Mansoureh Zahedi-Tabrizi

In this work, a metal–organic nickel framework (Ni-MOF) modified with a biological ligand (asparagine) (Ni-Bio-MOF) was synthesized by a hydrothermal method. Asparagine is believed to create defects on the surface of the MOF, thereby increasing its electrocatalytic activity. Then, a Diclofenac (DCF) polymer imprinted with L-methionine (PL-Met) was electrodeposited on a carbon paste electrode (CPE)/Ni-Bio-MOF and used as a new electrochemical sensor for highly selective and sensitive detection of DCF in biological and pharmaceutical samples. The Ni-Bio-MOF/MIP-PL-Met nanocomposite was characterized using the following techniques: FT-IR, FE-SEM, TEM, HR-TEM, XRD, XPS, and EDX. The electrochemical properties and performance of the sensor for the electrooxidation of DCF were assessed using CV, DPV, and EIS techniques. The electrochemical behavior of CPE/Ni-Bio-MOF/MIP-PL-Met and non-imprinted polymer (NIP) with an imprinting factor of 6.64 was investigated, and the influencing parameters in DCF measurement were optimized by cyclic voltammetry (CV). This modified sensor showed three dynamic ranges at 1.0–500.0 pM, 1.0–1000.0 nM, and 1.0–1000.0 μM of DCF with a limited detection (LOD) of 0.17 pM, sensitivity of 2015.5 μA μM⁻¹ cm⁻², relative standard deviation (RSD) of 3.3%, and reproducibility of 96.2%. Real samples of healthy human blood serum and DCF tablets were used to evaluate the practical application of the CPE/Ni-Bio-MOF/MIP-PL-Met electrochemical sensor. This method is simple, low-cost, with good limited detection, high sensitivity, and selectivity. The interactions of PL-Met with DCF were studied at the B3LYP/6-311++G(d,p) level of theory in both gaseous and aqueous phases. Additionally, the computational methodology investigated the thermodynamic stability of the proposed configurations and the role of hydrogen bonds in this system.

Schiff base complexes play a crucial role in bioinorganic chemistry. A novel curcumin/phenylalanine tridentate Schiff base ligand and its palladium (II) complex were synthesized so that they were stable in aqueous buffer. The structure of the complex was investigated using a variety of methods, including DFT, NBO analysis, FMOs, and MESP. The interaction of the complex with a plasmid (pUC19) and CT-DNA was studied. The anticancer, antibacterial, and antioxidant activities of the complex were examined. The statistical analysis of the MTT assay was compared using the 1-way ANOVA and Tukey test. Results showed that the complexes were stable in aqueous buffer, pH 8. The extrinsic fluorescence emission of the plasmid and CT-DNA was quenched while interacting with the complex. The complex had an IC₅₀ of 72.47 µM against MCF-7 cells. The ANOVA and Tukey analysis of MTT data demonstrated a statistically significant difference between groups (P < 0.0001). The minimum inhibitory concentrations (MIC) of the complex for E. coli and S. aureus were 300 and 200 µg/mL, with 96.3 and 95.2% biofilm growth inhibition at 250 µg/mL, respectively. The sample concentrations contributing to 50% radical inhibition in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test for curcumin, ligand, and palladium (II) complex were 33.62, 21.27, and 51.26 µM, respectively. The results suggest that the complex interaction with DNA is one of the potential mechanisms for eliminating cancer cells and bacteria in the planktonic and biofilm. On the other hand, while stability in an aqueous buffer at pH 8 increases, the modified curcumin antioxidant effect decreases.

Background: Leflunomide (LFM) and its active metabolite, teriflunomide (TFM), have drawn a lot of attention for their anticancer activities, treatment of rheumatoid arthritis and malaria due to their capability to inhibit dihydroorotate dehydrogenase (DHODH) and Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. In this investigation, the strength of intramolecular hydrogen bond (IHB) in five analogs of TFM (ATFM) was analyzed employing density functional theory (DFT) using B3LYP/6-311++G (d, p) level and molecular orbital analysis in the gas phase and water solution. A detailed electronic structure study was performed using the quantum theory of atoms in molecules (QTAIM) and the hydrogen bond energies (EHB) of stable conformer obtained in the range of 76-97 kJ/mol, as a medium hydrogen bond. The effect of substitution on the IHB nature was studied by natural bond orbital analysis (NBO). H-1 NMR calculations showed an upward trend in the proton chemical shift of the enolic proton in the chelated ring (14.5 to 15.7ppm) by increasing the IHB strength. All the calculations confirmed the strongest IHB in 5-F-ATFM and the weakest IHB in 2-F-ATFM. Molecular orbital analysis, including the HOMO-LUMO gap and chemical hardness, was performed to compare the reactivity of inhibitors. Finally, molecular docking analysis was carried out to identify the potency of inhibition of these compounds against PfDHODH enzyme. TFM acts as an inhibitor of dihydroorotate dehydrogenase (DHODH) and Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. Leflunomide and its active metabolite teriflunomide have been identified as drugs for treatment of some diseases, such as multiple sclerosis (MS), rheumatoid arthritis (RA), malaria, and cancer. Hydrogen bonds play a key role in the interaction between drugs and enzymes. Objectives: The aim of the present work is to investigate the effect of the strength of intramolecular hydrogen bonds (IHBs) in the active metabolite analogs of leflunomide or analogs of teriflunomide (ATFMs) and study the interaction of these inhibitors against the PfDHODH enzyme using quantum mechanical methods. Methods: At first, intramolecular hydrogen bonds in five ATFMs were evaluated by the DFT method, quantum theory of atoms in molecules (QTAIM), nuclear magnetic resonance (NMR), natural bond orbital (NBO), and molecular orbital (MO) analyses. Then, the interaction of these inhibitors against the PfDHODH enzyme were compared using molecular docking study. Results: All the computed results confirm the following trend in the intramolecular hydrogen bond strength in five mono-halo-substituted 2-cyano-3-hydroxy-N-phenylbut-2-enamide (ATFM): 5-F-ATFM> 4-Br-ATFM approximate to 3-Br-ATFM>3-Cl-ATFM>TFM-Z>2-F-ATFM which is in agreement with QTAIM, NMR, and NBO results. Docking results show that 5-F-ATFM (E-HB=97kJ/mol) has the minimum MolDock score due to its considerable IHB strength. Conclusion: For strong IHBs (E-HB>100kJ/mol), C=O and O-H group are involved in the intramolecular interactions and do not contribute to the external interactions. Also, the docking study revealed maximum binding energy between TFM-Z and PfDHODH enzyme.