Towards Understanding the Structure, Dynamics and Bio-activity of Diabetic Drug Metformin

Small molecules are often found to exhibit extraordinarily diverse biological activities. Metformin is one of them. It is widely used as anti-diabetic drug for type-two diabetes. In addition to that, metformin hydrochloride shows anti-tumour activities and increases the survival rate of patients suffering from certain types of cancer namely colorectal, breast, pancreas and prostate cancer. However, theoretical studies of structure and dynamics of metformin have not yet been fully explored. In this work, we investigate the characteristic structural and dynamical features of three mono-protonated forms of metformin hydrochloride with the help of experiments, quantum chemical calculations and atomistic molecular dynamics simulations. We validate our force field by comparing simulation results to that of the experimental findings. Nevertheless, we discover that the non-planar tautomeric form is the most stable. Metformin forms strong hydrogen bonds with surrounding water molecules and its solvation dynamics show unique features. Because of an extended positive charge distribution, metformin possesses features of being a permanent cationic partner toward several targets. We study its interaction and binding ability with DNA using UV spectroscopy, circular dichroism, fluorimetry and metadynamics simulation. We find a non-intercalating mode of interaction. Metformin feasibly forms a minor/major groove-bound state within a few tens of nanoseconds, preferably with AT rich domains. A significant decrease in the free-energy of binding is observed when it binds to a minor groove of DNA.Comment: 60 pages, 24 figure

Synthesis, structure and ionic conductivity in scheelite type Li_0.5Ce_0.5-xLn_xMoO₄ (x = 0 and 0.25, Ln = Pr, Sm)

Scheelite type solid electrolytes, Li0.5Ce0.5-xLnxMoO4 (x = 0 and 0.25, Ln = Pr, Sm) have been synthesized using a solid state method. Their structure and ionic conductivity (σ) were obtained by single crystal X-ray diffraction and ac-impedance spectroscopy, respectively. X-ray diffraction studies reveal a space group of I41/a for Li0.5Ce0.5-xLnxMoO4 (x = 0 and 0.25, Ln = Pr, Sm) scheelite compounds. The unsubstituted Li0.5Ce0.5-xLnxMoO4 showed lithium ion conductivity ∼10−5-10−3 Ω−1cm−1 in the temperature range of 300-700°C (σ = 2.5 × 10−3 Ω−1cm−1 at 700°C). The substituted compounds show lower conductivity compared to the unsubstituted compound, with the magnitude of ionic conductivity being two (in the high temperature regime) to one order (in the low temperature regime) lower than the unsubstituted compound. Since these scheelite type structures show significant conductivity, the series of compounds could serve in high temperature lithium battery operations

A single cation or anion dendrimer-based liquid electrolyte

We propose here a novel liquid dendrimer-based single ion conductor as a potential alternative to conventional molecular liquid solvent-salt solutions in rechargeable batteries, sensors and actuators. A specific change from ester (-COOR) to cyano (-CN) terminated peripheral groups in generation-one poly(propyl ether imine) (G1-PETIM)-lithium salt complexes results in a remarkable switchover from a high cation (tLi+ = 0.9 for -COOR) to a high anion (tPF6- = 0.8 for -CN) transference number. This observed switchover draws an interesting analogy with the concept of heterogeneous doping, applied successfully to account for similar changes in ionic conductivity arising out of dispersion of insulator particle inclusions in weak inorganic solid electrolytes. The change in peripheral group simultaneously affects the effective ionic conductivity, with the room temperature ionic conductivity of PETIM-CN (1.9 × 10-5 Ω-1 cm-1) being an order of magnitude higher than PETIM-COOR (1.9 × 10-6 Ω-1 cm-1). Notably, no significant changes are observed in the lithium mobility even following changes in viscosity due to the change in the peripheral group. Changes in the peripheral chemical functionality directly influence the anion mobility, being lower in PETIM-COOR than in PETIM-CN, which ultimately becomes the sole parameter controlling the effective transport and electrochemical properties of the dendrimer electrolytes

N7-(carboxymethyl)guanine-lithium crystalline complex: a bioinspired solid electrolyte

Electrochemical device with components having direct significance to biological life processes is a potent futuristic strategy for the realization of all-round green and sustainable development. We present here synthesis design, structural analysis and ion transport of a novel solid organic electrolyte (G7Li), a compound reminiscent of ion channels, derived from regioisomeric N7-guanine-carboxylate conjugate and Li-ions. G7Li, with it\u27s in-built supply of Li(+)-ions, exhibited remarkably high lithium-ion transference number (= 0.75) and tunable room temperature ionic conductivity spanning three decades (≈10(-7) to 10(-3) Ω(-1) cm(-1)) as a function of moisture content. The ionic conductivity show a distinct reversible transition around 80-100 °C, from a dual Li(+) and H(+) (<100 °C) to a pure Li(+) conductor (>100 °C). Systematic studies reveal a transition from water-assisted Li-ion transport to Li hopping-like mechanism involving guanine-Li coordination. While as-synthesized G7Li has potential in humidity sensors, the anhydrous G7Li is attractive for rechargeable batteries

Holographic GB gravity in arbitrary dimensions

We study the properties of the holographic CFT dual to Gauss-Bonnet gravity in general $D \ge 5$ dimensions. We establish the AdS/CFT dictionary and in particular relate the couplings of the gravitational theory to the universal couplings arising in correlators of the stress tensor of the dual CFT. This allows us to examine constraints on the gravitational couplings by demanding consistency of the CFT. In particular, one can demand positive energy fluxes in scattering processes or the causal propagation of fluctuations. We also examine the holographic hydrodynamics, commenting on the shear viscosity as well as the relaxation time. The latter allows us to consider causality constraints arising from the second-order truncated theory of hydrodynamics.Comment: 48 pages, 9 figures. v2: New discussion on free fields in subsection 3.3 and new appendix B on conformal tensor fields. Added comments on the relation between the central charge appearing in the two-point function and the "central charge" characterizing the entropy density in the discussion. References adde

Holographic Hydrodynamics with a Chemical Potential

We consider five-dimensional gravity coupled to a negative cosmological constant and a single U(1) gauge field, including a general set of four-derivative interactions. In this framework, we construct charged planar AdS black hole solutions perturbatively and consider the thermal and hydrodynamic properties of the plasma in the dual CFT. In particular, we calculate the ratio of shear viscosity to entropy density and argue that the violation of the KSS bound is enhanced in the presence of a chemical potential. We also compute the electrical conductivity and comment on various conjectured bounds related to this coefficient.Comment: v2: comparison to supergravity lagrangian added, references added, typos fixe

Ion Transport in Liquid Salt Solutions with Oxide Dispersions:``Soggy Sand'' Electrolytes

``Soggy sand'' electrolyte, which essentially consists of oxide dispersions in nonaqueous liquid salt solutions, comprises an important class of soft matter electrolytes. The ion transport mechanism of soggy sand electrolyte is complex. The configuration of particles in the liquid solution has been observed to depend in a nontrivial manner on various parameters related to the oxide (concentration, size, surface chemistry) and solvent (dielectric constant, viscosity) as well as time. The state of the particles in solution not only affects ionic conductivity but also effectively the mechanical and electrochemical properties of the solid liquid composite. Apart from comprehensive understanding of the underlying phenomena that govern ion transport, which will benefit design of better electrolytes, the problem has far-reaching implications in diverse fields such as catalysis, colloid chemistry, and biotechnology

Influence of water and thermal history on ion transport in lithium salt-succinonitrile plastic crystalline electrolytes

Important issues of water and thermal history affecting ion transport in a representative plastic crystalline lithium salt electrolyte: succinonitrile (SN)–lithium perchlorate (LiClO₄) are discussed here. Ionic conductivity of electrolytes with high lithium salt amounts (∼1 M) in SN at a particular temperature is known to be influenced both by the trans–gauche isomerism and ion association (solvation), the two most important intrinsic parameters of the plastic solvent. In the present study both water and thermal history influence SN and result in enhancement of ionic conductivity of 1 M LiClO₄–SN electrolyte. Systematic observations reveal that the presence of water in varying amounts promote ion-pair dissociation in the electrolyte. While trace amounts (≈1–15 ppm) do not affect the trans–gauche isomerism of SN, the presence of water in large amounts (≈5500 ppm) submerges the plasticity of SN. Subjugating the electrolyte to different thermal protocol resulted in enhancement of trans concentration only. This is an interesting observation as it demonstrates a simple and effective procedure involving utilization of an optimized set of external parameters to decouple solvation from trans–gauche isomerism. Observations from the ionic conductivity of various samples were accounted by changes in signature isomer and ion-association bands in the mid-IR regime and also from plastic to normal crystal transition temperature peak obtained from thermal studies

Antimony sulphoiodide (SbSI), a narrow band-gap non-oxide ternary semiconductor with efficient photocatalytic activity

In the context of the harvesting of solar photons, one dimensional semiconductors are attractive as they provide uninterrupted transport pathways for charge carriers, along the covalently bonded atomic chain direction. Moreover, the one-dimensional growth leads to a lower proportion of dangling bonds at the surfaces due to preferential growth in a particular direction. We report here a non-metal oxide semiconductor, antimony sulphoiodide (SbSI) which displays high optical absorption and a low and tunable band gap for visible light photocatalytic applications. Highly crystalline 1-D micro-rods of SbSI which eventually self-assemble into 3-D ``urchin''-shaped structures are synthesized by using a simple solution method. The morphology of the SbSI is studied in terms of the dangling bonds at the surface planes. The results conclusively show that the SbSI has a lower proportion of dangling bonds at the surface. The electronic structure of SbSI, studied using density functional theory, displays a large static dielectric constant due to the ns(2) cation (Sb3+) which enhances the separation of electron and hole pairs effectively. The combination of these two features makes SbSI a promising material for visible photocatalytic degradation of organic pollutants in water, in spite of an overall low surface area (approximate to 2.6 m(2) g(-1))