DNA Docking Studies Research Articles

Synthesis, spectroscopic characterization, crystal structure and DNA docking studies of a new trans-platinum saccharinate complex containing aqua and dimethyl sulfoxide ligands

A new trans-platinum complex, trans-[Pt(sac)2(H2O)(DMSO)] (sac= saccharinate; DMSO= dimethyl sulfoxide), was synthesized and characterized by elemental analysis, UV, FTIR, NMR spectroscopy and X-ray single-crystal diffraction. In the mononuclear complex, the platinum(II) cation was coordinated by two N-coordinated sac ligands in the trans position, the sulfur atom of the DMSO ligand, and an aqua ligand, forming a distorted square planar coordination geometry. The interaction of the platinum(II) complex with DNA was studied using molecular docking. The complex successively docked into the minor groove of DNA via intermolecular hydrogen bonds with the adenine, cytosine, and guanine bases.

Anti-enzymatic and DNA docking studies of montelukast: A multifaceted molecular scaffold with in vitro investigations, molecular expression analysis and molecular dynamics simulations

Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the present studies, montelukast was subjected to in vitro inhibitory assays followed by kinetic and in silico investigations. Montelukast demonstrated inhibitory activity against yeast α-glucosidase (IC50 44.31 ± 1.21 μM), jack bean urease (JB urease, IC50 8.72 ± 0.23 μM), human placental alkaline phosphatase (hPAP, IC50 17.53 ± 0.19 μM), bovine intestinal alkaline phosphatase (bIAP, IC50 15.18 ± 0.23 μM) and soybean 15-lipoxygenase (15-LOX, IC50 2.41 ± 0.13 μM). Kinetic studies against α-glucosidase and urease enzymes revealed its competitive mode of inhibition. Molecular expression analysis of montelukast in breast cancer cell line MCF-7 down-regulated AP by a factor of 0.27 (5 μM) compared with the 0.26 value for standard inhibitor levamisole (10 μM). Molecular docking estimated a binding affinity ranging −8.82 to −15.65 kcal/mol for the enzymes. Docking against the DNA dodecamer (ID: 1BNA) observed −9.13 kcal/mol via minor groove binding. MD simulations suggested stable binding between montelukast and the target proteins predicting strong inhibitory potential of the ligand. Montelukast features a chloroquinoline, phenyl ring, a cyclopropane group, a carboxylic group and a sulfur atom all of which collectively enhance its inhibitory potential against the said enzymes. These in vitro and computational investigations demonstrate that it is possible and suggested that the interactions of montelukast with more than one targets presented herein may be linked with the side effects presented by this drug and necessitate additional work. The results altogether suggest montelukast as an important structural scaffold possessing multitargeted features and warrant further investigations in repurposing beyond its traditional pharmacological use.

Sensor properties of heterocyclic compound with nanoparticles – molecular docking studies

Quenching and enhancing behaviour of 1-(4-methoxyphenyl)-2-(4-methylnaphthalen-1-yl)-1H-phenanthro[9,10-d]imidazole (MMPI) with Cu –doped ZnO nanoparticle has been studied. MMPI has been characterized by 1H, 13C NMR and mass spectral analysis. Cu –doped ZnO nanoparticle have been synthesised by sol-gel method and characterized by powder X-ray diffraction (XRD), Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectra (EDS). Quenching and enhancing behaviour were confirmed by the MMPI strongly binding on the surface of Cu –doped ZnO nanoparticle. Increasing concentration of nanoparticle into MMPI results in enhances absorbance and quenching fluorescence was observed. Fluorescence quenching was confirmed electron transfer from excited state of MMPI to nanoparticle. Theoretical calculations were performed by Gaussian -03 package. In order to understand the binding interaction with DNA docking study has been carried out.

Supramolecular Assembly of a Terpyridyl based Binuclear Cu(II) Complex and its DNA Docking Study

ABSTRACT A terpyridyl-based binuclear Cu(II) complex, formulated as [Cu2(tpy)2(muco)(NO3)2], (1) (typ = 2,2’;6’,2”-terpyridine and H2-muco = trans, trans-muconic acid) was synthesised in a single pot technique using slow evaporation method. Blue coloured distorted octahedral-shaped crystals were obtained after a day. Synthesised compound has been characterised by elemental analysis as well as single crystal X-ray diffraction (SCXRD) techniques. Hirshfeld surface analysis has been explored to check out the nature of intermolecular interactions and packing modes of compounds in the crystalline state. From the docking study, it has been found that the metal complex bind to the major groove of DNA and the planner aromatic pyridine ring of the ligand partially intercalate into the base pairs.

Synthesis, spectroscopic and biological activity evaluation of Ni(II), Cu(II) and Zn(II) complexes of schiff base derived from pyridoxal and 4-fluorobenzohydrazide

A novel Schiff base ligand, 4-fluoro-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)benzohydrazide (PLFBH) was synthesized by condensationof pyridoxal and 4-fluorobenzohydrazide. Its complexes with Ni(II), Cu(II), and Zn(II) metal ionswere prepared and characterized by spectroscopic IR, 1H-NMR, UV, LC-MS, ESR, and powder XRD studies and by elemental analysis and thermal analysis, molar conductance, and magnetic susceptibility measurements. The results indicate the geometry of the complexes to be hexa coordinate distorted octahedral. Based on the electronic absorption and fluorescence emission spectra and viscosity studies, an intercalative mode of binding of the complexes with CT-DNA was suggested, which was also supported by DNA docking studies. The docking studies of metal complexes with DNA were carried out using Autodock 4.2. The in vitro anticancer assay for the Cu(II)-PLFBH complex was performed to assess the ability of the complex to inhibit human cell proliferation on HeLa human cervical carcinoma cells, MCF-7 human breast carcinoma cells, and A549 human lung carcinoma cells. The Cu(II)-PLFBH complex exhibited moderate to good inhibitory effect on the cancer cell lines studied. The complexes showed good cleavageability toward plasmid pBR322 DNA. The metal complexes were found to show good antibacterial activity against gram positive bacteria, Staphylococcus aureus and Bacillus cereus and gram negative bacteria Escherichia coli and Pseudomonas aeruginosa cultures,while the ligand showed marginal activity. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1961271 .

Retraction Note to: Site Specific Interaction Between TiO2 Nanoparticles and Phenanthrimidazole-A First Principles Quantum Mechanical Study.

Understanding the interaction between the nanomaterials and bioactive molecules are of current interest due to the potential application of nanomaterial in biomedical field. The structural, electronic and optical properties of newly synthesised fluorophore 2-(4-methoxynaphthalen-1-yl)-1-phenyl-1H-phenanthro[9.10-d]imidazole have been investigated in detail. The imidazole absorbs strongly on the surface of TiO2 nanocrystals probably because of the chemical affinity of azomethine nitrogen atom of the imidazole, resulting in lowering the HOMO and LUMO energy levels. The TEM, SEM and EDX spectra confirm the adsorption of imidazole on the surface of TiO2 nanocrystals. The growth behavior and stability of small stoichiometric (TiO2)n clusters have been analysed by using density functional theory which reveals that clusters prefers three-dimensional structures. In addition, the interaction between the ground state structure of the (TiO2)n cluster and a single imidazole molecule have been studied. The calculated binding energy (Eb) and the energy gap (Eg) indicate that the imidazole molecule preferably binds to the Ti atom of the (TiO2)n clusters through its azomethine nitrogen atom; the binding energy is in range 5.24–7.89 eV. In order to understand the binding interaction with DNA docking study has been carried out.

Bis- and mixed-ligand copper(II) complexes of nalidixic acid the antibacterial drug: Mode of nalidixate coordination determines DNA binding and cleavage and cytotoxicity

The new complexes [Cu(nal)2]∙2H2O 1 and [Cu(en)2(nal)2] 2, where H(nal) is the antibacterial drug nalidixic acid, have been isolated and their X-ray structures successfully determined. The complex 1 possesses a square planar CuO4 chromophore constituted by the pyridone and carboxylate oxygen atoms of nalidixate anion. Complex 2 contains a CuN4O2 chromophore with a tetragonally distorted octahedral geometry, and the trans-axial coordination of two nalidixate anions at longer distances to the CuN4 plane constituted by ethylenediamine is stabilized by a network of H-bonding. DFT studies illustrate the structures and stabilities of complexes. The DNA binding affinity of 2 (Kb, 9.2 (±0.2) × 104 M−1) is higher than that of [Cu(en)2]2+ [Kb, 2.0 (±0.2) × 104 M−1], illustrating that bound nal¯ enhances the DNA binding affinity. DNA docking studies reveal that 2 bound to DNA undergoes interesting coordinative distortions more than 1, causing more significant changes in DNA host. Thus, 2 displays oxidative DNA cleavage (ascorbic acid) more prominent than [Cu(en)2]2+, by generating OH radicals, and shows poor cytotoxicity towards A549 lung cancer cell lines.

Synthesis, reactivity, X-ray characterization and docking studies of N7/N9-(2-pyrimidyl)-adenine derivatives

The reaction of adenine with 2-chloropyrimidine yields as a major product the unexpected N7-(2-pyrimidyl)-adenine (1) and as a minor one N9-(2-pyrimidyl)-adenine (2). Both compounds have been characterized by X-ray diffraction analysis. Moreover, we report the formation of a 1:1 co-crystal (3) composed by compound (1) and adenine that was formed serendipitously during the synthesis of (1). Unexpectedly, the treatment of (1) with Brönsted acids like HCl or HNO3 causes the opening of the imidazole ring of the N7-substituted adenine, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine (4–7) which we have X-ray characterized in its neutral, (4), monoprotonated [nitrate salt (6)] and diprotonated forms [hydrochloride salt (5) and, also, a tetrachlorozincate salt (7)]. Finally, we have used compound (5) as ligand to synthesize and X-ray characterize its complexes with Ir(III) and Ag(I) (compounds (8) and (9), respectively), where the latter is a 2D coordination polymer and the former is a discrete mononuclear complex. We have studied the supramolecular assemblies formed in the solid state by using density functional theory (DFT) calculations. Finally, DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA.

Radicalic cleavage pathway and DNA docking studies of novel chemotherapic platinum agent of 5,6-di-2-ithienyl-2,3-dihydropyrazine

A new Pt(II) complex of the general formula ([PtCl2(L)]·H2O), where L is 5,6-di-2-thienyl-2,3-dihydropyrazine is synthesized as a potential antitumor agent and its structure is elucidated using a variety of physical and chemical procedures. DNA attaching ability of the complex is studied spectroscopically. UV and fluorometric titration, viscometric measurements and thermal decomposition studies agreed that two binding mode of actions, covalent and non-covalent bindings, are possible simultaneously. DNA helix cleavage studies clearly indicated OH• radical pathway in the presence of the reducing agent. Quantum mechanical calculations are carried out to call the minimum energy structures of the ligand and the complex, and to determine the FTIR, 1H NMR and UV–Vis spectra using the density functional theory (DFT) at the B3LYP/LANL2DZ level of theory. Calculated geometrical parameters for the complex indicated a square-planar structure around the metallic center through the dithiopyridyl ring and two chlorine atoms. The minimum energy structure of the complex obtained from DFT conformational analysis is used in docking studies to investigate complex-DNA binding mechanisms. The complex interacts with DNA through three different mechanisms, namely, intercalation, covalent and electrostatic interaction. The most stable mode of interaction with lowest binding energy (–333.6 kcal/mol) was intercalation mode. Comparisons between theoretical and experimental findings are performed and a good agreement is obtained.

Competitive binding affinity of two lanthanum(III) macrocycle complexes toward DNA and bovine serum albumin in water

In the present study, two water-soluble lanthanum(III) hexaaza Schiff base complexes were synthesized and characterized and also theoretically investigated. The interactions of these complexes with DNA and bovine serum albumin (BSA) were studied using different spectroscopic assessments and docking simulation analysis. The DNA docking studies suggested that these two complexes are able to interact with DNA through the minor groove, and also the binding affinity is in the order of La(L1) > La(L2). Furthermore, the spectral titration was carried out and viscosity measurements were taken. In this regard, protein-binding studies revealed that these complexes quench the intrinsic fluorescence of BSA, and indicated that the possible binding site is located on the vicinity of Trp 213, which is further validated by docking simulation analysis. The in vitro anticancer activities of these complexes indicated that the La(L1) complex is more effective than the other one and also exhibits a better interaction with DNA.

DNA and protein binding, double-strand DNA cleavage and cytotoxicity of mixed ligand copper(II) complexes of the antibacterial drug nalidixic acid

The water soluble mixed ligand complexes [Cu(nal)(diimine)(H2O)](ClO4) 1–4, where H(nal) is nalidixic acid and diimine is 2,2′-bipyridine (1), 1,10-phenanthroline (2), 5,6-dimethyl-1,10-phenanthroline (3), and 3,4,7,8-tetramethyl-1,10-phenanthroline (4), have been isolated. The coordination geometry around Cu(II) in 1 and that in the Density Functional Theory optimized structures of 1–4 has been assessed as square pyramidal. The trend in DNA binding constants (Kb) determined using absorption spectral titration (Kb: 1, 0.79±0.1<2, 1.06±0.1<3, 1.79±0.2<4, 1.84±0.2×105M−1) is in line with that (Kapp) determined by competitive ethidium bromide binding studies. The large red-shift (10nm) observed for 2 suggests that the phen co-ligand is stacked with a frayed DNA base pair. In contrast, 3 and 4 are involved in intimate hydrophobic interaction with DNA through the methyl substituents on phen ring, which is supported by viscosity and protein binding studies. DNA docking studies imply that 4 is involved preferentially in DNA major groove binding while 1–3 in minor groove binding and that all the complexes, upon removing the axially coordinated water molecule, bind in the major groove. Interestingly, 3 and 4 display prominent double-strand DNA cleavage while 1 and 2 effect only single-strand DNA cleavage in the absence of an activator. The complexes 3 and 4 show cytotoxicity higher than 1 and 2 against human breast cancer cell lines (MCF-7). The complex 4 induces apoptotic mode of cell death in cancer cells.

Investigation of the complex structure, comparative DNA-binding and DNA cleavage of two water-soluble mono-nuclear lanthanum(III) complexes and cytotoxic activity of chitosan-coated magnetic nanoparticles as drug delivery for the complexes

Two water-soluble mono-nuclear macrocyclic lanthanum(III) complexes of 2,6-diformyl-4-methylphenol with 1,3-diamino-2-propanol (C1) or 1,3-propylenediamine (C2) were synthesized and characterized by UV–Vis, FT-IR, 13C and 1H NMR spectroscopy and elemental analysis. C1 complex was structurally characterized by single-crystal X-ray diffraction, which revealed that the complex was mononuclear and ten-coordinated. The coordination sites around lanthanum(III) were occupied with a five-dentate ligand, two bidentate nitrates, and one water molecule. The interaction of complexes with DNA was studied in buffered aqueous solution at pH7.4. UV–Vis absorption spectroscopy, emission spectroscopy, circular dichroism (CD) and viscometric measurements provided clear evidence of the intercalation mechanism of binding. The obtained intrinsic binding constants (Kb) 9.3×103 and 1.2×103M−1 for C1 and C2, respectively confirmed that C1 is better intercalator than C2. The DNA docking studies suggested that the complexes bind with DNA in a groove binding mode with the binding affinity of C1>C2. Moreover, agarose gel electrophoresis study of the DNA-complex for both compounds revealed that the C1 intercalation cause ethidium bromide replacement in a competitive manner which confirms the suggested mechanism of binding. Finally, the anticancer experiments for the treated cancerous cell lines with both synthesized compounds show that these hydrophilic molecules need a suitable carrier to pass through the hydrophobic nature of cell membrane efficiently.

Site Specific Interaction Between TiO2 Nanoparticles and Phenanthrimidazole-A First Principles Quantum Mechanical Study.

Understanding the interaction between the nanomaterials and bioactive molecules are of current interest due to the potential application of nanomaterial in biomedical field. The structural, electronic and optical properties of newly synthesised fluorophore 2-(4-methoxynaphthalen-1-yl)-1-phenyl-1H-phenanthro[9.10-d]imidazole have been investigated in detail. The imidazole absorbs strongly on the surface of TiO2 nanocrystals probably because of the chemical affinity of azomethine nitrogen atom of the imidazole, resulting in lowering the HOMO and LUMO energy levels. The TEM, SEM and EDX spectra confirm the adsorption of imidazole on the surface of TiO2 nanocrystals. The growth behavior and stability of small stoichiometric (TiO2)n clusters have been analysed by using density functional theory which reveals that clusters prefers three-dimensional structures. In addition, the interaction between the ground state structure of the (TiO2)n cluster and a single imidazole molecule have been studied. The calculated binding energy (Eb) and the energy gap (Eg) indicate that the imidazole molecule preferably binds to the Ti atom of the (TiO2)n clusters through its azomethine nitrogen atom; the binding energy is in range 5.24-7.89 eV. In order to understand the binding interaction with DNA docking study has been carried out.

Enhancing photoresponse of ionic liquid–ZnO composite: Molecular docking study

Influence of the size of nanocrystalline ZnO on the emission of white light from ionic liquid, 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (cationic IL) has been studied. Increase of crystalline size of ZnO decrease the shift of absorption edge due to semiconductor–ionic liquid interaction. The wavelength of green as well as blue emissions are increased on increasing the size of the nanocrystal. This is likely to be because of the increase of band gap energy of the semiconductor on decrease of the crystal size. In order to understand the binding interaction with DNA docking study has been carried out.

Synthesis, structure and molecular docking studies of dicopper(ii) complexes bridged by N-phenolato-N′-[2-(dimethylamino)ethyl]oxamide: the influence of terminal ligands on cytotoxicity and reactivity towards DNA and protein BSA

Two dicopper(II) complexes bridged by N-phenolato-N′-[2-(dimethylamino)ethyl]oxamide (H3pdmaeox) and end-capped with 2,2′-diamino-4,4′-bithiazole (dabt) and 2,2′-bipyridine (bpy), respectively, namely [Cu2(pdmaeox)Cl(CH3OH)(dabt)]·CH3OH (1) and [Cu2(pdmaeox)(bpy)(H2O)]-(pic)·H2O (2) (where pic− denotes the picrate anion) have been synthesized. Complex 1 was characterized by elemental analysis, molar conductivity measurements, IR and electronic spectral studies, and single-crystal X-ray diffraction. The crystal structure analyses reveal that the dissymmetric unit of complex 1 contains a neutral dicopper(II) complex moiety [Cu2(pdmaeox)Cl-(CH3OH)(dabt)], in which the cis-pdmaeox3− ligand bridges two copper(II) ions with the separation of 5.2238(19) A. Through hydrogen bonding interactions, complex 1 molecules are assembled into 3D supramolecular structures. The structure and DNA-binding activities of complex 2 have been reported in our previous paper. However, its other properties were not studied. In order to gain some insight into the structure–activity relationship, the reactivities towards DNA and protein of the two dicopper(II) complexes are studied both theoretically and experimentally. The DNA docking study suggests that all the two dicopper(II) complexes can interact with DNA through the minor groove, and the binding affinity follows the order of 1 > 2, which is further validated by spectral titration, electrochemical techniques, and viscosity measurements. Bovine serum albumin (BSA) binding activity studies revealed that the two dicopper(II) complexes can strongly quench the intrinsic fluorescence of BSA through a static quenching mechanism with the ratio of the dicopper(II) complex to BSA being 1 : 1, and the most possible binding site is in the proximity of Trp134. The in vitro anticancer activities indicate that the two dicopper(II) complexes are active against the selected tumor cell lines, and the order of in vitro anticancer activities is consistent with the DNA-binding affinities. The influence of structural variation of the terminal ligands in the dicopper(II) complexes on DNA-binding modes and anticancer activities is preliminarily discussed.

Ruthenium–Arene Complexes of Curcumin: X-Ray and Density Functional Theory Structure, Synthesis, and Spectroscopic Characterization, in Vitro Antitumor Activity, and DNA Docking Studies of (p-Cymene)Ru(curcuminato)chloro

The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC(50) = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxy-curcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20° between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.

Scoring function for DNA–drug docking of anticancer and antiparasitic compounds based on spectral moments of 2D lattice graphs for molecular dynamics trajectories

We introduce here a new class of invariants for MD trajectories based on the spectral moments π k (L) of the Markov matrix associated to lattice network-like (LN) graph representations of Molecular Dynamics (MD) trajectories. The procedure embeds the MD energy profiles on a 2D Cartesian coordinates system using simple heuristic rules. At the same time, we associate the LN with a Markov matrix that describes the probabilities of passing from one state to other in the new 2D space. We construct this type of LNs for 422 MD trajectories obtained in DNA–drug docking experiments of 57 furocoumarins. The combined use of psoralens + ultraviolet light (UVA) radiation is known as PUVA therapy. PUVA is effective in the treatment of skin diseases such as psoriasis and mycosis fungoides. PUVA is also useful to treat human platelet (PTL) concentrates in order to eliminate Leishmania spp. and Trypanosoma cruzi. Both are parasites that cause Leishmaniosis (a dangerous skin and visceral disease) and Chagas disease, respectively; and may circulate in blood products collected from infected donors. We included in this study both lineal (psoralens) and angular (angelicins) furocoumarins. In the study, we grouped the LNs on two sets; set1: DNA–drug complex MD trajectories for active compounds and set2: MD trajectories of non-active compounds or no-optimal MD trajectories of active compounds. We calculated the respective π k (L) values for all these LNs and used them as inputs to train a new classifier that discriminate set1 from set2 cases. In training series the model correctly classifies 79 out of 80 (specificity = 98.75%) set1 and 226 out of 238 (Sensitivity = 94.96%) set2 trajectories. In independent validation series the model correctly classifies 26 out of 26 (specificity = 100%) set1 and 75 out of 78 (sensitivity = 96.15%) set2 trajectories. We propose this new model as a scoring function to guide DNA-docking studies in the drug design of new coumarins for anticancer or antiparasitic PUVA therapy.

DNA cleavage in red light promoted by copper(ii) complexes of α-amino acids and photoactive phenanthroline bases

Ternary copper(II) complexes [Cu(L-trp)(B)(H(2)O)](NO(3)) (1-3) and [Cu(L-phe)(B)(H(2)O)](NO(3)) (4-6) of L-tryptophan (L-trp) and L-phenylalanine (L-phe) having phenanthroline bases (B), viz. 1,10-phenanthroline (phen, 1 and 4), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2 and 5) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3 and 6), were prepared and characterized by physico-chemical techniques. Complexes 3 and 6 were structurally characterized by X-ray crystallography and show the presence of a square pyramidal (4 + 1) CuN(3)O(2) coordination geometry in which the N,O-donor amino acid (L-trp or L-phe) and N,N-donor phenanthroline base bind at the equatorial plane with an aqua ligand coordinated at the elongated axial site. Complex 3 shows significant distortion from the square pyramidal geometry and a strong intramolecular pi-pi stacking interaction between the pendant indole ring of L-trp and the planar dppz aromatic moiety. All the complexes display good binding propensity to the calf thymus DNA giving an order: 3,6 (dppz) > 2,5 (dpq) > 1,4 (phen). The binding constant (K(b)) values are in the range of 2.1 x 10(4)-1.1 x 10(6) mol(-1) with the binding site size (s) values of 0.17-0.63. The phen and dpq complexes are minor groove binders while the dppz analogues bind at the DNA major groove. Theoretical DNA docking studies on 2 and 3 show the close proximity of two photosensitizers, viz. the indole moiety of L-trp and the quinoxaline/phenazine of the dpq/dppz bases, to the complementary DNA strands. Complexes 2 and 3 show oxidative DNA double strand breaks (dsb) of supercoiled (SC) DNA forming a significant quantity of linear DNA along with the nicked circular (NC) form on photoexposure to UV-A light of 365 nm and red light of 647.1 nm (Ar-Kr laser). Complexes 1,5 and 6 show only single strand breaks (ssb) forming NC DNA. The red light induced DNA cleavage involves metal-assisted photosensitization of L-trp and dpq/dppz base resulting in the formation of a reactive singlet oxygen ((1)O(2)) species.

Binding geometry of cobalt bleomycin, an empirical force-field analysis

Empirical force-field calculations have shown that the co-ordination geometry 1 of bleomycin (BLM) binding to cobalt proposed by Umezawa and that, 2, proposed by Hilbers is sterically possible. In the calculations it was found that changing the charge on the metal ion has a significant effect on the BLM conformation, however the differences in conformation between the two binding geometries are much larger than those due to charge differences. Based on BLM–DNA docking studies, it is suggested that both the bithiazole tail and the metal-binding region of BLM with binding geometry 2 could be interacting with the minor groove of DNA.