Emergent multipath COVID-19 specimen collection problem with green corridor through variable length GA.

The COVID-19 pandemic has spread worldwide exponentially. Typically, for testing, a provincial main government hospital cum testing center collects patients' specimens from remote health centers in the minimum possible time, satisfying the 'false negativity' constraint of the first collected specimen. With infrastructural developments throughout the world, multiple paths are available for transportation between two cities. Currently, the 'green corridor' is used for the transportation of human organs to be implanted, travel of VIPs, etc., in the minimum possible time. Taking these facts in consideration, for the first time, a green corridor system is suggested to provide a transportation pathway from small hospitals and urban/rural health centers to the testing center with COVID-19 specimens such as blood, nasal and throat swabs, and viral RNA, within the first collected specimen's life period. As health centers are located in different places, appropriate routing plans are needed for visiting them in the minimum possible time. A problem arises if this routing time exceeds the 'false negativity' of the first collected specimen. Thus, multipath COVID-19 specimen collection problems (MPC-19SCPs) are mathematically formulated to be collected from all health centers, and optimum routing plans are obtained using fixed and variable length genetic algorithms (VLGAs) developed for this purpose. For the first time, green corridor systems are suggested to incorporate the centers. The objectives of the models are, subject to the 'false-negative" constraint, minimization of the system time (Model A) and the green corridor time without or with mutual cooperation among the minimum number of centers for the transfer of specimens (Models B and C, respectively). The developed algorithms are based on variable length chromosomes, probabilistic selection, comparison crossover and generation-dependent mutation. Some benchmark instances from TSPLIB are solved by VLGA and GA. The competitiveness of VLGA is established through ANOVA. The models are numerically demonstrated, and some conclusions are derived.

Engineering Hydrogels for the Development of Three-Dimensional In Vitro Models.

The superiority of in vitro 3D cultures over conventional 2D cell cultures is well recognized by the scientific community for its relevance in mimicking the native tissue architecture and functionality. The recent paradigm shift in the field of tissue engineering toward the development of 3D in vitro models can be realized with its myriad of applications, including drug screening, developing alternative diagnostics, and regenerative medicine. Hydrogels are considered the most suitable biomaterial for developing an in vitro model owing to their similarity in features to the extracellular microenvironment of native tissue. In this review article, recent progress in the use of hydrogel-based biomaterial for the development of 3D in vitro biomimetic tissue models is highlighted. Discussions of hydrogel sources and the latest hybrid system with different combinations of biopolymers are also presented. The hydrogel crosslinking mechanism and design consideration are summarized, followed by different types of available hydrogel module systems along with recent microfabrication technologies. We also present the latest developments in engineering hydrogel-based 3D in vitro models targeting specific tissues. Finally, we discuss the challenges surrounding current in vitro platforms and 3D models in the light of future perspectives for an improved biomimetic in vitro organ system.

Synthesis, Characterization, and Water Oxidation Activity of Isomeric Ru Complexes.

The synthesis and characterization of the isomeric ruthenium complexes with the general formula cis- and trans-[Ru(trpy)(qc)X]n+ (trpy is 2,2':6',2″-terpyridine, qc is 8-quinolinecarboxylate, cis-1 and trans-1, X = Cl, n = 0; cis-2 and trans-2, X=OH2, n = 1) with respect to the relative disposition of the carboxylate and X ligands are reported. For comparison purposes, another set of ruthenium complexes with general formula cis- and trans-[Ru(trpy)(pic)(OH2)]+ (pic is 2-picolinate (cis-3, trans-3)) have been prepared. The complexes with a qc ligand show a more distorted geometry compared to the complexes with a pic ligand. In all of the cases, the trans isomers show lower potential values for all of the redox couples relative to the cis isomers. Complexes cis-2 and trans-2 with six-member chelate rings show higher catalytic activity than cis-3 and trans-3. Overall, it was shown that the electronic perturbation to the metal center exerted by different orientation and geometry of the ligands significantly influences both redox properties and catalytic performance.

Fractal self-assembly and aggregation of human amylin.

Human amylin is an intrinsically disordered protein believed to have a central role in Type-II diabetes mellitus (T2DM). The formation of intermediate oligomers is a seminal event in the eventual self-assembled fibril structures of amylin. However, the recent experimental investigations have shown the presence of different self-assembled (oligomers, protofilaments, and fibrils) and aggregated structures (amorphous aggregates) of amylin formed during its aggregation. Here, we show that amylin under diffusion-limited conditions leads to fractal self-assembly. The pH and solvent sensitive fractal self-assemblies of amylin were observed using an optical microscope. Confocal microscopy and scanning electron microscopy (SEM) with energy dispersion X-ray analysis (EDAX) were used to confirm the fractal self-assembly of amylin in water and PBS buffer, respectively. The fractal characteristics of the self-assemblies and the aggregates formed during the aggregation of amylin under different pH conditions were investigated using laser light scattering. The hydropathy and the docking study indicated the interactions between the anisotropically distributed hydrophobic residues and polar/ionic residues on the solvent-accessible surface of the protein as the crucial interaction hot-spots for driving the self-assembly and aggregation of human amylin. The simultaneous presence of various self-assemblies of human amylin was observed through different microscopy techniques. The present study may help in designing different fractal-like nanomaterials with potential applications in drug delivery, sensing, and tissue engineering.

A water soluble light activated hydrogen sulfide donor induced by an excited state meta effect.

We have utilized an m-amino benzyl based photoremovable protecting group (PRPG) to develop a new water soluble H2S donor. It efficiently releases H2S on demand in a spatio-temporally controlled fashion by an excited state "meta effect" with good chemical and photochemical quantum yield in an aqueous environment. The efficient photorelease of H2S under physiological conditions was also demonstrated by in vitro studies.

Molecular Mechanisms Associated With Particulate and Soluble Heteroglycan Mediated Immune Response.

Immune responses are outcomes of complex molecular machinery which occur inside the cells. Unravelling the cellular mechanisms induced by immune stimulating molecules such as glycans and determining their structure-function relationship are therefore important factors to be assessed. With this viewpoint, the present study identifies the functional receptor binding unit of a well characterized heteroglycan and also delineates the cellular and molecular processes that are induced upon heteroglycan binding to specific cell surface receptors in immune cells. The heteroglycan was acid hydrolysed and it was revealed that 10-30 kDa fractions served as the functional receptor binding unit of the molecule. Increasing the size of 10-30 kDa heteroglycan showed prominent immune activity. The whole soluble heteroglycan was also conjugated with hyperbranched dendrimers so as to generate a particulate form of the molecule. Dectin-1 and TLR2 were identified as the major receptors in macrophages that bind to particulate as well as soluble form of the heteroglycan and subsequently caused downstream signaling molecules such as NF-κß and MAPK to get activated. High levels of 1L-1ß and IL-10 mRNA were observed in particulate heteroglycan treated macrophages, signifying that increasing the size and availability of the heteroglycan to its specific receptors is pertinent to its biological functioning. Upregulated expression of PKC and iNOS were also noted in particulate heteroglycan treated RAW 264.7 cells than the soluble forms. Taken together, our results indicate that biological functions of immunomodulatory heteroglycan are dependent on their size and molecular weight. J. Cell. Biochem. 117: 1580-1593, 2016. © 2015 Wiley Periodicals, Inc.

Direct Evidence of a Tryptophan Analogue Radical Formed in a Concerted Electron-Proton Transfer Reaction in Water.

Proton-coupled electron transfer (PCET) is a fundamental reaction step of many chemical and biological processes. Well-defined biomimetic systems are promising tools for investigating the PCET mechanisms relevant to natural proteins. Of particular interest is the possibility to distinguish between stepwise and concerted transfer of the electron and proton, and how PCET is controlled by a proton acceptor such as water. Thus, many tyrosine and phenolic derivatives have been shown to undergo either stepwise or concerted PCET, where the latter process is defined by simultaneous tunneling of the electron and proton from the same transition state. For tryptophan instead, it is theoretically predicted that a concerted pathway can never compete with the stepwise electron-first mechanism (ETPT) when neat water is the primary proton acceptor. The argument is based on the radical pK(a) (∼4.5) that is much higher than that for water (pK(a)(H3O(+)) = 0), which thermodynamically disfavors a concerted proton transfer to H2O. This is in contrast to the very acidic radical cation of tyrosine (pK(a) ∼ -2). However, in this study we show, by direct time-resolved absorption spectroscopy on two [Ru(bpy)3](2+)-tryptophan (bpy = 2,2'-bipyridine) analogue complexes, that also tryptophan oxidation with water as a proton acceptor can occur via a concerted pathway, provided that the oxidant has weak enough driving force. This rivals the theoretical predictions and suggests that our current understanding of PCET reactions in water is incomplete.

Judicious Ligand Design in Ruthenium Polypyridyl CO2 Reduction Catalysts to Enhance Reactivity by Steric and Electronic Effects.

A series of RuII polypyridyl complexes of the structural design [RuII (R-tpy)(NN)(CH3 CN)]2+ (R-tpy=2,2':6',2''-terpyridine (R=H) or 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine (R=tBu); NN=2,2'-bipyridine with methyl substituents in various positions) have been synthesized and analyzed for their ability to function as electrocatalysts for the reduction of CO2 to CO. Detailed electrochemical analyses establish how substitutions at different ring positions of the bipyridine and terpyridine ligands can have profound electronic and, even more importantly, steric effects that determine the complexes' reactivities. Whereas electron-donating groups para to the heteroatoms exhibit the expected electronic effect, with an increase in turnover frequencies at increased overpotential, the introduction of a methyl group at the ortho position of NN imposes drastic steric effects. Two complexes, [RuII (tpy)(6-mbpy)(CH3 CN)]2+ (trans-[3]2+ ; 6-mbpy=6-methyl-2,2'-bipyridine) and [RuII (tBu-tpy)(6-mbpy)(CH3 CN)]2+ (trans-[4]2+ ), in which the methyl group of the 6-mbpy ligand is trans to the CH3 CN ligand, show electrocatalytic CO2 reduction at a previously unreactive oxidation state of the complex. This low overpotential pathway follows an ECE mechanism (electron transfer-chemical reaction-electron transfer), and is a direct result of steric interactions that facilitate CH3 CN ligand dissociation, CO2 coordination, and ultimately catalytic turnover at the first reduction potential of the complexes. All experimental observations are rigorously corroborated by DFT calculations.

Establishing the Family of Diruthenium Water Oxidation Catalysts Based on the Bis(bipyridyl)pyrazolate Ligand System.

A bis(bipyridyl)pyrazolate ((Me)bbp(-)) has recently been introduced as a rugged dinucleating, bis(tridentate) ligand for the formation of efficient diruthenium water oxidation catalysts (J. Am. Chem. Soc. 2014, 136, 24-27). Now, detailed protocols for the synthesis of a whole family of such dinuclear ruthenium complexes [{Ru(pyR(2))2}2(µ-(R1)bbp)(X,Y)](2+) based on the bis(bipyridyl)pyrazolate scaffold are reported. The isolation of a synthetic key intermediate allowed the straightforward introduction of different pyridines as axial ligands. Thereby, a set of complexes with different substituents at the pyrazolate backbone (R(1) = Br, H, Me), different pyridines as axial ligand (R(2) = H, NMe2, SO3), and different (non)bridging units in the in,in-position (X,Y = Cl, H2O, OAc) has been prepared and thoroughly characterized. Complexes of the type [{Ru(pyR(2))2}2(µ-(R1)bbp)(µ-OAc)](2+), with an exogenous acetato bridge, have been used as catalyst precursors in catalytic water oxidation experiments with a sacrificial oxidant. The effect of substitution on the pyrazole core of the (R1)bbp(-) ligand as well as on the pyridine ligands on both electrochemistry and catalytic activity has been systematically investigated. The catalyst stability, reflected by the turnover number, is crucially determined by the substituent at the pyrazolate ligand (R(1) = Me > H > Br). In contrast, the axial pyridine ligands modulate the rate of the catalytic process, expressed by the initial turnover frequency (R(2) = H > NMe2H(+)).

Activating a Low Overpotential CO2 Reduction Mechanism by a Strategic Ligand Modification on a Ruthenium Polypyridyl Catalyst.

The introduction of a simple methyl substituent on the bipyridine ligand of [Ru(tBu3 tpy)(bpy)(NCCH3 )](2+) (tBu3 tpy=4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine; bpy=2,2'-bipyridine) gives rise to a highly active electrocatalyst for the reduction of CO2 to CO. The methyl group enables CO2 binding already at the one-electron reduced state of the complex to enter a previously not accessible catalytic cycle that operates at the potential of the first reduction. The complex turns over with a Faradaic efficiency close to unity and at an overpotential that is amongst the lowest ever reported for homogenous CO2 reduction catalysts.

Molecular water oxidation mechanisms followed by transition metals: state of the art.

One clean alternative to fossil fuels would be to split water using sunlight. However, to achieve this goal, researchers still need to fully understand and control several key chemical reactions. One of them is the catalytic oxidation of water to molecular oxygen, which also occurs at the oxygen evolving center of photosystem II in green plants and algae. Despite its importance for biology and renewable energy, the mechanism of this reaction is not fully understood. Transition metal water oxidation catalysts in homogeneous media offer a superb platform for researchers to investigate and extract the crucial information to describe the different steps involved in this complex reaction accurately. The mechanistic information extracted at a molecular level allows researchers to understand both the factors that govern this reaction and the ones that derail the system to cause decomposition. As a result, rugged and efficient water oxidation catalysts with potential technological applications can be developed. In this Account, we discuss the current mechanistic understanding of the water oxidation reaction catalyzed by transition metals in the homogeneous phase, based on work developed in our laboratories and complemented by research from other groups. Rather than reviewing all of the catalysts described to date, we focus systematically on the several key elements and their rationale from molecules studied in homogeneous media. We organize these catalysts based on how the crucial oxygen-oxygen bond step takes place, whether via a water nucleophilic attack or via the interaction of two M-O units, rather than based on the nuclearity of the water oxidation catalysts. Furthermore we have used DFT methodology to characterize key intermediates and transition states. The combination of both theory and experiments has allowed us to get a complete view of the water oxidation cycle for the different catalysts studied. Finally, we also describe the various deactivation pathways for these catalysts.

Oxo-bridge scenario behind single-site water-oxidation catalysts.

High-oxidation-state decay of mononuclear complexes [RuTB(H2O)](2+) (X(2+), where B = 2,2'-bpy or bpy for X = 1; B = 5,5'-F2-bpy for X = 2; B = 6,6'-F2-bpy for X = 3; T = 2,2':6',2″-terpyridine) oxidized with a large excess of Ce(IV) generates a manifold of polynuclear oxo-bridged complexes. These include the following complexes: (a) dinuclear [TB-Ru(IV)-O-Ru(IV)-(T)(O)OH2](2+) (1-dn(4+)), [TB-Ru(III)-O-Ru(III)-T(MeCN)2](4+) (1-dn-N(4+)), and {[Ru(III)(trpy)(bpy)]2(µ-O)}(4+) (1-dm(4+)); (b) trinuclear {[Ru(III)(trpy)(bpy)(µ-O)]2Ru(IV)(trpy)(H2O)}(ClO4)5(6+) (1-tr(6+)) and {[Ru(III)(trpy)(bpy)(µ-O)]2Ru(IV)(pic)2}(ClO4)4 (1-tr-P(4+), where P is the 2-pyridinecarboxylate anion); and (c) tetranuclear [TB-Ru(III)-O-TRu(IV)(H2O)-O-TRu(IV)(H2O)-O-Ru(III)-TB](8+) (1-tn(8+)), [TB-Ru(III)-O-TRu(IV)(AcO)-O-TRu(IV)(AcO)-O-Ru(III)-TB](6+) (1-tn-Ac(6+)), and [TB-Ru(II)-O-TRu(IV)(MeCN)-O-TRu(IV)(MeCN)-O-Ru(II)-TB](6+) (1-tn-N(6+)). These complexes have been characterized structurally by single-crystal X-ray diffraction analysis, and their structural properties were correlated with their electronic structures. Dinuclear complex 1-dm(4+) has been further characterized by spectroscopic and electrochemical techniques. Addition of excess Ce(IV) to 1-dm(4+) generates dioxygen in a catalytic manner. However, resonance Raman spectroscopy points to the in situ formation of 1-dn(4+) as the active species.

Tunable Electrochemical and Catalytic Features of BIAN- and BIAO-Derived Ruthenium Complexes.

This article deals with a class of ruthenium-BIAN-derived complexes, [Ru(II)(tpm)(R-BIAN)Cl]ClO4 (tpm = tris(1-pyrazolyl)methane, R-BIAN = bis(arylimino)acenaphthene, R = 4-OMe ([1a]ClO4), 4-F ([1b]ClO4), 4-Cl ([1c]ClO4), 4-NO2 ([1d]ClO4)) and [Ru(II)(tpm)(OMe-BIAN)H2O](2+) ([3a](ClO4)2). The R-BIAN framework with R = H, however, leads to the selective formation of partially hydrolyzed BIAO ([N-(phenyl)imino]acenapthenone)-derived complex [Ru(II)(tpm)(BIAO)Cl]ClO4 ([2]ClO4). The redox-sensitive bond parameters involving -N═C-C═N- or -N═C-C═O of BIAN or BIAO in the crystals of representative [1a]ClO4, [3a](PF6)2, or [2]ClO4 establish its unreduced form. The chloro derivatives 1a(+)-1d(+) and 2(+) exhibit one oxidation and successive reduction processes in CH3CN within the potential limit of ±2.0 V versus SCE, and the redox potentials follow the order 1a(+) < 1b(+) < 1c(+) < 1d(+) ≈ 2(+). The electronic structural aspects of 1a(n)-1d(n) and 2(n) (n = +2, +1, 0, -1, -2, -3) have been assessed by UV-vis and EPR spectroelectrochemistry, DFT-calculated MO compositions, and Mulliken spin density distributions in paramagnetic intermediate states which reveal metal-based (Ru(II) → Ru(III)) oxidation and primarily BIAN- or BIAO-based successive reduction processes. The aqua complex 3a(2+) undergoes two proton-coupled redox processes at 0.56 and 0.85 V versus SCE in phosphate buffer (pH 7) corresponding to {Ru(II)-H2O}/{Ru(III)-OH} and {Ru(III)-OH}/{Ru(IV)═O}, respectively. The chloro (1a(+)-1d(+)) and aqua (3a(2+)) derivatives are found to be equally active in functioning as efficient precatalysts toward the epoxidation of a wide variety of alkenes in the presence of PhI(OAc)2 as oxidant in CH2Cl2 at 298 K, though the analogous 2(+) remains virtually inactive. The detailed experimental analysis with the representative precatalyst 1a(+) suggests the involvement of the active {Ru(IV)═O} species in the catalytic cycle, and the reaction proceeds through the radical mechanism, as also supported by the DFT calculations.

New powerful and oxidatively rugged dinuclear Ru water oxidation catalyst: control of mechanistic pathways by tailored ligand design.

A new powerful and oxidatively rugged pyrazolate-based water oxidation catalyst of formula {[Ru(II)(py-SO3)2(H2O)]2(µ-Mebbp)}(-), 1(H2O)2(-), has been prepared and thoroughly characterized spectroscopically and electrochemically. This new catalyst has been conceived based on a specific ligand tailoring design, so that its performance has been systematically improved. It was also demonstrated how subtle ligand modifications cause a change in the O-O bond formation mechanism, thus revealing the close activation energy barriers associated with each pathway.

Direct observation of key catalytic intermediates in a photoinduced proton reduction cycle with a diiron carbonyl complex.

The structure and reactivity of intermediates in the photocatalytic cycle of a proton reduction catalyst, [Fe2(bdt)(CO)6] (bdt = benzenedithiolate), were investigated by time-resolved spectroscopy. The singly reduced catalyst [Fe2(bdt)(CO)6](-), a key intermediate in photocatalytic H2 formation, was generated by reaction with one-electron reductants in laser flash-quench experiments and could be observed spectroscopically on the nanoseconds to microseconds time scale. From UV/vis and IR spectroscopy, [Fe2(bdt)(CO)6](-) is readily distinguished from the two-electron reduced catalyst [Fe2(bdt)(CO)6](2-) that is obtained inevitably in the electrochemical reduction of [Fe2(bdt)(CO)6]. For the disproportionation rate constant of [Fe2(bdt)(CO)6](-), an upper limit on the order of 10(7) M(-1) s(-1) was estimated, which precludes a major role of [Fe2(bdt)(CO)6](2-) in photoinduced proton reduction cycles. Structurally [Fe2(bdt)(CO)6](-) is characterized by a rather asymmetrically distorted geometry with one broken Fe-S bond and six terminal CO ligands. Acids with pK(a) ≤ 12.7 protonate [Fe2(bdt)(CO)6](-) with bimolecular rate constants of 4 × 10(6), 7 × 10(6), and 2 × 10(8) M(-1) s(-1) (trichloroacetic, trifluoroacetic, and toluenesulfonic acids, respectively). The resulting hydride complex [Fe2(bdt)(CO)6H] is therefore likely to be an intermediate in photocatalytic cycles. This intermediate resembles structurally and electronically the parent complex [Fe2(bdt)(CO)6], with very similar carbonyl stretching frequencies.

A self-improved water-oxidation catalyst: is one site really enough?

The homogeneous catalysis of water oxidation by transition-metal complexes has experienced spectacular development over the last five years. Practical energy-conversion schemes, however, require robust catalysts with large turnover frequencies. Herein we introduce a new oxidatively rugged and powerful dinuclear water-oxidation catalyst that is generated by self-assembly from a mononuclear catalyst during the catalytic process. Our kinetic and DFT computational analysis shows that two interconnected catalytic cycles coexist while the mononuclear system is slowly and irreversibly converted into the more stable dinuclear system: an extremely robust water-oxidation catalyst that does not decompose over extended periods of time.

Mononuclear copper(II) complexes with polypyridyl ligands: synthesis, characterization, DNA interactions/cleavages and in vitro cytotoxicity towards human cancer cells.

DNA being the necessary element in cell regeneration, controlled cellular apoptosis via DNA binding/cleaving is considered an approach to combat cancer cells. The widely prescribed metallodrug cisplatin has shown interactions with the guanine-N7 center, and a plethora of complexes are continually developed to enhance crosslinking properties as well as covalent and non-covalent interactions. Two pentadentate ligands, L1 (1-(6-(1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) and L2 (1-(6-(1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine), were synthesized together with their respective copper(II) complexes [1](ClO4)2 and [2](ClO4)2, which crystallized in a trigonal bipyramidal fashion. Different analytical and spectroscopic methods confirmed their formation, and their redox behaviour was also examined. The interactions of salmon sperm DNA (ss-DNA) with these two complexes were explored using absorbance spectroscopy, and they both exhibited a binding affinity (Kb) of ∼104 M-1. Fluorescence quenching experiments with ethidium bromide (EB)-bound DNA (EB-DNA) were also performed, and Stern-Volmer constant (KSV) values of 6.93 × 103 and 2.34 × 104 M-1 for [1](ClO4)2 and [2](ClO4)2, respectively, were obtained. Furthermore, DNA conformational changes due to the interactions of both complexes were validated via circular dichroism. We also assessed the DNA cleavage property of these complexes, which resulted in the linearization of circular plasmid DNA. This finding was supported by studying the growth of MDA-MB-231 breast cancer cells upon treatment with both Cu(II) complexes; IC50 values of 5.34 ± 1.02 µM and 0.83 ± 0.18 µM were obtained for [1](ClO4)2 and [2](ClO4)2, respectively. This validates their affinity towards DNA, and these insights can be further utilized for non-platinum based economical metallodrug development based on first row transition metals.

Chromophore appended DPA-based copper(II) complexes with a diimine motif towards DNA binding and fragmentation studies.

Mixed ligand copper(II) complexes [Cu(L1)(bpy)](ClO4)21 and [Cu(L2)(bpy)](ClO4)22 (where L1 = 1-(anthracen-9-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine, L2 = 1-(pyren-1-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine and bpy = 2,2'-bipyridine) were synthesised and characterised thoroughly via different analytical and spectroscopic techniques i.e., UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, HRMS and EPR spectroscopy. The molecular structures of the synthesised complexes were obtained using the single-crystal X-ray diffraction technique. Both complexes exhibited penta-coordinated and acquired distorted square pyramidal geometry. The redox behaviour of complexes 1 and 2 was investigated by employing cyclic voltammetry. The DNA binding study was carried out by UV-vis spectrophotometry using double-stranded salmon sperm DNA (ds-ss-DNA). The binding constant (Kb) values of 1 and 2 were 0.11 × 104 M-1 and 1.05 × 104 M-1, respectively, which indicates that 2 has better binding ability than 1. This might be due to the higher conjugative abilities with the extended surface area of the aromatic pyrene ring compared to the anthracene moiety. The fluorescence quenching experiments were also performed with EB bound DNA (EB-DNA) and Stern-Volmer constant (KSV) values were calculated as 1.23 × 105 M-1 and 1.39 × 105 M-1 for 1 and 2, respectively, suggesting that 2 showed stronger interaction with ss-DNA than 1. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA varying with 1 and 2. Evaluation of the DNA binding properties of the complexes to linearized plasmid DNA indicated that 2 had modest DNA binding properties, which is a pre-requisite for a genotoxic agent. The effect of 1 and 2 on cell survival was analysed using HeLa cells by MTT assay and it was observed that the IC50 values of 1 and 2 were 43.7 µM and 18.6 µM, respectively. Our study paves the way for the designing of bio-inspired novel mixed metal complexes, which shows promising results for further exploration of molecular and mechanistic studies towards the development of non-platinum based economical metallodrugs.

Synthesis, characterization, and reactivity of dyad ruthenium-based molecules for light-driven oxidation catalysis.

Dyad molecules containing the 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tppz) ligand with general formula [(tpy)Ru(µ-tppz)Ru(X)(L-L)](n+) (X=Cl, CF3COO, or H2O; L-L=2,2'-bipyridine (bpy) or 3,5-bis(2-pyridyl)pyrazole (Hbpp); tpy=2,2':6',2"-terpyridine) have been prepared, purified, and isolated. The complexes have been characterized by analytical and spectroscopic techniques and by X-ray diffraction analysis for two of them. Additionally, full electrochemical characterization based on cyclic voltammetry, differential pulse voltammetry, and square wave voltammetry has been also performed. The pH dependence of the redox couples for the aqua complexes have also been studied and their corresponding Pourbaix diagrams drawn. Furthermore, their capacity to catalytically oxidize organic substrates, such as alcohols, alkenes, and sulfides, has been carried out chemically, electrochemically, and photochemically. Finally, their capacity to behave as water oxidation catalysts has also been tested.