Order Of Binding Strength Research Articles

First-principles study of molecular hydrogen binding to heme in competition with O2, NO and CO.

Molecular hydrogen shows antioxidant activity and distinct efficacy towards vascular diseases, but the understanding of this is not yet satisfactory at the atomic level. In this work, we study the binding properties of H2 to the heme group in relation with other diatomic molecules (DMs), including O2, NO and CO, and their displacement reactions, using first-principles calculations. We carry out molecular modeling of the heme group, using iron-porphyrin with the imidazole ligand, i.e., FePIm, and smaller models of Fe(CnHn+2N2)2NH3 with n = 3 and 1, and of molecular complexes of heme-DM and -H. Through analysis of optimized geometries and energetics, it is found that the order of binding strength of DMs or H to the Fe of heme is NO > O2 > CO > H > H2 for FePIm-based systems, while it is H > O2 > NO > CO > H2 for model-based systems. We calculate the activation energies for displacement reactions of H2 and H by other DMs, revealing that the H2 displacements occur spontaneously while the H displacements require a large amount of energy. Finally, our calculations corroborate that the rate constants increase with increasing temperature according to the Arrhenius relation.

DTITR: End-to-end drug–target binding affinity prediction with transformers

The accurate identification of Drug–Target Interactions (DTIs) remains a critical turning point in drug discovery and understanding of the binding process. Despite recent advances in computational solutions to overcome the challenges of in vitro and in vivo experiments, most of the proposed in silico-based methods still focus on binary classification, overlooking the importance of characterizing DTIs with unbiased binding strength values to properly distinguish primary interactions from those with off-targets. Moreover, several of these methods usually simplify the entire interaction mechanism, neglecting the joint contribution of the individual units of each binding component and the interacting substructures involved, and have yet to focus on more explainable and interpretable architectures. In this study, we propose an end-to-end Transformer-based architecture for predicting drug–target binding affinity (DTA) using 1D raw sequential and structural data to represent the proteins and compounds. This architecture exploits self-attention layers to capture the biological and chemical context of the proteins and compounds, respectively, and cross-attention layers to exchange information and capture the pharmacological context of the DTIs. The results show that the proposed architecture is effective in predicting DTA, achieving superior performance in both correctly predicting the value of interaction strength and being able to correctly discriminate the rank order of binding strength compared to state-of-the-art baselines. The combination of multiple Transformer-Encoders was found to result in robust and discriminative aggregate representations of the proteins and compounds for binding affinity prediction, in which the addition of a Cross-Attention Transformer-Encoder was identified as an important block for improving the discriminative power of these representations. Overall, this research study validates the applicability of an end-to-end Transformer-based architecture in the context of drug discovery, capable of self-providing different levels of potential DTI and prediction understanding due to the nature of the attention blocks. The data and source code used in this study are available at: https://github.com/larngroup/DTITR.

Revealing effects of common nonmetallic impurities on the stability and strength of Cu–Sn solder joints: A first-principles investigation

Nonmetallic elements can affect the stability and usability of Cu–Sn solder joints intensively. The electronic structure, adhesion work, and tensile strength of Cu(111)/Cu3Sn(001) interface doping with H, C, O and S have been systematically investigated herein using the first-principles calculations. Cu(Cu)-terminated interface is the most stable among the clean Cu(111)/Cu3Sn(001) interfaces. In the non-metallic atoms doping Cu(111) surface system, H atom tends to occupy tetrahedral interstitial sites, while C, O and S atoms prefer to octahedral interstitial sites. The calculated segregation heat (ΔGseg) indicates that H and O atoms tend to stay in the interior, while C and S atoms tend to segregate to the Cu(111)/Cu3Sn(001) interface. From adhesion works, the order of binding strength is SOct > clean interface > OOct > COct > HTet. Finally, electronic structures of doping systems are analyzed to reveal the effects of nonmetallic impurities on the stability and strength of Cu–Sn solder joints. These results will provide guidance for the design of modified Cu–Sn solder joints.

Effect of Counterion Binding to Swelling of Polyelectrolyte Brushes.

The effect of binding strength of counterions with the polyelectrolyte chain to the swelling of polyelectrolyte brushes is studied, by investigating the swelling of both the polycation and polyanion in response to the variation of the salt concentration under the change of counterion's identity. Two polyelectrolyte brushes grafted on solid substrates are adopted: the cationic poly [2-(methacryloyloxy)ethyltrimethyl ammonium] (PMETA-X, X = F, Cl, Br, and I) and the anionic polystyrene sulfonate (M-PSS, M = Li, Na, K, and Cs). The swelling change with the salt concentration is investigated by ellipsometry, quartz crystal microbalance with dissipation, and dielectric spectroscopy. It is discovered that although the thickness of PMETA-X brushes is larger than that of M-PSS brushes of similar grafting density, the former has much less solvent incorporated than the latter. Such a difference is attributed to the weaker interaction between the PMETA+ chain and its halide counterions than that between the PSS- chain and its alkali counterions, discovered by dielectric spectroscopy. This makes the original charges on the PMETA-X chain less neutralized and therefore have a higher charge density, compared with the M-PSS chain. The results demonstrate that the stronger binding of the counterions to the polyelectrolytes makes the main chains less charged, resulting in the weaker inter-chain electrostatic repulsion and less swelling of the brushes. Investigations into the effect of ion identity show the following order of binding strength: for the cationic PMETA+ chain, F- < Cl- < Br- < I- and for the anionic PSS- chain, Li+ < Na+ < K+ < Cs+.

Intact Transition Epitope Mapping - Thermodynamic Weak-force Order (ITEM - TWO)

We have developed an electrospray mass spectrometry method which is capable to determine antibody affinity in a gas phase experiment. A solution with the immune complex is electrosprayed and multiply charged ions are translated into the gas phase. Then, the intact immune-complex ions are separated from unbound peptide ions. Increasing the voltage difference in a collision cell results in collision induced dissociation of the immune-complex by which bound peptide ions are released. When analyzing a peptide mixture, measuring the mass of the complex-released peptide ions identifies which of the peptides contains the epitope. A step-wise increase in the collision cell voltage difference changes the intensity ratios of the surviving immune complex ions, the released peptide ions, and the antibody ions. From all the ions´ normalized intensity ratios are deduced the thermodynamic quasi equilibrium dissociation constants (KDm0g#) from which are calculated the apparent gas phase Gibbs energies of activation over temperature (ΔGm0g#T). The order of the apparent gas phase dissociation constants of four antibody – epitope peptide pairs matched well with those obtained from in-solution measurements. The determined gas phase values for antibody affinities are independent from the source of the investigated peptides and from the applied instrument. Data are available via ProteomeXchange with identifier PXD016024. SignificanceITEM - TWO enables rapid epitope mapping and determination of apparent dissociation energies of immune complexes with minimal in-solution handling. Mixing of antibody and antigen peptide solutions initiates immune complex formation in solution. Epitope binding strengths are determined in the gas phase after electrospraying the antibody / antigen peptide mixtures and mass spectrometric analysis of immune complexes under different collision induced dissociation conditions. Since the order of binding strengths in the gas phase is the same as that in solution, ITEM – TWO characterizes two most important antibody properties, specificity and affinity.

Non-nucleoside Reverse Transcriptase Inhibitors Inhibit Reverse Transcriptase through a Mutually Exclusive Interaction with Divalent Cation-dNTP Complexes.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are considered noncompetitive inhibitors that structurally alter reverse transcriptase (RT) and dramatically decrease catalysis. In this report, biochemical analysis with various divalent cations was used to demonstrate that NNRTIs and divalent cation-dNTP complexes are mutually exclusive, inhibiting each other's binding to RT/primer/template (RT-P/T) complexes. The binding of catalytically competent divalent cation-dNTP complexes to RT-P/T was measured with Mg2+, Mn2+, Zn2+, Co2+, and Ni2+ using Ca2+, a noncatalytic cation, for displacement. Binding strength order was Mn2+ ≈ Zn2+ ≫ Co2+ > Mg2+ ≈ Ni2+. Consistent with but not exclusive to mutually exclusive binding, primer extension assays showed that stronger divalent cation-dNTP complexes were more resistant to NNRTIs (efavirenz (EFV), rilpivirine (RPV), and nevirapine (NVP)). Filtration assays demonstrated that divalent cation-dNTP complexes inhibited the binding of 14C-labeled EFV to RT-P/T with stronger binding complexes formed with Mn2+ inhibiting more potently than those with Mg2+. Conversely, filter binding assays demonstrated that EFV inhibited 3H-labeled dNTP binding to RT-P/T complexes with displacement of Mn2+-dNTP complexes requiring much greater concentrations of EFV than the more weakly bound Mg2+-dNTP complexes. EFV bound relatively weakly to the NNRTI resistant K103N RT; but, binding was modestly enhanced in the presence of P/T, and EFV was easily displaced by divalent cation-dNTP complexes. This suggests that K103N overcomes EFV inhibition mostly by binding more weakly to the drug and is in contrast to other reports that indicate K103N has little to no effect on drug or dNTP binding. Overall, this biochemical analysis supports recent biophysical analyses of NNRTI-RT interactions that indicate mutually exclusive binding.

On the Power of Geometry over Tetrel Bonds.

Tetrel bonds are noncovalent interactions formed by tetrel atoms (as σ-hole carriers) with a Lewis base. Here, we present a computational and molecular orbital study on the effect of the geometry of the substituents around the tetrel atom on the σ-hole and on the binding strengths. We show that changing the angles between substituents can dramatically increase bond strength. In addition, our findings suggest that the established Sn > Ge > Si order of binding strength can be changed in sufficiently distorted molecules due to the enhancement of the charge transfer component, making silicon the strongest tetrel donor.

DNA Binding Studies and Evaluation of Electrochemical Parameters of New Tri-and Di-Organotin(IV) Complexes of 4-(1H-Indol-3-yl)butanoic Acid

New triorganotin(IV) [R3SnL where R = Me (1), Bu (2), Ph (3)] and diorganotin(IV) [R2SnL2, where R = Me (4), Bu (5), Ph (6)] derivatives of 4-(1H-indol-3-yl)butanoic acid (HL) were prepared and characterized by FT-IR and 1H and 13C NMR spectroscopy. Interaction between DNA and selected compounds was studied by UV-Vis spectroscopy and viscometry. The binding constants calculated on the basis of the accumulated data reveal the following order of binding strength: compound 2 > 1 > 5 > 4. Electrochemical parameters such as diffusion coefficient and charge transfer coefficient are evaluated with cyclic voltammetry. The results demonstrate that diorganotin(IV) complexes are characterized by higher diffusion coefficient than triorganotin(IV) analogues. In case of triorganotin(IV) complexes, the lower coordination number allows a solvent to interact with Sn(IV) center and hence decreases the rate of diffusion.

Isatin based macrocyclic Schiff base ligands as novel candidates for antimicrobial and antioxidant drug design: In vitro DNA binding and biological studies

In the present work, five macrocyclic compounds, C18H12N2O4 (1), C38H24N8O6 (1a), C38H24N8O4S2 (1b), C40H32N8O4 (2a) and C48H32N8O4 (2b) have been synthesized and thoroughly characterized by elemental analysis, FT-IR, 1D & 2D NMR and electron spray ionization mass spectral analysis. The DNA binding ability of these compounds were investigated in vitro by UV–Visible, fluorescence, circular dichroism (CD) spectroscopy and viscosity measurements. The results indicate that these compounds possess strong DNA binding affinity via intercalation, while the order of binding strength followed the trend 2b (1.52 ± 0.06 × 105 M−1) > 2a (1.12 ± 0.11 × 105 M−1) > 1b (1.05 ± 0.04 × 105 M−1) > 1a (0.97 ± 0.14 × 104 M−1) > 1 (0.75 ± 0.21 × 104 M−1). The radical scavenging potencies of the compounds were explored by employing DPPH, OH and NO assays, in which 1a exhibited highest inhibitory effect on the radicals (IC50 = 23.59 μM (DPPH), 26.14 μM (OH), 28.41 μM (NO)). The in vitro antibacterial studies showed that these compounds have the potential to arrest the growth of bacteria, among which, 1a was found to be vulnerable against the bacterial stains. In addition, in silico molecular docking stimulations were also performed to position these compounds into the active sites of bacterial membrane proteins. The results of in vitro and in silico investigations reveal that the compounds apprehend the bacterial growth significantly. The data obtained from this piece of work would be helpful to design antibacterial drugs incorporating isatin based macrocyclic frameworks.

The behaviors of helium atoms in tantalum, rhenium and osmium

We present systematic first-principles studies of occupancy, diffusion, and segregation of He atoms, as well as underlying evolution mechanism of He clusters in Ta, Re and Os to compare to that in W. It is found that single interstitial He atom prefers tetrahedral (T) site in Ta and W and basal octahedral (BO) site in Re and Os. Single He atom prefers the diffusion path from one T site to the closest T site in Ta and W, and the diffusion path from one BO site to the next BO site passing an octahedral site along 〈0001〉 direction in Re and Os. The diffusion of single He atom in Ta, Re and Os is relatively difficult than that in W. He atoms are energetically favorable to segregate at interstitial sites forming Hen clusters in Ta, W, Re and Os, and form close-packed He monolayer structure between (110) planes in Ta and W. The binding strength of Hen cluster in Ta, Re and Os is relatively small than that in W (W>Os>Re>Ta). Compared to interstitial sites, He atoms are more energetically favorable to aggregate in vacancy cluster forming VacmHen. The binding strength order of VacmHen cluster in the systems obeys W≃Os>Re>Ta.

Comprehensive View of the Ligand–Gold Interface from First Principles

A large number of ligands have been used to stabilize and functionalize the gold surfaces and nanoclusters, but there has been no systematic comparison about their binding strengths with gold. In this work, we studied the interaction between 27 ligands of six different types (thiolates, phosphines, amines, aryl radicals, alkynyls, and N-heterocyclic carbenes) with the model Au surfaces by first-principles density functional theory (DFT). On the perfect Au(111), we found the order of binding strengths to be bulky N-heterocyclic carbenes (NHCs) ≈ alkynyls > thiolates ≈ phosphines > aryls ≈ less sterically bulky NHCs > alkylamines. The much stronger interaction of bulky carbenes to Au than the less sterically bulky NHCs arises from the van der Waals (vdW) attraction of bulky side groups with gold surface via the short Au···HCH2R contact. Further, we showed that the presence of a gold adatom on Au(111) leads to enhanced binding and a similar order for most of the ligands examined. Overall, bulky NHCs and alky...

Development of a ReaxFF Reactive Force Field for the Pt-Ni Alloy Catalyst.

We developed the ReaxFF force field for Pt/Ni/C/H/O interactions, specifically targeted for heterogeneous catalysis application of the Pt-Ni alloy. The force field is trained using the DFT data for equations of state of Pt3Ni, PtNi3 and PtNi alloys, the surface energy of the PtxNi1-x(111) (x = 0.67-0.83), and binding energies of various atomic and molecular species (O, H, C, CH, CH2, CH3, CO, OH, and H2O) on these surfaces. The ReaxFF force field shows a Pt surface segregation at x ≥ 0.67 for the (111) surface and x ≥ 0.62 for the (100) surface in vacuum. In addition, from the investigation of the preferential alloy component of the adsorbates, it is expected that H and CH3 on the alloy surface to induce a segregation of Pt whereas the oxidation intermediates and products such as C, O, OH, H2O, CO, CH, and CH2 are found to induce Ni segregation. The relative order of binding strengths among adsorbates is a function of alloy composition and the force field is trained to describe the trend observed in DFT calculations, namely, H2 < H2O < CH3 ≈ O2 ≈ CO < OH < CH2 < C ≈ CH on Pt8Ni4, H2 < H2O < CO ≈ O2 < CH3 < OH < CH2 < CH < C on Pt9Ni3, and H2 < H2O < O2 < CO < CH3 < OH < CH2 < C ≈ CH on Pt10Ni2. Using this force field, we performed the grand-canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulations for a Pt3Ni slab and a truncated cuboctahedral nanoparticle terminated by (111) and (100) faces, to examine the surface segregation trend under different gas environments. It is found that Pt segregates to the alloy surface when the surface is exposed to vacuum and/or H2 environment while Ni segregates under the O2 environment. These results suggest that the Pt/Ni alloy force field can be successfully used for the preparation of Pt-Ni nanobimetallic catalysts structure using GCMC and run MD simulations to investigate its role and the catalytic chemistry in catalytic oxidation, dehydrogenation and coupling reactions. The current Pt/Ni force field still is found to have difficulties in describing the observed segregation trend in Ni-rich alloy compositions (x < 0.6), suggesting the need for additional force field training and evaluation for its application to describe the characteristics and chemistry of Ni-rich alloys.

Novel Bioactive Co(II), Cu(II), Ni(II) and Zn(II) Complexes with Schiff Base Ligand Derived from Histidine and 1,3-Indandione: Synthesis, Structural Elucidation, Biological Investigation and Docking Analysis.

Novel bioactive complexes of Co(II), Cu(II), Ni(II) and Zn(II) metal ions with Schiff base ligand derived from histidine and 1,3-indandione were synthesized and thoroughly characterized by various analytical and spectral techniques. The biological investigations were carried out to examine the efficiency of the binding interaction of all the complexes with calf thymus DNA (CT-DNA). The binding properties were studied and evaluated quantitatively by Kb and Ksq values using UV-visible, fluorescence spectroscopy and voltammetric techniques. The experimental results revealed that the mode of binding of all the complexes with CT-DNA is via intercalation. It is further verified by viscosity measurements and thermal denaturation experiments. From the results of the cleavage study with pUC19 DNA it is inferred that all the complexes possess excellent cleaving ability. The present investigation proved that the binding interaction of all the complexes are significantly strong and the order of binding strength of the complexes is [Ni(L)2] (Kb=3.11×106M-1)>[Co(L)2] (Kb=2.89×106M-1)>[Cu(L)2] (Kb=2.64×106M-1)>[Zn(L)2] (Kb=2.41×105M-1). The complexes were also screened for antibacterial and anticandidal activity. The in vitro cytotoxicity of the ligand and complexes on the NIH/3T3 mouse fibroblast cell lines were examined using CellTiter-Blue® (CTB) Cell viability assay, which unveiled that all the complexes exhibit more potent activities against NIH/3T3 cells. Among all the complexes [Zn(L)2] complex showed the maximum efficiency.

Adsorption of Carbon Dioxide on Unsaturated Metal Sites in M2(dobpdc) Frameworks with Exceptional Structural Stability and Relation between Lewis Acidity and Adsorption Enthalpy

A series of metal-organic frameworks (MOFs) M2 (dobpdc) (M=Mn, Co, Ni, Zn; H4 dobpdc=4,4'-dihydroxy-1,1'-biphenyl-3,3'-dicarboxylic acid), with a highly dense arrangement of open metal sites along hexagonal channels were prepared by microwave-assisted or simple solvothermal reactions. The activated materials were structurally expanded when guest molecules including CO2 were introduced into the pores. The Lewis acidity of the open metal sites varied in the order Mn<Co<Ni>Zn, as confirmed by C=O stretching bands in the IR spectra, which are related to the CO2 adsorption enthalpy. DFT calculations revealed that the high CO2 binding affinity of transition-metal-based M2 (dobpdc) is primarily attributable to the favorable charge transfer from CO2 (oxygen lone pair acting as a Lewis base) to the open metal sites (Lewis acid), while electrostatic effects, the underlying factor responsible for the particular order of binding strength observed across different transition metals, also play a role. The framework stability against water coincides with the order of Lewis acidity. In this series of MOFs, the structural stability of Ni2 (dobpdc) is exceptional; it endured in water vapor, liquid water, and in refluxing water for one month, and the solid remained intact on exposure to solutions of pH 2-13. The DFT calculations also support the experimental finding that Ni2 (dobpdc) has higher chemical stability than the other frameworks.

Spectroscopic analyses on interaction of melamine, cyanuric acid and uric acid with DNA

In this work, the interaction of DNA with melamine (MEL), cyanuric acid (CYA) and uric acid (UA) were studied, respectively, by means of UV–vis, fluorescence, circular dichroism (CD) spectroscopy, viscosity and gel electrophoresis methods. The fluorescence quenching was used to study the interaction models of MEL, CYA and UA with DNA, respectively, and the bimolecular quenching constant (Kq), apparent quenching constant (Ksv), effective binding constant (KA) and corresponding dissociation constant (KD) and binding site number (n) were calculated by adopting Stern–Volmer, Lineweaver–Burk and Double logarithm equations. The results show that MEL, CYA and UA are all able to markedly bind to DNA, and the binding strength order is DNA–UA>DNA–CYA>DNA–MEL. It is wished that these researches would facilitate the understanding of the formation of kidney stones and gout in the body after ingesting excess MEL.

Antibody mediated rejection of renal transplantation – Clinicopathological correlation

Immobilized metal affinity membranes (IMAMs) were prepared by immobilizing copper ions on microporous regenerated cellulose membranes through different types of chelating agents (dentate and triazine dye). The resulting chelator utilization percentages were 95% for iminodiacetic acid, 56% for N,N,N-tris(carboxymethyl)ethylenediamine, 52% for Cibacron blue 3GA, and 140% for Cibacron red 3BA. On the other hand, triazine dyes were slightly superior to dentate chelators on metal ion utilization for protein adsorption. In batch single-protein adsorptions, the protein adsorption capacity decreased with increasing molecular size and number of accessible surface histidine residues [lysozyme>bovine serum albumin (BSA)>γ-globulin], while the binding strength order was the opposite (γ-globulin>BSA>lysozyme). Moreover, the proportions of specific and nonspecific bindings were evaluated by varying pH and salt concentration conditions. A large fraction of the adsorption capacity was found to come from the nonspecific interactions for the prepared IMAMs. Lastly, batch three-protein adsorptions were performed and weak adsorption competition was observed.

Spectroscopic analyses and studies on respective interaction of cyanuric acid and uric acid with bovine serum albumin and melamine

In this work, the fluorescence quenching was used to study the interaction of cyanuric acid (CYA) and uric acid (UA) with bovine serum albumin (BSA) at two different temperatures (283K and 310K). The bimolecular quenching constant (Kq), apparent quenching constant (Ksv), effective binding constant (KA) and corresponding dissociation constant (KD), binding site number (n) and binding distance (r) were calculated by adopting Stern–Volmer, Lineweaver–Burk, Double logarithm and overlap integral equations. The results show that CYA and UA are both able to obviously bind to BSA, but the binding strength order is BSA+CYA<BSA+UA. And then, the interactions of CYA and UA with melamine (MEL) under the same conditions were also studied by using similar methods. The results indicates that both CYA and UA can bind together closely with melamine (MEL). It is wished that these research results would facilitate the understanding the formation of kidney stones and gout in the body after ingesting excess MEL.

The Synergetic Interplay of Weak Interactions in the Ion‐Pair Recognition of Quaternary and Diquaternary Ammonium Salts by Halogenated Resorcinarenes

AbstractThe influence of halogens on the noncovalent interactions of different upper‐rim‐substituted hexylresorcinarenes with quaternary and diquaternary ammonium iodide salts was investigated in the gas phase by electrospray ionization Fourier‐transform ion‐cyclotron‐resonance (ESI‐FTICR) mass spectrometry and in solution by 1H NMR titration studies. The electronic nature of the substituents on the upper rim of the resorcinarene was directly reflected in the order of binding strengths of the hosts towards quaternary and diquaternary ammonium cations in the gas phase. In solution, the opposite trend was observed, with generally higher binding constants for the diquaternary over the quaternary salts. This phenomenon is explained by the synergetic effect originating from the interaction of the halogenated resorcinarenes with the counteranions through enhanced hydrogen bonding, leading to ion‐pair binding in solution. The electronegativity of the halogens renders the hydrogen of the hydroxy group more acidic, and hence enforces hydrogen bonding in solution. The collective effect of several weak interactions is manifested in solution, thereby emphasizing the benefits of comparing solution and gas‐phase studies in recognition processes.

Polymer–cobalt(III) complexes: structural analysis of metal chelates on DNA interaction and comparative cytotoxic activity

A new series of pendant-type polymer-cobalt(III) complexes, [Co(LL)2(BPEI)Cl]2+, (where BPEI = branched polyethyleneimine, LL = dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro)phenazine (dpqc), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq) and imidazo[4,5-f]1,10-phenanthroline (ip)) each with three different degrees of coordination have been synthesized and characterized. Studies to know the mode and strength of interaction between these polymer–metal complexes and calf thymus DNA have been performed by UV–Visible absorption and emission techniques. Among these series, each polymer metal complex having higher binding strength with DNA has been selected to test against human cancer/normal cell lines. On the basis of these spectral studies, it is proposed that our polymer–metal complexes bind with DNA mainly through intercalation along with some electrostatic binding. The order of binding strength for the complexes with ligand, dpqc > dpq > ip. The analysis of the results suggests that polymer–cobalt(III) complexes with higher degree of coordination effectively binds with DNA due to the presence of large number of positively charged cobalt(III) chelates in the polymer chain which cooperatively act to increase the overall binding strength. These polymer–cobalt(III) complexes with hydrophobic ligands around the cobalt(III) metal centre favour the base stacking interactions via intercalation. All the complexes show very good anticancer activities and increasing of binding strength results in higher inhibition value. The polymer–cobalt(III) complex with dpqc ligand possess two fold increased anticancer activity when compared to complexes with other ligands against MCF-7 cells. Besides, the complexes were insensitive towards the growth of normal cells (HEK-293) at the IC50 concentration.

Characterization and DNA binding studies of unexplored imidazolidines by electronic absorption spectroscopy and cyclic voltammetry

UV–Vis spectroscopic behavior of four imidazolidine derivatives i.e., [5-benzylideneimidazolidine-2,4-dione (NBI), 5-(2-hydroxybenzylidene)imidazolidine-2,4-dione (HBI), 5-(4-methoxybenzylidene)imidazolidine-2,4-dione (MBI) and 5-(3,4-di-methoxybenzylidene)imidazolidine-2,4-dione (DBI)] was studied in a wide pH range. Spectroscopic response of the studied compounds was found sensitive to pH and the attached substituents. Incited by anti-tumor activity, structural miscellany and biological applications of imidazolidines, the DNA binding affinity of some novel derivatives of this class of compounds was examined by cyclic voltammetry (CV) and UV–Vis spectroscopy at pH values of blood (7.4) and lysosomes (4.5). The CV results showed the following order of binding strength: KNBI (6.40×106M−1)>KHBI (1.77×105M−1)>KMBI (2.06×104M−1)>KDBI (1.01×104M−1) at pH 7.4. The same order was also obtained from UV–Vis spectroscopy. The greater affinity of NBI justified its preferred candidature as an effective anti-cancer drug. The DNA binding propensity of these compounds was found comparable or greater than most of the clinically used anticancer drugs.