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.

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.

A new palladium-based antiproliferative agent: synthesis, characterization, computational calculations, cytotoxicity, and DNA binding properties.

A new palladium(II) complex entitled [Pd(phendione)(8Q)]NO3, (PdPQ), where phendione is N,N-donor heterocyclic 1,10-phenanthroline-5,6-dion and 8Q is 8-hydroxyquinolinate, has been synthesized and then characterized by molar conductivity, CHN analysis and spectral data (UV-Vis, FT-IR, NMR). DFT/ TDDFT procedures were also performed to determine the electronic structure and the nature of the electronic transitions of PdPQ. Moreover, the affinity and binding properties of DNA to the desired complex have been studied in details using electronic absorption, fluorescence, circular dichroism spectroscopies, and viscosity measurement in combination with molecular docking technique. The obtained results exhibit relatively high DNA binding values with a static quenching mechanism, which suggest that an intercalative mode plays a peridominate role in interaction process concluded by experimental/theoretical measurements. As a result of drug exposure, in vitro cytotoxicity assay demonstrated the antiproliferative activity of the PdPQ against leukemia cancer cell line, K562.

Synthesis, characterization, cytotoxicity and DNA binding studies of a nNovel anionic organopalladium(II) complex.

A new anionic 8-hydroxyquinolinatopalladate(II) complex with malonate has been synthesized and characterized by elemental analysis, conductivity, FT-IR, UV-Vis and 1H NMR techniques to enhance the development of potential anticancer agents. Cytotoxicity was determined against the human leukemia cells, molt, by MTT assay. The novel antitumor Pd(II) complex was evaluated for its binding to calf thymus DNA (ctDNA) in physiological buffer (pH 7.0) by using absorption spectroscopy, fluorescence titration spectra, ethidium bromide displacement and gel chromatography studies. The results obtained from these analyses indicated that the water-soluble complex can bind to DNA cooperatively through a static quenching procedure at low concentrations. Thermodynamic parameters obtained from fluorescence experiments at different temperatures revealed the hydrogen binding and van der Waals force in the binding process which was supported by Scatchard's plots.

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.

Green Synthesis and Bioactivity of Aliphatic N-Substituted Glycine Derivatives.

Standard amino acids have an asymmetric α-carbon atom to which -COOH, -NH2, -H, and -R groups are bonded. Among them, glycine is the simplest (R = -H) with no asymmetric carbon, and other natural amino acids are C-substituted of glycine. Here, we have designed and made a green synthesis of some new N-substituted glycine derivatives with R-(NH)CH2-COOH formula, where R is flexible and hydrophobic with different chain lengths and benches of the type propyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl, 2-aminoheptyl, and octyl. These glycine derivatives were characterized by recording their melting points and FT-IR, mass, 1H NMR, and 13C NMR spectra. DFT studies revealed that 2-aminoheptyl glycine had the highest electronegativity value and can thus act as a good bidentate ligand for the metal centers. ADME comparative results and bioavailability radars indicated that both octyl- and 2-aminoheptyl glycine had the most lipophilicity, making them good agents in cell passing. Furthermore, lipophilicity determination showed that octyl glycine was the best and propylgly was more soluble than others. Based on solubility, lipophilicity, and dipole moment values, propyl- and 2-aminoheptyl-glycine were considered for bio-macromolecular interaction studies. Thus, the interaction of these two agents with DNA and HSA was studied using absorption spectroscopy and circular dichroism techniques. Due to the presence of the R-amine group, they can interact with the DNA by H-binding and hydrophobicity, while electrostatic mode could not be ruled out. Meanwhile, molecular docking studies revealed that octyl- and 2-aminoheptyl glycine had the highest negative docking energy, which reflects their higher tendency to interact with DNA. The DNA binding affinity of two candidate AAs was determined by viscosity measurement and fluorescence emission recording, which confirms that groove binding occurs. Also, the toxicity of these synthesized amino acid derivates was tested against the human foreskin fibroblast (HFF) cell line. They showed IC50 values within the range of 127-344 µM after 48 h with the highest toxicity for 2-aminoheptyl glycine.

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 interaction of Pt complex with imidazole derivative as an anticancer compound with DNA: Experimental and theoretical studies.

This investigation is applied to find out interesting information on DNA binding mode with Pt(II) derivative of two N, N bidentate ligands in treating cancer. Thus, one new water-soluble platinum complex with FIP and phen with a new formula of [Pt(phen)(FIP)](NO3)2 was prepared and specified. DFT data can be used to evaluate geometry parameters. Based on the ADMET prediction, this complex can be considered a drug-like agent. Cytotoxicity property was evaluated against some human cancerous MCF7, A549, and HCT116 cell lines. Accumulation of Pt complex, cisplatin, and oxaliplatin in each cancerous cell was determined, which is probably related to their lipophilicity and solubility properties. The binding mode of the complex to ct-DNA was investigated by fluorescence spectroscopy, circular dichroism, and molecular docking simulation. The viscosity of DNA by different concentrations of EB and Pt complex titration shows Pt complex interacts with DNA via groove binding like the spectroscopic binding result. In the MD study, DNA helix, RMSD, and RMSF analysis showed that DNA stability decreased and that the majority of residues left the initial state. DNA increased residual deviations and flexibility are linked to an increase in its gyratory radius, which is consistent with the findings of the experiments.

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.

High cancer selectivity and improving drug release from mesoporous silica nanoparticles in the presence of human serum albumin in cisplatin, carboplatin, oxaliplatin, and oxalipalladium treatment.

In this project, drug release was examined based on the adsorption of cisplatin, carboplatin, oxaliplatin, and oxalipalladium on aminated mesoporous silica nanoparticles (N-HMSNs) and human serum albumin (HSA). These compounds were characterized by different techniques where three clinical Pt-drugs, cisplatin, carboplatin, oxaliplatin, plus oxalipalladium were loaded and investigated for release. Based on loading analysis, the loading ability of the mentioned metallodrug on N-HMSNs was dependent on the nature of the drug structure as well as hydrophobic or hydrophilic interactions. Different adsorption and release profiles were observed for all mentioned compounds via dialysis and ICP method analysis. Although the maximum to minimum loading occurred for oxalipalladium, cisplatin, and oxaliplatin to carboplatin, respectively, release from a surface with greater control belonged to carboplatin to cisplatin systems in the absence and presence of HSA to 48 h due to weak interaction for carboplatin drug. The quick release of all mentioned compounds from the protein level at high doses of the drug during chemotherapy occurred very fast within the first 6 h. In addition, the cytotoxic activity of both free drugs and drug-loaded@N-HMSNs samples on cancerous MCF-7, HCT116, A549, and normal HFF cell lines was evaluated by MTT assay. It was found that free metallodrugs exhibited more active cytotoxic behavior on both cancerous and normal cell lines than drug-loaded@N-HMSNs. Data demonstrated that the Cisplatin@N-HMSNs with SI=6.0 and 6.6 for MCF7 and HCT116 cell lines, respectively, and Oxaliplatin@N-HMSNs with SI=7.4 for HCT116 cell line can be good candidates as an anticancer drug with minimal side effects by protecting cytotoxic drugs as well as controlled release and high selectivity.

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.

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).

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.

DNA-Binding Studies of Some Potential Antitumor 2,2'-bipyridine Pt(II)/Pd(II) Complexes of piperidinedithiocarbamate. Their Synthesis, Spectroscopy and Cytotoxicity.

In this study two platinum(II) and palladium(II) complexes of the type [M(bpy)(pip-dtc)]NO3 (where M=Pt(II) or Pd(II), bpy=2,2'-bipyridine, pip-dtc=piperidinedithiocarbamate) were synthesized by reaction between diaquo-2,2'-bipyridine Pt(II)/Pd(II) nitrate and sodium salt of dithiocarbamate. These cationic water soluble complexes were characterized by elemental analysis, molar conductance, IR, electronic and 1H NMR spectroscopic studies. The cyclic dithiocarbamate was found to coordinate as bidentate fasion with Pt(II) or Pd(II) center. Their biological activities were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The obtained cytotoxic concentration (IC50) values were much lower than cisplatin. The interaction of these complexes with highly polymerized calf thymus DNA (ct-DNA) was extensively studied by means of electronic absorption, fluorescence, circular dichroism and other measurements. The experimental results, thermodynamic and binding parameters, suggested that these complexes cooperatively bind to DNA presumably via intercalation. Moreover, the tendency of the Pt(II) complex to interact with DNA was more than that of Pd(II) complex.

DNA Binding and Antitumor Activity of α-Diimineplatinum(II) and Palladium(II) Dithiocarbamate Complexes.

The two water-soluble designed platinum(II) complex, [Pt(Oct-dtc)(bpy)]NO(3) (Oct-dtc = Octyldithiocarbamate and bpy = 2,2' -bipyridine) and palladium(II) complex, [Pd(Oct-dtc)(bpy)]NO(3), have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR, (1)H NMR, and electronic spectra studies. Studies of antitumor activity of these complexes against human cell tumor lines (K562) have been carried out. They show Ic(50) values lower than that of cisplatin. The complexes have been investigated for their interaction with calf thymus DNA (CT-DNA) by utilizing the electronic absorption spectroscopy, fluorescence spectra, and ethidium bromide displacement and gel filtration techniques. Both of these water-soluble complexes bound cooperatively and intercalatively to the CT-DNA at very low concentrations. Several binding and thermodynamic parameters are also described.

Interaction of bis(alkylamine)dichloropalladium(II) complexes with CT-DNA and BSA; their synthesis, characterization, antitumor, and antibacterial evaluations.

A series of five new and analogous palladium(II) alkylamine complexes of cisplatin derivatives such as cis-[Pd(alkyl-am)2Cl2], where alkyl-am is Ethyl-, Propyl-, Butyl-, Hexyl-, and Octyl-amine, have been prepared. They have been characterized by physicochemical methods such as FT-IR, 1H-NMR, UV-Vis, conductivity measurements and elemental analysis. These synthesized metal complexes were screened for their in-vitro antitumor activity against human MOLT-4 cells. Only [Pd(Octyl-am)2Cl2] showed moderate activity. They were also tested against some gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria by measuring the values of IZ, MIC and MBC. All Pd(II) complexes displayed comparable activity with that of cefazoline as standard antibiotics. To clarify the mode of interaction between these compounds and CT-DNA and (BSA), their interaction behavior was checked using electronic absorption spectroscopy. Results indicated that all of the above mentioned Pd(II) complexes effectively interacted with CT-DNA and BSA at low concentration and the distance between the interacted Pd(II) complexes and BSA were in the range of 3.00-3.30 nm. Fluorescence emission studies revealed that the complexes quenched CT-DNA pretreated with methylene blue (MB) and the intrinsic fluorescence of BSA through static quenching procedure. Using the binding constant (Kb) obtained from fluorescence studies, thermodynamic parameters (ΔG°, ΔH° and ΔS°) suggested that hydrogen bonding and van der Waals forces, as well as hydrophobic interaction, play the major role between metal complexes with CT-DNA and BSA. In all cases the binding forces were spontaneous owing to -ΔG°.Communicated by Ramaswamy H. Sarma.

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.

Five novel palladium(II) complexes of 8-hydroxyquinoline and amino acids with hydrophobic side chains: synthesis, characterization, cytotoxicity, DNA- and BSA-interaction studies.

The side effects and resistance of metal-based anticancer drugs prompted us to synthesis a novel series of five Pd(II) complexes of the type [Pd(8-QO)(AA)]; where 8-QO = anion of 8-hydroxyquinoline and AA = anions of amino acids having nonpolar aliphatic side chain such as glycine (-H), alanine (-CH3), valine (-CH(CH3)2), leucine (-CH2-CH(CH3)2) and isoleucine (-CH(CH3)CH2-CH3). The complexes have been characterized with the help of FT-IR, UV-Vis, one and two-dimensional 1H-NMR, elemental analysis and conductivity measurements. On the basis of these characterization data, a four coordinated square planar geometry for all of these complexes have been proposed. The compounds were screened for their in vitro activities against human cancer cell line, MOLT-4 and their 50% inhibition concentration were ascertained by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Since four out of the five newly synthesized compounds were found to be more active than the standard anticancer drug, cisplatin, their detailed interaction with calf thymus DNA (as a target) and bovine serum albumin (BSA) (as a carrier) were also carried out by utilizing absorption spectra, fluorescence spectra and ethidium bromide displacement studies. In these experiments, several binding and thermodynamic parameters were also calculated. These results suggested that hydrogen binding and van der Waals forces play a major role in the interaction between metal complexes with CT-DNA and BSA.Communicated by Ramaswamy H. Sarma.

Comparative studies on the interaction between bovine beta-lacto-globulin type A and B and a new designed Pd(II) complex with anti-tumor activity at different temperatures.

An new water-soluble Pd(II) complex, 2,2'-bipyridin n-butyl dithiocarbamato Pd(II) nitrate has been synthesized. The Pd(II) complex has been characterized by elemental analysis and conductivity measurements as well as spectroscopic methods such as infrared, 1H NMR, and ultraviolet-visible. The interaction between this new design Pd(II)-complex, an anti-tumor component, with carrier proteins of beta-lactoglobulin-A and -B (BLG-A and -B) were studied at different temperatures of 27, 37, 42, and 47 degrees C by fluorescence spectroscopy and far-UV circular dichroism (CD) spectrophotometric techniques. A strong fluorescence quenching interaction of Pd(II) complex with BLG-A and -B was observed at different temperatures. The binding parameters were evaluated by fluorescence quenching method. The thermodynamic parameters, including DeltaH degrees , DeltaS degrees , and DeltaG degrees were calculated by fluorescence quenching method indicated that the electrostatic and hydrophobic forces might play a major role in the interactions of Pd(II) complex with BLG-A and -B, respectively. The distances between donors (Trps of the BLG-A and -B) and acceptor (Pd(II) complex) were obtained according to the fluorescence resonance energy transfer (FRET). Far-UV CD studies showed that the Pd(II) complex did not represent any significant changes in the secondary structures of BLG-A and -B. The difference in the interaction properties observed for BLG-A and -B with Pd(II) complex is related to the difference in the amino acid sequences between these two variants.

Nonionic but water soluble, [Glycine-Pd-Alanine] and [Glycine-Pd-Valine] complexes. Their synthesis, characterization, antitumor activities and rich DNA/HSA interaction studies.

Two novel, neutral and water soluble Pd(II) complexes of formula [Pd(Gly)(Ala)] (1) and [Pd(Gly)(Val)] (2) (Gly, Ala, and Val are anionic forms of glycine, alanine, and valine amino acids, respectively) have been synthesized and characterized by FT-IR, UV-Vis, 1H-NMR, elemental analysis, and molar conductivity measurement. The data revealed that each amino acid binds to Pd(II) through the nitrogen of -NH2 and the oxygen of -COO- groups and acts as a bidentate chelate. These complexes have been assayed against leukemia cells (K562) using MTT method. The results indicated that both of the complexes display more cytotoxicity than the well-known anticancer drug, cisplatin. The interaction of the compounds with calf thymus DNA (CT-DNA) and human serum albumin (HSA) were assayed by a series of experimental techniques including electronic absorption, fluorescence, viscometry, gel electrophoresis, and FT-IR. The results indicated that the two complexes have interesting binding propensities toward CT-DNA as well as HSA and the binding affinity of (1) is more than (2). The fluorescence data indicated that both complexes strongly quench the fluorescence of ethidium bromide-DNA system as well as the intrinsic fluorescence of HSA via static quenching procedures. The thermodynamic parameters (ΔH°, ΔS°, and ΔG°) calculated from the fluorescence studies showed that hydrogen bonds and van der Waals interactions play a major role in the binding of the complexes to DNA and HSA. We suggest that both of the Pd(II) complexes exhibit the groove binding mode with CT-DNA and interact with the main binding pocket of HSA. Communicated by Ramaswamy H. Sarma.