the interaction of diimines and hypophosphorous acid. The new compounds were characterized by elemental analyses, FT-IR and 1H, 13C and 31P NMR techniques. The in vitro antioxidant activity of the newly synthesized compounds were measured and found to exhibit significantly higher antioxidant activity than the standard.

Ab initio studies of the Rg–NO+(X1Σ+) van der Waals complexes (Rg = He, Ne, Ar, Kr, and Xe)

We used the explicitly correlated variant of the coupled clusters method with single, double, and noniterative triple excitations [CCSD(T)-F12] to compute two-dimensional potential energy surfaces of van der Waals complexes formed by rare gas atoms (Rg) and NO(+)(X(1)Σ(+)) cations. We used the correlation-consistent, triple-zeta (cc-pVTZ-F12) atomic basis sets, and for Kr and Xe rare gases, we employed corresponding pseudopotential cc-pVTZ-PP-F12 atomic basis sets. These basis sets were additionally augmented with mid-bond functions. The complexes are all of skewed T-shape type with Rg atom being closer to the N-side. Using analytical representation of the potentials, we have estimated zero-point energy corrected dissociation energies from anharmonic calculations with BOUND program and also from the harmonic approximation. The binding energies increase with the polarization of the Rg atom in series from He to Xe and are 196 cm(-1), 360 cm(-1), 1024 cm(-1), 1434 cm(-1), and 2141 cm(-1), respectively. Their corresponding dissociation energies are 132 cm(-1), 300 cm(-1), 927 cm(-1), 1320 cm(-1), and 1994 cm(-1) for the complexes with He to Xe, respectively. We find good agreement with previous theoretical and experimental results. The harmonic vibrational frequencies were calculated for the bending and stretching modes of the Rg-NO(+) complexes.

Synthesis and Characterization of Novel Chiral (1R,2R)-1,2-Bis[5-(Aminomethylphospinic Acid)-1,3,4-Thiadiazol-2-YL]Ethane-1,2-Diols

Abstract (1R,2R)-1,2-bis[5-(arylideneamino)-1,3,4-thiadiazol-2-yl]ethane-1,2-diol (2a–d) were synthesized by using appropriate aldehydes and (1R,2R)-1,2-bis(5-amino-1,3,4-thiadiazol-2-yl)ethane-1,2-diol (1) as a starting compound. Then, the phosphinic acid component (3a–d) were obtained from (2a–d) and hypophosporus acid. In addition, the structures of the novel chiral compounds (2a–d) and (3a–d) were confirmed by elemental analyses, IR, 1H-NMR, 13C-NMR, and 31P-NMR spectra. 1H NMR and 13C NMR spectra for 1, 2a, and 3a (Figures S1–S6) are available online in the Supplemental Materials. GRAPHICAL ABSTRACT