Browsing by Author "Bellam, Rajesh"

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    PublicationOpen Access
    Heterodinuclear Ru–Pt Complexes Bridged with 2,3-Bis(pyridyl)pyrazinyl Ligands: Studies on Kinetics, Deoxyribonucleic Acid/Bovine Serum Albumin Binding and Cleavage, In Vitro Cytotoxicity, and In Vivo Toxicity on Zebrafish Embryo Activities
    (ACS Omega, 2022-07-21) Bellam, Rajesh; Jaganyi, Deogratius.; Robinson, Ross Stuart.
    Di- and poly-homo/heteronuclear complexes have great potential as anticancer drugs. Here, we report their reactivity, deoxyribonucleic acid (DNA)/bovine serum albumin (BSA) binding and cleavage interactions, in vitro cytotoxicity, and in vivo zebrafish embryo toxicity of [(phen)2Ru(μ-L)PtCl2]2+ (phen = 1,10-phenanthroline and L = 2,3-bis(2-pyridyl)pyrazine, bpp, C1; 2,3-bis(2-pyridyl)quinoxaline, bpq, C2ial; 2,3-bis(2-pyridyl)benzo[g]quinoxaline, bbq, C3) anticancer prodrugs. The substitution reactivity increases from C1 to C3 owing to an increase in the π-conjugation on the bridging chelate which facilitates π-back bonding. As a result, the electrophilicity index on the C3 complex increases than that on the complex C2 followed by C1 which leads to higher rates of substitution and thus the reactivity order follows C1 < C2 < C3. The coordination of Ru at one end of each of the complexes enhances water solubility. Moreover, the charge addition of the two metal ions increases their reactivity toward substitution in addition to ensuring electrostatic interactions at target sites such as the DNA/BSA. Spectroscopic (UV–vis absorption and fluorescence quenching) titration and viscosity measurement results of the interactions of C1/2/3 with CT-DNA established the formation of stable, nonconvent C1/2/3-DNA adducts with DNA most likely via the intercalative binding mode. Furthermore, studies with BSA showed a good binding affinity of these complexes owing to hydrophobic interactions with the coordinated ligands. The interactions of these complexes with DNA/BSA are in line with the reactivity trend, and all these experimental findings were further supported by molecular docking analysis. In vitro MTT cytotoxic activities on human breast cancer cell line MCF-7 revealed that all the complexes have high cytotoxicity activity (IC50 > 9 μM); furthermore, the selectivity index and SI values were higher (>3). Complex C3 showed the highest cytotoxicity with IC50 = 3.1 μM and SI value (5.55) against MCF7 cell lines and these values were comparable to those of the cisplatin (IC50 and SI values are 5.0 μM and 4.02, respectively). In vivo toxicological assessments on zebrafish embryos revealed that all the Ru–Pt complexes (CI/2/3) have poor embryo acute toxic effects over 96 h postfertilization, hpf with LC50 > 65.2 μM. The complex C3 has shown the lowest embryo toxicity (LC50 = 148.8 μM), which is comparable to that of commercial cisplatin (LC50 = 181.1 μM). Based on the cytotoxicity results, complexes C2 and C3 could be considered for further development as chemotherapeutic agents against MCF breast cancer cells.
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    Kinetics and mechanism of base hydrolysis of tris(3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine)iron(II) in aqueous and micellar media
    (Springer link, 2015-12-26) Jaganyi, Deo; Bellam, Rajesh; Raju, G. Ganga; Anipindi, Nageswara Rao
    The kinetics of base hydrolysis of tris(3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine)iron(II), has been studied in aqueous, cetyltrimethyl ammonium bromide (CTAB) and sodium dodecyl sulphate (SDS) media at 25, 35 and 45 °C under pseudo-first-order conditions, i.e. . The reactions are first order in both of substrate and hydroxide ion. The rates decrease with increasing ionic strength in aqueous and CTAB media, whereas SDS medium shows little ionic strength effect. The rate also increases with CTAB concentration but decreases with SDS. The specific rate constant, k and thermodynamic parameters (E a, ΔH #, ΔS # and ΔG #) have also been evaluated. The near equal values of ΔG # obtained in aqueous and CTAB media suggest that these reactions occur essentially by the same mechanism such that reacts with OH− in the rate-determining step. The ionic strength effect in SDS medium suggests that the rate-determining step involves an ion and a neutral species. The results in this study are compared with those obtained for other iron(II)-bipyridine complexes.
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    PublicationOpen Access
    Seven membered chelate Pt(ii) complexes with 2,3-di(2-pyridyl)quinoxaline ligands: studies of substitution kinetics by sulfur donor nucleophiles, interactions with CT-DNA, BSA and in vitro cytotoxicity activities
    (Royal society of chemistry, 2019-10-07) Bellam, Rajesh; Mambanda,Allen; Robinson, Ross; Dakshinamoorthi BalaKumaran, Manickam
    Dichloro platinum(II) complexes coordinated with 2,3-di(2-pyridyl)quinoxaline ligands which form seven-membered chelates namely, bpqPtCl2, dmbpqPtCl2 and bbqPtCl2 (where bpq, dmbpq and bbq are 2,3-di(2-pyridyl)quinoxaline, 6,7-dimethyl-2,3-di(2-pyridyl)quinoxaline and 2,3-bis(2′pyriyl)benzo[g]quinoxaline, respectively) were synthesized, characterised and their respective hydrated product complexes namely, bpqPt(OH2)22+, dmbpqPt(OH2)22+ and bbqPt(OH2)22+ were prepared by chloride metathesis. The substitution kinetics of the aquated cations by thiourea nucleophiles indicated that the two aqua ligands are substituted simultaneously according to the rate law: kobs = k2[Nu]. This is followed by a forced dechelation of the ligands from the Pt (II) to form Pt(Nu)42+ species. The dechelation step is considerably slow to be monitored reliably. The rate of substitution is marginally enhanced by introducing two methyl groups and by extending the π-conjugation on the bpq core ligand. The reactivity order increased as bpqPt(OH2)22+ < dmbpqPt(OH2)22+ < bbqPt(OH2)22+. Reactivity trends were well supported by theoretical computed DFT electronic descriptors. The interactions of the Pt(II) complexes with CT-DNA and BSA were also examined spectroscopically in tris buffers at pH 7.2. Spectroscopic and viscosity measurements suggested strong associative interactions between the Pt(II) complexes and CT-DNA, most likely through groove binding. In silico theoretical binding studies showed energetically stable poses through associative non-covalent interactions. In vitro MTT cytotoxicity IC50 values of the Pt(II) complexes on human liver carcinoma cells (HepG2) cancer cell lines revealed bbqPtCl2 as the least active. The fluorescence staining assays revealed the morphological changes suggested early apoptotic induction as well as non-specific necrosis.
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    Substitution Kinetics of [Fe(PDT/PPDT)n(phen)m]2+ (n ≠ m; n,m = 1,2) with 2,2′-Bipyridine, 1,10-Phenanthroline, and 2,2′,6,2″-Terpyridine
    (International Journal of Chemical Kinetics, 2017-01-23) Jaganyi, Deogratius; Bellam, Rajesh
    The triazines 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (PDT), 3-(4-phenyl-2-pyridyl)-5,6-diphenyl-1,2,4-triazine (PPDT), and 1,10-phenanthroline (phen) were coordinated to the Fe2+ ion to form urn:x-wiley:05388066:media:kin21066:kin21066-math-0001 (1), urn:x-wiley:05388066:media:kin21066:kin21066-math-0002 (2), urn:x-wiley:05388066:media:kin21066:kin21066-math-0003, (3) and urn:x-wiley:05388066:media:kin21066:kin21066-math-0004 (4). The complexes were synthesized and characterized by mass spectroscopy and elemental analysis. The rate of substitution of these complexes by 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), and 2,2′,6,2″-terpyridine (terpy) was studied in a sodium acetate–acetic acid buffers over the range 3.6–5.6 at 25, 35, and 45°C under pseudo–first-order conditions. The reactions are first order with respect to the concentration of the complexes. The reaction rates increase with increasing [bpy/phen/terpy] and pH, whereas ionic strength has no influence on the rate of reaction. Plots of kobs versus [bpy/phen/terpy] and 1/[H+] are linear with positive slopes and significant y-intercepts. This indicates that the reactions proceed by both dissociative as well as associative pathways for which the associative pathway predominates the substitution kinetics. Observed temperature-depended rate constants at the three temperatures at which substitution reactions were studied together with the protonation constants of the substituting ligands (phen, bpy, terpy) were used to evaluate the specific rate constants (k1 and k2) and thermodynamic parameters (Ea, ΔH#, ΔS#, and ΔG#). The reactivity order of the four complexes depends on the phenyl groups present on the triazine (PDT/PPDT) molecule. The π-electrons on phenyl rings stabilizes the charge on the metal center by inductive donation of electrons toward the metal center resulting in a decrease in reactivity of the complex, and the order is 1 < 2 < 3 < 4. The rate of substitution is also influenced by the basicity of the incoming ligand (bpy/phen/terpy), and it decreased in the order: phen > terpy > bpy. Higher rate constants, low Ea values, and more negative entropy of activation (−ΔS#) values were observed for the associative path, revealing that substitution reactions at the octahedral iron(II) complexes by bpy, phen, and terpy occur predominantly by the associative mechanism. Density functional theory calculations support the interpretations.