Spectroscopic study and molecular simulation: Bovine serum albumin binding with anticancer Pt complex of amyl dithiocarbamate ligand.

Until now, many methods have been proposed to treat cancer, such as radiation therapy and drug therapy, but none of them have caused a complete cure for cancer. Heavy metal complexes such as cisplatin are among the compounds used as drugs in chemotherapy against cancer cells. These compounds cause cell death and have anti-cancer properties, but they have side effects. The biochemical mechanism of cisplatin is related to its interaction with DNA through covalent binding. To reduce the toxicity of metallodrugs, new complexes can be designed containing S, S- bidentate ligands such as diethyldithiocarbamate. Moreover, anti-cancer compounds probably interact with proteins, such as HSA, before passing the cancerous cell membrane and DNA as a target. So, the function of proteins and their stabilities are expected to change. In this research, the mode of binding of [Pt (bpy) (amyl.dtc)]NO3 complex with BSA was evaluated by various thermodynamic methods. Negative binding enthalpy and entropy changes amounts show that the connection between the Platinum compound and BSA occurs via the van Der Waals type of hydrogen bond. The negative Gibbs free energy change was obtained through isothermal titration, which showed interaction proceeds spontaneously. Moreover, the emission titration data showed that protein fluorescence quenching by platinum agent titration is static. Binding, quenching constants, and binding site number were obtained by the Stern-Volmer equation, and only one binding site was determined for this interaction. A Scatchard plot with a positive slope shows the Pt agent-BSA formation is proceeding positively cooperative. The kinetic study displayed that the absorption monitoring followed the second-order model. Finally, molecular docking simulation showed that the position of the Pt agent on protein is placed I under region II.

Platinum (II) complex of isopentyl glycine ligand: DNA binding, molecular dynamic, and anticancer activity against breast cancer.

In this paper, we performed thorough experimental and theoretical calculations to examine the interaction between Pt derivative, as an anticancer, and ct-DNA. The mode of DNA binding with [Pt(NH3)2(Isopentylgly)]NO3, where Isopentylgly is Isopentyl glycine, was evaluated by various spectroscopic methods, docking, and molecular dynamics simulation studies. UV-Vis and fluorescence spectroscopic titration results and CD spectra of DNA-drug showed this interaction is via groove binding. Also, thermal stability studies or DNA melting temperature changes (ΔTm), as well as the quenching emissions monitoring proved it. Also, the thermodynamic parameter and binding constant displayed that complex-DNA formation is a spontaneous process, and H-binding and also groove binding were found to be the main forces. Theoretical studies stated [Pt(NH3)2(Isopentylgly)]NO3-DNA formation occurs on C-G center on DNA, along with rising DNA-compound stability. IC50 value against the human breast cell line probably is due to the Isopentyl glycine ligand in the structure of the Pt compound, and it was obtained more than cisplatin and less than carboplatin against the MCF7 cell.Communicated by Ramaswamy H. Sarma.

Adsorption of folic acid molecule on diphenylalanine peptide nanohole as a drug delivery in cancer treatment: a molecular dynamics simulation study.

CONTEXT: Using the molecular dynamics simulation method, the adsorption of folic acid as a drug with diphenylalanine peptide nanohole as an efficient nanodrug delivery system was investigated computationally. It focuses on the structural properties, drug loading capacity in the carrier, intermolecular interactions, and drug encapsulation behaviors. The results show that the average number of hydrogen bonds between diphenylalanine and folic acid will increase when the system reaches equilibrium. In addition, by increasing the weight concentration of folic acid from 0.3 to 0.9%, the number of hydrogen bond between them increases about 18%. In other words, hydrogen bonding can play an effective role in the binding of folic acid to the drug carrier. The results of the radial distribution function of water molecules around the carrier mass center show that its effective radius is around 1.2 nm (or 12 Å), which is in a good agreement with the results obtained from the hydrodynamic radius. METHOD: The initial structures were optimized in Amber molecular mechanics using Gaussian 09 software in aqueous medium in DFT/B3LYP/6-31 g(d). The molecular structure of folic acid was obtained from the PubChem database. The initial parameters are embedded in AmberTools. To calculate partial charges, restrained electrostatic potential (RESP) method was used. Gromacs 2021 software, modified water model (SPC/E), and Amber 03 force field have been used in all simulations. VMD software was used to view simulation photos.

Spectroscopy and molecular dynamic study of the interaction of calf thymus DNA by anticancer Pt complex with butyl glycine ligand.

Despite the past few decades since the discovery of anticancer drugs, there is still no definitive treatment for its treatment. Cisplatin is a chemotherapy medication used to treat some cancers. In this research, the DNA binding affinity of Pt complex with butyl glycine ligand was studied by various spectroscopy methods and simulation studies. Fluorescence and UV-Vis spectroscopic data showed groove binding in ct-DNA-[Pt(NH3)2(butylgly)]NO3 complex formation by the spontaneous process. The results were also confirmed by small changes in CD spectra and thermal study (Tm), as well as the quenching emission of [Pt(NH3)2(butylgly)]NO3 complex on DNA. Finally, thermodynamic and binding parameters displayed that hydrophobic forces are the main forces. Based on docking simulation, [Pt(NH3)2(butylgly)]NO3 could bind to DNA and via minor groove binding on C-G center on DNA, formed a stable DNA complex.

Luminescent excited-state intramolecular proton-transfer dyes based on 4-functionalized 6,6'-dimethyl-3,3'-dihydroxy-2,2'-bipyridine (BP(OH)2-Rs); DFT simulation study.

The 4-functionalized 6,6'-dimethyl-3,3'-dihydroxy-2,2'-bipyridine dyes (BP(OH)2-Rs) have exhibited dienol and diketo emissions. The optimum geometrical structures for ground, singlet and triplet excited states are computed by DFT/B3LYP/6-31++G that showed the planarity of BP(OH)2-Rs structure. The emission spectra of the molecules are determined in the gas-phase at singlet and triplet excited states using CIS/6-31++G. The theoretical calculations are carried out for BP(OH)2-Rs to understand the impact of different substituents (R = -H (I), -Br (II), -TMS (III), -C2H (IV), -terpyridine (V) and -bodipy (diazaboraindacene) (VI)) on excited-state intramolecular proton transfer (ESIPT) in singlet and triplet excited states. Based on the calculations, the concerted diproton transfer proceeds in the triplet excited state, in which nπ* state has a significant participation in ESIPT. The spectral variation at ESIPT emission of BP(OH)2-Rs is influenced by the electron-acceptor ability of the substituents. The compound V revealed a higher spectral intensity compared to the others. From the comparison with the experimental data, the molecule V is almost planar agreed with the X-ray structure and trend variation of wavelengths. The molecule VI contains bodipy chromophore that excitation energy transfers completely from BP(OH)2 core to a bodipy substituent, leading to emission from the lowest-lying bodipy substituent, and consequently, ESIPT does not occur for this dye.

Spectroscopic and docking molecular study of new anticancer Pt complex binding with human serum albumin.

After synthesizing and identifying the nature of the new complex based on platinum metal, [Pt(NH3)2(butylgly)]NO3, the interaction of this complex with human serum albumin (HSA) was performed by spectroscopy and molecular docking methods at two temperatures of 27 and 37 °C and under physiological conditions of the body. The toxicity test of this complex was performed on the MCF-7 cell line (IC50 = 300 µM). Enthalpy, entropy, Gibbs free energy, binding constant, number of complex binding sites on the HSA, Scatchard diagrams, Hill coefficient, and Hill constant were calculated and then plotted via UV/Vis. According to the Gibbs free energy obtained at two temperatures of 27 and 37 °C (-20.6, -21.2 kJ mol-1), the interaction was done spontaneously. Moreover, the melting temperature of human serum albumin with this complex; and the kinetics of this interaction (the second-order) were calculated. Using fluorescence at three temperatures of 25, 27, and 37 °C, the binding constant (2.9 × 104, 1.0 × 104, and 5.7 × 103 M-1), the quenching constant, average aggregation number of HSA, and the number of binding sites of the complex on the protein were obtained. As well, the static quenching mechanism was also observed. Molecular docking results showed that the site of binding of this complex to the HSA, is the site II subdomain IIIA, and the hydrogen and hydrophobic bonds are superior.

Kinetic and Thermodynamic Investigation of Human Serum Albumin Interaction with Anticancer Glycine Derivative of Platinum Complex by Using Spectroscopic Methods and Molecular Docking.

In this paper, a new anticancer Pt (II) complex, cis-[Pt (NH3)2(tertpentylgly)]NO3, was synthesized with glycine-derivative ligand and characterized. Cytotoxicity of this water-soluble Pt complex was studied against human cancer breast cell line of MCF-7. The interaction of human serum albumin (HSA) with Pt complex was studied by using UV-Vis, fluorescence spectroscopy methods, and molecular docking at 27 and 37 °C in the physiological situation (I = 10 mM, pH = 7.4). The negative [Formula: see text] and positive [Formula: see text] indicated that electrostatic force may be a major mode in the binding between Pt complex and HSA. Binding constant values were obtained through UV-Vis and fluorescence spectroscopy that reveal strong interaction. The negative Gibbs free energy that was obtained by using the UV-Vis method offers spontaneous interaction. Fluorescence quenching the intensity of HSA by adding Pt complex confirms the static mode of interaction is effective for this binding process. Hill coefficients, nH, Hill constant, kH, complex aggregation number around HSA, , number of binding sites, g, HSA melting temperature, Tm, and Stern-Volmer constant, kSV, were also obtained. The kinetics of the interaction was studied, which showed a second-order kinetic. The results of molecular docking demonstrate the position of binding of Pt complex on HSA is the site I in the subdomain IIA.

A combined computational and experimental study of the [Co(bpy)3](2+/3+) complexes as one-electron outer-sphere redox couples in dye-sensitized solar cell electrolyte media.

A combined experimental and computational investigation conducted to understand the nature of the interactions between cobalt II/III redox mediators ([Co(bpy)3](2+/3+)) and their impact on the performance of the corresponding dye-sensitized solar cells (DSCs) is reported. The fully optimized equilibrium structures of cobalt(II/III)-tris-bipyridine complexes in the gas phase and acetonitrile solvent are obtained by the density functional B3LYP method using LanL2DZ and 6-31G(d,p) basis sets. The harmonic vibrational frequencies, infrared intensities and Raman scattering activities of the complexes are also calculated. The scaled computational vibrational wavenumbers show very good agreement with the experimental values. Calculations of the electronic properties of the complexes are also performed at the TD-B3LYP/6-31G(p,d)[LanL2DZ] level of theory. Detailed interpretations of the infrared and Raman spectra of the complexes in different phases are reported. Detailed atomic orbital coefficients of the frontier molecular orbitals and their major contributions to electronic excitations of the complexes are also reported. These results are in good agreement with the experimental electrochemical values. Marcus diagram is derived for the electron transfer reaction Co(II) + D35(+)→ Co(III) + D35 using the Co-N bond length as a reaction coordinate.

Charge transfer in some complexes of crown ether and of thiacrown ether with dihalogens: DFT study.

The present study was carried out by focusing on the interaction between molecular complexes crown and thiacrown ethers such as 15-crown-5 (15C5), thia-15-crown-5 (T15C5), dithia-15-crown-5 (DT15C5) with homogeneous and heterogeneous dihalogens (XY) such as I2, IBr, ICl, Br2, Cl2 in the gas phase and in dichloromethane solvent through applying density function theory (DFT) as well as Gaussian 98 programs series. Characteristics such as frequency, enthalpy of reaction and energy have been totally specified. Special attention was placed on the study of electronegativity of outer halogen atom and polarization of bond between two halogens on the interaction. Results indicate that electronegativity of the external halogen atom and the polarization of dihalogen bond have remarkable effects on structure parameters, donor-acceptor effect, structural stabilization, and the enthalpy of the complex product. It is concluded that the charge transfer takes place in three complexes: 15C5, T15C5, and DT15C5; and the direction of charge transfer is from crown and thiacrown molecule to dihalogen. Stability of 15C5, T15C5 and DT15C5 complexes according to the energy is ICl > IBr > I2. The optimum condition for maximum stability of the molecular complex M…IY is optimized plane structure and the optimum level of polarization of dihalogen during complexation of 15C5, T15C5, and DT15C5 is ICl molecule. The study of the interaction in dichloromethane solvent has similar results to the gas phase. An analysis of the NBO confirms the obtained results.

A study of donor-acceptor in the charge transfer molecular complexes of some thiacrown ethers with dihalogen molecules by DFT method.

The molecular complexes of 1,3,5-trithiane, (TT), tetrathia-8-crown-4, (TT8C4), and trithia-9-crown-3 , (TT9C3) with dihalogens in the ground state were investigated in the gas and dicholoromethane phases using B3LYP method and 6-31G** and 6-31+G** bases sets. In both TT and TT8C4 complexes, it is predicted that charge transfer takes place from the dihalogen to the thiacrown ether molecule; the magnitude trend of the total CT was ICl > IBr > I2, and Cl2 > Br2 > I2, respectively. There was not such a trend with TT9C3. The frequency analysis showed that all complexes in the excited state were unstable. The analysis of natural bond orbitals and comparison of the calculated thermodynamic quantities of the complexes between the gas phase and tetrachloromethane solution confirmed the results.