Synthesis, spectroscopic characterizations and DFT studies on the metal complexes of azathioprine immunosuppressive drug

ABSTRACT. A complex of the immunosuppressive drug azathioprine with Cr(II), Mn(II), Fe(II), Zn(II), Cu(II), Ni(II), and Co(II) were synthesized and characterized through spectroscopic and thermal studies. The infrared spectra show the coordination of azathioprine via N(9) to the metal, also, the range around 640–650 cm−1 remains unchanged in the complexes, indicating the possibility that the ether group may not be involved in the binding. Thermogravimetric analysis (TG), thermogravimetric derivational analysis (DTG), and differential thermogravimetric analysis (DTA) have been studied in the temperature range from 0 °C to 1000 °C. The study of pyrolysis showed that all complexes decompose in more than one step and that the final decomposition product is metal oxide. The DFT (density functional theory) with B3LYP/6-31G++ level of theory was used to study the optimized geometry, HOMO→LUMO energy gap, and molecular electrostatic potential map of azathioprine before and after deprotonation.                 KEY WORDS: Azathioprine, Spectral study, Thermal study, Decomposition products, DFT Bull. Chem. Soc. Ethiop. 2022, 36(1), 73-84.                                                                   DOI: https://dx.doi.org/10.4314/bcse.v36i1.

A new simple route for synthesis of cadmium(II), zinc(II), cobalt(II), and manganese(II) carbonates using urea as a cheap precursor and theoretical investigation

ABSTRACT. The MnCO3.H2O, CoCO3.4H2O, ZnCO3, and CdCO3, respectively, were synthesized through a new precise, easy pathway for the reaction of MnI2, CoI2, ZnI2, or CdI2 aqueous solutions with a cheap precursor-urea for 10 h at ~ 70 oC. The IR spectra of reaction products designate the presence of characteristic bands of ionic carbonate, CO32– and absence of the individual bands of urea. The (CO3)2- ion is planar and therefore, it belongs to the D3h symmetry. It is expected to display four modes of vibrations. The stretching vibrations of the type; n(C-O) is observed in the range of (1376-1503) cm-1 while another stretching vibration n(C-O) is observed in the region 1060-1079 cm-1. The out of plane of vibration d(OCO) is observed in the range of (833-866) cm-1 while, the angle deformation bending vibration d(OCO) appear in the range of (708-732) cm-1. The infrared spectra of metal carbonate, show that, this product clearly has an uncoordinated water. The band related to the stretching vibration n(O-H) of uncoordinated H2O is observed as expected in the range of ~ 3000 cm-1. A general mechanism explaining the synthesis of carbonate compounds of cadmium(II), zinc(II), cobalt(II), and manganese(II), are described. Moreover, the DFT outcomes using B3LYP/LanL2DZ (basis set) agree with the experimental results.                 KEY WORDS: Carbonate, CoI2, Infrared spectra, Urea, DFT   Bull. Chem. Soc. Ethiop. 2022, 36(2), 363-372.                                                                DOI: https://dx.doi.org/10.4314/bcse.v36i2.10                                                     &nbsp

Potential inhibitory activity of phytoconstituents against black fungus: in silico admet, molecular docking and MD simulation studies

Mucormycosis or “black fungus” has been currently observed in India, as a secondary infection in COVID-19 infected patients in the post-COVID-stage. Fungus is an uncommon opportunistic infection that affects people who have a weak immune system. In this study, 158 antifungal phytochemicals were screened using molecular docking against glucoamylase enzyme of Rhizopus oryzae to identify potential inhibitors. The docking scores of the selected phytochemicals were compared with Isomaltotriose as a positive control. Most of the compounds showed lower binding energy values than Isomaltotriose (-6.4 kcal/mol). Computational studies also revealed the strongest binding affinity of the screened phytochemicals was Dioscin (-9.4 kcal/mol). Furthermore, the binding interactions of the top ten potential phytochemicals were elucidated and further analyzed. In-silico ADME and toxicity prediction were also evaluated using SwissADME and admetSAR online servers. Compounds Piscisoflavone C, 8-O-methylaverufin and Punicalagin exhibited positive results with the Lipinski filter and drug-likeness and showed mild to moderate of toxicity. Molecular dynamics (MD) simulation (at 300 K for 100 ns) was also employed to the docked ligand-target complex to explore the stability of ligand-target complex, improve docking results, and analyze the molecular mechanisms of protein-target interactions

Novel thiophene Chalcones-Coumarin as acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, molecular docking, ADMET prediction and molecular dynamics simulation

A series of around eight novel chalcone based coumarin derivatives (23a-h) was designed, subjected to in-silico ADMET prediction, synthesized, characterized by IR, NMR, Mass analytical techniques and evaluated as acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease (AD). The results of predicted ADMET study demonstrated the drug-likeness properties of the titled compounds with developmental challenges in lipophilicity and solubility parameters. The in vitro assessment of the synthesized compounds revealed that all of them showed significant activity (IC50 ranging from 0.42 to 1.296 µM) towards AChE compared to the standard drug, galantamine (IC50 = 1.142 ± 0.027 µM). Among these, compound 23e displayed the most potent inhibitory activity with IC50 value of 0.42 ± 0.019 µM. Cytotoxicity of all compounds was tested on normal human hepatic (THLE-2) cell lines at three different concentrations using the MTT assay, in which none of the compound showed significant toxicity at the highest concentration of 1000 µg/ml compared to the control group. Based on the docking study against AChE, the most active derivative 23e was orientated towards the active site and occupied both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the target enzyme. In-silico studies revealed tested showed better inhibition activity of AChE compared to Butyrylcholinesterase (BuChE). Molecular dynamics simulation explored the stability and dynamic behavior of 23e- AChE complex

Crystal Structure, Topology, DFT and Hirshfeld Surface Analysis of a Novel Charge Transfer Complex (L3) of Anthraquinone and 4-{[(anthracen-9-yl)meth-yl] amino}-benzoic Acid (L2) Exhibiting Photocatalytic Properties: An Experimental and Theoretical Approach

Here, we report a facile route to the synthesizing of a new donor–acceptor complex, L3, using 4-{[(anthracen-9-yl)meth-yl] amino}-benzoic acid, L2, as donor moiety with anthraquinone as an acceptor moiety. The formation of donor–acceptor complex L3 was facilitated via H-bonding and characterized by single-crystal X-ray diffraction. The X-ray diffraction results confirmed the synthesized donor–acceptor complex L3 crystal belongs to the triclinic system possessing the P-1 space group. The complex L3 was also characterized by other spectral techniques, viz., FTIR and UV absorption spectroscopy, which confirmed the formation of new bonds between donor L2 moiety and acceptor anthraquinone molecule. The crystallinity and thermal stability of the newly synthesized complex L3 was confirmed by powdered XRD and TGA analysis and theoretical studies; Hirshfeld surface analysis was performed to define the type of interactions occurring in the complex L3. Interestingly, theoretical results were successfully corroborated with experimental results of FTIR and UV absorption. The density functional theory (DFT) calculations were employed for HOMO to LUMO; the energy gap (∆E) was calculated to be 3.6463 eV. The complex L3 was employed as a photocatalyst for the degradation of MB dye and was found to be quite efficient. The results showed MB dye degraded about 90% in 200 min and followed the pseudo-first-order kinetic with rate constant k = 0.0111 min−1 and R2 = 0.9596. Additionally, molecular docking reveals that the lowest binding energy was −10.8 Kcal/mol which indicates that the L3 complex may be further studied for its biological applications

Design and characterization of a binary CT complex of imidazole-oxyresveratrol: exploring its pharmacological and computational aspects

A new binary charge transfer (CT) complex between imidazole (IMZ) and oxyresveratrol (OXA) was synthesized and characterized experimentally and theoretically. The experimental work was carried out in solution and solid state in selected solvents such as chloroform (CHL), methanol (Me-OH), ethanol (Et-OH), and acetonitrile (AN). The newly synthesized CT complex (D1) has been characterized by various techniques such as UV-visible spectroscopy, FTIR, 1H-NMR, and powder-XRD. The 1:1 composition of D1 is confirmed by Jobs’ method of continuous variation and spectrophotometric (at λmax 554 nm) methods at 298 K. The infrared spectra of D1 confirmed the existence of proton transfer hydrogen bond beside charge transfer interaction. These findings indicate that the cation and anion are joined together by the weak hydrogen bonding as N+–H–O–. Reactivity parameters strongly recommended that IMZ behaves as a good electron donor and OXA an efficient electron acceptor. Density functional theory (DFT) computations with basis set B3LYP/6-31G (d,p) was applied to support the experimental results. TD-DFT calculations gives HOMO (−5.12 eV) → LUMO (−1.14 eV) electronic energy gap (ΔE) to be 3.80 eV. The bioorganic chemistry of D1 was well established after antioxidant, antimicrobial, and toxicity screening in Wistar rat. The type of interactions between HSA and D1 at the molecular level was studied through fluorescence spectroscopy. Binding constant along with the type of quenching mechanism, was investigated through the Stern-Volmer equation. Molecular docking demonstrated that D1 binds perfectly with human serum albumin and EGFR (1M17) and exposes free energy of binding (FEB) values of −295.2 and −283.3 kcal/mol, respectively. The D1 fits successfully into the minor groove of HAS and 1M17, the results of molecular docking show that the D1 binds perfectly with the HAS and 1M17, the higher value of binding energy shows stronger interaction between HAS and 1M17 with D1. Our synthesized complex shows good binding results with HAS compared to 1M17. Communicated by Ramaswamy H. Sarma</p

DFT Analysis and Synthesis of Medicinally Important Pyrrolo[2,3-d]Pyrimidines by Using Thiamine Hydrochloride as a Recyclable Organocatalyst in Aqueous Media

A facile, environmentally benign and proficient route has been developed for the diverse synthesis of pyrrolo[2,3-d]pyrimidine derivatives followed by heterocyclization starting from Amino uracil, arylgyoxal and malononitrile/thiols. Readily available thiamin hydrochloride organocatalyst was used as a green promoting medium. As well as the reaction progress was taken place under aqueous media. This procedure also offers a base and metal free approach which endowed high yields with better functional group tolerating ability and mild reaction conditions. Further, methodology had a widescope with recyclability and reuse of thiamin hydrochloride. DFT/TD-DFT calculations with B3LYP/6-311G++ level of theory were used to study the optimized geometry and HOMO-LUMO energy of the synthesized compounds (4b and 6i).</p

Enhancing the Antipsychotic Effect of Risperidone by Increasing Its Binding Affinity to Serotonin Receptor via Picric Acid: A Molecular Dynamics Simulation

The aim of this study was to assess the utility of inexpensive techniques in evaluating the interactions of risperidone (Ris) with different traditional &pi;-acceptors, with subsequent application of the findings into a Ris pharmaceutical formulation with improved therapeutic properties. Molecular docking calculations were performed using Ris and its different charge-transfer complexes (CT) with picric acid (PA), 2,3-dichloro-5,6-dicyanop-benzoquinon (DDQ), tetracyanoquinodimethane (TCNQ), tetracyano ethylene (TCNE), tetrabromo-pquinon (BL), and tetrachloro-p-quinon (CL), as donors, and three receptors (serotonin, dopamine, and adrenergic) as acceptors to study the comparative interactions among them. To refine the docking results and further investigate the molecular processes of receptor&ndash;ligand interactions, a molecular dynamics simulation was run with output obtained from AutoDock Vina. Among all investigated complexes, the [(Ris) (PA)]-serotonin (CTcS) complex showed the highest binding energy. Molecular dynamics simulation of the 100 ns run revealed that both the Ris-serotonin (RisS) and CTcS complexes had a stable conformation; however, the CTcS complex was more stable

Spectroscopic and Molecular Docking Analysis of π-Acceptor Complexes with the Drug Barbital

The drug barbital (Bar) has a strong sedative–hypnotic effect. The intermolecular charge transfer compounds associated with the chemical reactions between Bar and some π acceptors, such as 2,6-dibromoquinone-4-chloroimide (DBQ), tetracyanoquinodimethane (TCNQ), chloranil (CHL), and chloranilic acid (CLA), have been synthesized and isolated in solid state. The synthesized products have the molecular formulas (Bar–DBQ), (Bar–TCNQ), (Bar–CHL), and (Bar–CLA) with 1:1 stoichiometry based on Raman, IR, TG, 1H NMR, XRD, SEM, and UV-visible analysis techniques. Additionally, the comparative analysis of molecular docking between the donor reactant moiety, Bar, and its four CT complexes was conducted using two neurotransmitter receptors (dopamine and serotonin). The docking results obtained from AutoDockVina software were investigated by a molecular dynamics simulation technique with 100ns run. The molecular mechanisms behind receptor–ligand interactions were also looked into. The DFT computations were conducted using theory at the B3LYP/6-311G++ level. In addition, the HOMO LUMO electronic energy gap and the CT complex’s optimal geometry and molecule electrostatic potential were examined

Multispectral and Molecular Docking Studies Reveal Potential Effectiveness of Antidepressant Fluoxetine by Forming π-Acceptor Complexes

Poor mood, lack of pleasure, reduced focus, remorse, unpleasant thoughts, and sleep difficulties are all symptoms of depression. The only approved treatment for children and adolescents with major depressive disorder (MDD) is fluoxetine hydrochloride (FXN), a serotonin selective reuptake inhibitor antidepressant. MDD is the most common cause of disability worldwide. In the present research, picric acid (PA); dinitrobenzene; p-nitro benzoic acid; 2,6-dichloroquinone-4-chloroimide; 2,6-dibromoquinone-4-chloroimide; and 7,7′,8,8′-tetracyanoquinodimethane were used to make 1:1 FXN charge-transfer compounds in solid and liquid forms. The isolated complexes were then characterized by elemental analysis, conductivity, infrared, Raman, and 1H-NMR spectra, thermogravimetric analysis, scanning electron microscopy, and X-ray powder diffraction. Additionally, a molecular docking investigation was conducted on the donor moiety using FXN alone and the resulting charge transfer complex [(FXN)(PA)] as an acceptor to examine the interactions against two protein receptors (serotonin or dopamine). Interestingly, the [(FXN)(PA)] complex binds to both serotonin and dopamine more effectively than the FXN drug alone. Furthermore, [(FXN)(PA)]–serotonin had a greater binding energy than [FXN]–serotonin. Theoretical data were also generated by density functional theory simulations, which aided the molecular geometry investigation and could be beneficial to researchers in the future