Comparative Linkage of Novel Anti-Tumor Pd(II) Complex with Bio-Macromulecules: Fluorescence, UV-Vis, DFT, Molecular Docking and Molecular Dynamics Simulation Studies.

A novel mononuclear palladium complex, [Pd(dach)(SSA)], where dach and SSA are diaminocyclohexane and sulfosalicylic acid ligands, respectively, has been synthesized and identified utilizing analytical and spectral methods. DFT calculations, namely geometry optimization, MEP, HOMO-LUMO and NBO analysis, have been conducted at B3LYP level by aug-ccpVTZ-PP and 6-311G(d, p) basis sets. NBO and HOMO-LUMO analysis exhibited that the palladium compound is stable. MEP showed the potential sites of molecule for the interaction. By employing MTT assay, the cytotoxicity activity of the aforesaid compound was examined on K562 cell line, which revealed a proper activity compared to cisplatin. To ascertain the lipophilicity of the newly made compound, the partition coefficient measurement was accomplished, which follows the order of cisplatin < Pd(II) complex. Next, investigation of binding properties of the studied compound with DNA of calf thymus and BSA were done by spectroscopic (CD, fluorescence emission and electronic adsorption) and non-spectroscopic (viscosity measurements, DNA gel electrophoresis, molecular docking and molecular dynamics simulation) methods. The outcomes of CD and UV-Vis spectroscopy demonstrated that the title compound refolded the protein via increasing the alpha helix percentage. The data obtained from UV-Vis studies indicated the non-intercalative mutual action between Pd(II) complex with DNA. It also revealed that the Kapp magnitude of CT-DNA (7.43 × 104 M- 1) is higher than the BSA (5.17 × 103 M- 1), and L1/2 (midpoint of transition) of CT-DNA (5 µM) is lower than the BSA (5.7 µM), indicating that the complex has a greater binding affinity to CT-DNA than BSA. Fluorescence quenching mechanism of the two biomolecules by the metal complex is static and the calculated thermodynamic parameters (ΔS° < 0 and ΔH° < 0) suggested the hydrogen bonding and/ or van der Waals forces with DNA and BSA. Further, molecular docking indicated that the studied compound fits into the groove of DNA and the site I of BSA. The stability of metal compound-DNA/-BSA in the presence of H2O solvent and over the time were validated via molecular dynamics simulation.

Effect of Cu(II) compound containing dipicolinic acid on DNA damage: a study of antiproliferative activity and DNA interaction properties by spectroscopic, molecular docking and molecular dynamics approaches.

A polymeric compound formulized as [Cu(µ-dipic)2{Na2(µ-H2O)4]n.2nH2O (I), where dipic is 2,6-pyridine dicarboxylic acid (dipicolinic acid, H2dipic), was synthesized by sonochemical irradiation. The initial in-vitro cytotoxic activity of this complex compared with renowned anticancer drugs like cisplatin, versus HCT116 colon cell lines, shows promising results. This study investigated the interaction mode between compound (I) and calf-thymus DNA utilizing a range of analytical techniques including spectrophotometry, fluorimetry, partition coefficient analysis, viscometry, gel electrophoresis and molecular docking technique. The results obtained from experimental methods reveal complex (I) could bind to CT-DNA via hydrogen bonding and van der Waals forces and the theoretical methods support it. Also, complex (I) indicates nuclease activity in the attendance of H2O2 and can act as an artificial nuclease to cleave DNA with high efficiency.Communicated by Ramaswamy H. Sarma.

Synthesis, crystal structure, cytotoxicity, in-detail experimental and computational CT-DNA interaction studies of 2-picolinate Pd(II) and Pt(II) complexes.

A new Pd(II) complex of formula [Pd(en)(2-pyc)]+ (where, en is ethylenediamine and 2-pyc is 2-pyridinecarboxylate anion) and its reported Pt(II) analogue, i.e. [Pt(en)(2-pyc)]+ have been made by an improved synthetic procedure, yielding above 80%. They have been characterized by FT-IR, UV-Vis, 1H NMR, 13C NMR, conductivity and elemental analysis. Single crystal structural determination of [Pt(en)(2-pyc)]+ displayed that the Pt(II) cation in this complex coordinated by 2-pyc and en each as five member chelate resulting in slightly distorted square-planar array. The time-dependent spectroscopic analysis of these compounds in aqueous medium demonstrated their structural stabilities. The cytotoxic activities of Pd(II) and Pt(II) complexes, free 2-pyc and carboplatin (as standard drug) were assayed in-vitro against the HCT-116 and MCF-7 as cancerous and MCF 10 A and CCD-841 as normal cell lines. They showed the IC50 order of: carboplatin > 2-pyc > Pt(II) > Pd(II) and lower activities against non-cancerous cells. CT-DNA binding of the Pd(II), Pt(II) and 2-pyc free ligand were explored individually. In this relation, UV-Vis and fluorescence titrations disclosed quenching of CT-DNA absorption and emissions by the compounds via dynamic mechanism and formation of H-bonds and van der Waals forces between them. The interaction was further validated and verified by viscosity measurements and gel electrophoresis. Partition coefficient determination showed that all three compounds have more lipophilicity than cisplatin. Furthermore, docking analysis and molecular dynamics simulation were done to evaluate the nature of interaction between aforementioned compounds and CT-DNA. The finding results demonstrated that these agents interact with CT-DNA via groove binding and were in agreement with experimental results.Communicated by Ramaswamy H. Sarma.

Computational and experimental examinations of new antitumor palladium(II) complex: CT-DNA-/BSA-binding, in-silico prediction, DFT perspective, docking, molecular dynamics simulation and ONIOM.

Since the design of metal complexes with better biological activities is important, herein a new palladium(II) complex bearing en and acac (en and acac stand for ethylenediamine and acetylacetonato, respectively) as its ligands, [Pd(en)(acac)]NO3 complex, was synthesized and fully characterized. Quantum chemical computations of the palladium(II) complex were done via DFT/B3LYP method. Cytotoxicity activity of the new compound on leukemia cell line (K562) was assessed via MTT method. The findings indicated that the metal complex has remarkable cytotoxic effect than cisplatin. OSIRIS DataWarrior software was employed to calculate in-silico physicochemical and toxicity parameters of the synthesized complex which rendered significant results. To comprehend the interaction type of new metal compound with macromolecules, the in depth investigation of interaction of mentioned complex with CT-DNA and BSA was accomplished by fluorescence, UV-Visible absorption spectroscopy, viscosity measurement, gel electrophoresis, FRET analysis and circular dichroism (CD) spectroscopy. On the other hand, computational molecular docking was carried out and the obtained data demonstrated that H-bond and van der Waals forces are the dominant forces for the binding of the compound to the mentioned biomolecules. Molecular dynamics simulation was also done and confirmed the stability of best docked pose of palladium(II) complex inside DNA or BSA over the time and in presence of water solvent. Also, Our own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) methodology based on the hybridization of quantum mechanics and molecular mechanics (QM/MM) methodology was accomplished to inquire about binding of Pd(II) complex with DNA or BSA.Communicated by Ramaswamy H. Sarma.

New biologically active Pd(II) complex was synthesized and characterized.The in silico studies of the designed complex and its ligands were accomplished by OSIRIS DataWarrior softwareInteraction with CT-DNA and BSA was assessed by various spectroscopic methods.Molecular docking simulation supported the interaction with both macromolecules.Based on ONIOM analysis, the structures of the complex and biomolecules are altered after binding.

Exploring the Interaction Between the Newly Designed Antitumor Zn(II) Complex and CT-DNA/BSA: Spectroscopic Methods, DFT Computational Analysis, and Docking Simulation.

A new zinc(II) complex formulated as [Zn(pipr-ac)2], where pipr-ac stands for piperidineacetate, was synthesized and structurally identified with the help of experimental and DFT methods. Frontier molecular orbital (FMO) analysis demonstrated that the new complex has higher biological activity compared to the free ligand. Molecular electrostatic potential (MEP) showed the nitrogen atoms and oxygen of carbonyl groups are the active sites of Zn(II) compound. Also, natural bond orbital (NBO) analysis confirmed the charge transfer from the ligating atoms to the metal ion and formation of four coordinated Zn(II) complex. MTT assay illustrated a noticeable cytotoxic activity of the new zinc(II) complex compared to cisplatin on K562 cell line. The CT-DNA and serum albumin (SA) binding of the Zn(II) complex were explored individually. In this regard, UV-Vis spectroscopy and florescence titration revealed the occurrences of fluorescence quenching of CT-DNA/SA by metal compound via static mechanism and creation of hydrogen bonds and van der Waals interactions between them. The binding was further confirmed by viscosity measurement and gel electrophoresis assay for CT-DNA and circular dichroism spectroscopy for SA. Moreover, molecular docking simulation demonstrated that the new compound binds mainly through hydrogen bonds to the groove of DNA and hydrogen bonds and van der Waals interactions to site I of SA.

In-silico and in-detail experimental interaction studies of new antitumor Zn(II) complex with CT-DNA and serum albumin.

In this study, a novel Zn(II) complex with the formula [Zn(pyrr-ac)2] (pyrr-ac: pyrrolidineacetate) was synthesized and characterized through molar conductivity, elemental analysis, 1H Nuclear Magnetic Resonance (1H NMR), UV-Visible spectroscopy, and Fourier transform infrared (FT-IR) methods. B3LYP level of DFT method along with aug-cc-pVTZ-PP/6-311G(d,p) basis set was utilized to perform the geometry optimization and HOMO-LUMO analysis. In addition, MEP, NLO and NBO computations were also performed at the same level of theory. In vitro antitumor activity of the mentioned complex on leukemia cell line, K562, was investigated using the MTT assay which surprisingly revealed the effective antitumor activity of the studied zinc complex. Interaction of this compound with biological macromolecules viz., CT-DNA and BSA was studied via different spectroscopic methods. The results of fluorescence experiment displayed that the metal complex binds to both macromolecules through hydrogen bond (H-bond) and van der Waals (vdW) forces. UV-Vis tests indicated a decline in the absorption spectra of CT-DNA/BSA in the presence of the compound. The interaction was further corroborated for CT-DNA via gel electrophoresis, CD spectroscopy and viscosity experiments and for BSA using CD spectroscopy. Furthermore, molecular docking simulation was done to evaluate the nature of interaction between the aforementioned zinc complex and CT-DNA/BSA. These results were in agreement with experimental findings and demonstrated that the main interaction is hydrogen bonding. The above type of investigations may provide a pathway through which zinc complexes join the anticancer category.[Figure: see text]The in-silico and in-vitro results confirm that the newly made [Zn(pyrr-ac)2] complex interacts with CT-DNA than BSA.Communicated by Ramaswamy H. Sarma.

Biological activity of bis-(morpholineacetato)palladium(II) complex: Preparation, structural elucidation, cytotoxicity, DNA-/serum albumin-interaction, density functional theory, in-silico prediction and molecular modeling.

In an effort to discover a novel potential bioactive compound, a mono-nuclear Pd(II) complex with an amino acid derivative as ligand was synthesized and characterized through experimental and computational methodologies. A square-planar configuration was suggested for palladium(II) complex utilizing density functional theory. MEP map and Mulliken atomic charge were detected electrophilic and nucleophilic regions of the compound for reactions. The lipophilicity and cytotoxic activity of the complex was more effective than cisplatin. Also, OSIRIS DataWarrior revealed proper oral bioavailability and good drug-likeness for the compound. In-vitro binding behavior of the Pd(II) complex with DNA and serum albumin (BSA) were fully determined via variety of procedures including fluorescence, UV-Vis, CD, viscosity, gel electrophoresis experiments and molecular simulation. The negative signs of ΔH° and ΔS° for Pd(II) complex-CT-DNA/-BSA systems indicated the existence of hydrogen bonding/van der Waals interactions for both binding systems. Additionally, docking simulation illustrated the interaction of Pd(II) complex with the minor groove of DNA and the hydrophobic cavity of the BSA (drug binding site I).

Probing the interaction of new and biologically active Pd(II) complex with DNA/BSA via joint experimental and computational studies along with thermodynamic, NLO, FMO and NBO analysis.

Treatment with transition metal complexes is an efficient method to fight with cancer. Therefore, a new transition metal complex formulated as [Pd(1, 3-pn)(acac)]Cl (pn and acac stand for propylendiamine and acetylacetonate, respectively) was synthesized and analyzed using 1H NMR, Fourier transform infrared, electronic absorption spectroscopy techniques as well as elemental analysis and conductivity measurement. The geometry optimization, frontier molecular orbital (FMO) analysis, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis and nonlinear optical (NLO) property were accomplished by density functional theory (DFT) at B3LYP level with 6-311G(d,p)/aug-cc-pVTZ-PP basis set. Preliminary determination of antitumor activity and lipophilicity of this metal complex was performed experimentally and the promising results were obtained. This encouraged us to study the interaction and binding mode/modes of this complex with DNA as the primary receptor for the chemotropic drugs and BSA as the transporter protein in the circulatory system. For this reason, the binding of newly made complex was assessed in-vitro under physiological state using experimental and in-silico molecular modeling studies. So, the CT-DNA binding study of this complex was explored using spectrofluorometric as well as spectrophotometric techniques, viscosity and gel electrophoresis experiments. Furthermore, fluorescence, UV-Vis, F[Formula: see text]rster resonance energy transfer and circular dichroism studies were carried out for BSA binding. The experimental and computational interaction studies showed that [Pd(1, 3-pn)(acac)]Cl complex binds to the minor groove of CT-DNA and interacts with BSA by van der Waals forces and hydrogen bond.

Synthesis, characterization, cytotoxicity and DNA/BSA binding of two amino acid palladium(II) complexes derived from alanine and valine.

Two novel palladium(II)-amino acid complexes, [Pd(Ala)2]·H2O (PA) and [Pd(Val)2].H2O (PV) (Ala = alanine; Val = valine) were synthesized and characterized through FTIR, UV/Vis, 1H-NMR spectroscopies, CHN analysis, X-ray crystallography and molar conductivity measurement. Furthermore, cytotoxicity of Pd(II) complexes against human leukemia cancer cell line, MOLT4 showed promising cancer cell death (CC50 = 0.71 ± 0.046 µM for PA; CC50 = 0.85 ± 0.063 µM for PV) that were less than cisplatin (1.59 ± 0.25 µM). Moreover, the interaction of both the complexes with DNA and BSA was studied using UV-Vis absorption and emission spectroscopic techniques that demonstrated the bindings occurred via van der Waals forces and hydrogen bond. Furthermore, the fluorescence titration showed that static quenching mechanism plays predominate role in binding process. All results showed that both complexes have more binding tendency to DNA in compared to BSA that can be a significant achievement for further medical purposes as a potential antitumor candidate. Finally, molecular docking simulation was performed for PA and PV complexes with DNA and BSA and demonstrated both complexes bind to the groove of DNA mainly by hydrogen bond and interact with site I of BSA via hydrogen bond as well.

A novel palladium(II) antitumor agent: Synthesis, characterization, DFT perspective, CT-DNA and BSA interaction studies via in-vitro and in-silico approaches.

Since numerous people annually pass away due to cancer, research in this field is essential. Thus a newly made and water like palladium(II) complex of formula [Pd(phen)(acac)]NO3, where phen is 1,10-phenanthroline and acac is acetylacetonato ligand, has been synthesized by the reaction between [Pd(phen)(H2O)2](NO3)2 and sodium salt of acetylacetone in the molar ratio of 1:1. It has been structurally characterized via the methods such as conductivity measurement, elemental analysis and spectroscopic methods (FT-IR, UV-Vis and 1H NMR). The geometry optimization of this complex at the DFT level of theory reveals that Pd(II) atom is situated in a square-planar geometry. The complex has been screened for its antitumor activity against K562 cancer cells which demonstrated efficacious activity. The interaction of above palladium(II) complex with CT-DNA as a target molecule for antitumor agents and BSA as a transport protein was studies by a variety of techniques. The results of UV-Vis absorption and fluorescence emission indicated that the Pd(II) complex interacts with EB + CT-DNA through hydrophobic and with BSA by hydrogen bonding and van der Waals forces at very low concentrations. In these processes, the fluorescence quenching mechanism of both the macromolecules seems to be the combined dynamic and static. The interaction was further supported for CT-DNA by carrying out the gel electrophoresis and viscosity measurement and for BSA by the circular dichroism and Förster resonance energy transfer experiments. Furthermore, results of partition coefficient determination showed that the [Pd(phen)(acac)]NO3 complex is more lipophilic than that of cisplatin. Moreover, molecular docking simulation confirms the obtained results from experimental tests and reveals that the complex tends to be located at the intercalation site of DNA and Sudlow's site I of BSA.

Enhanced GROMACS: toward a better numerical simulation framework.

The GROMACS software package represented a promising direction toward the molecular dynamic simulation and there is ongoing interest to extend it. In this study, we introduce a new component into the conventional package with the goal being to facilitate the process of finding the native structure of proteins with minimal free-energy value. We achieved this through incorporating a wide range of metaheuristic optimization algorithms and force fields, leading up to the EGROMACS molecular simulation toolkit. Compared with other programs, the EGROMACS supports all standard force fields as well as new minimization algorithms and Hybrid MPI/OpenMP parallelization. We applied the proposed EGROMACS framework to minimize the structure of several target sequences. The obtained results showed comparative performance of the introduced framework to current well-known molecular simulation algorithms. This extension to the GROMACS, however, uses metaheuristic algorithms to address the problem.