3 research outputs found

    Role of Molecular Dipoles in Charge Transport across Large Area Molecular Junctions Delineated Using Isomorphic Self-Assembled Monolayers

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    Delineating the role of dipoles in large area junctions that are based on self-assembled monolayers (SAMs) is challenging due to molecular tilt, surface defects, and interchain coupling among other features. To mitigate SAM-based effects in study of dipoles, we investigated tunneling rates across carboranesisostructural molecules that orient along the surface normal on Au (but bear different dipole moments) without changing the thickness, packing density, or morphology of the SAM. Using the Au-SAM//Ga<sub>2</sub>O<sub>3</sub>-EGaIn junction (where “//” = physisorption, “–” = chemisorption, and EGaIn is eutectic gallium–indium), we observe that molecules with dipole moments oriented along the surface normal (with dipole moment, <i>p</i> = 4.1D for both M9 and 1O2) gave lower currents than when the dipole is orthogonal (<i>p</i> = 1.1 D, M1) at ±0.5 V applied bias. Similarly, from transition voltage spectroscopy, the transition voltages, <i>V</i><sub>T</sub> (volt), are significantly different. (0.5, 0.43, and 0.4 V for M1, M9, and 1O2, respectively). We infer that the magnitude and direction of a dipole moments significantly affect the rate of charge transport across large area junctions with Δ log|J| ≅ 0.4 per Debye. This difference is largely due to effect of the dipole moment on the molecule-electrode coupling strength, Γ, hence effect of dipoles is likely to manifest in the contact resistance, <i>J</i><sub>o</sub>, although in conformational flexible molecules field-induced effects are expected

    Exploring the Catalytic Mechanism of Alkanesulfonate Monooxygenase Using Molecular Dynamics

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    The complex mechanistic properties of alkanesulfonate monooxygenase (SsuD) provide a particular challenge for identifying catalytically relevant amino acids. In response, a joint computational and experimental study was conducted to further elucidate the SsuD mechanism. Extensive unbiased molecular dynamics (MD) simulations were performed for six SsuD systems: (1) substrate-free, (2) bound with FMNH<sub>2</sub>, (3) bound with a C4a-peroxyflavin intermediate (FMNOO<sup>–</sup>), (4) bound with octanesulfonate (OCS), (5) co-bound with FMNH<sub>2</sub> and OCS, and (6) co-bound with FMNOO<sup>–</sup> and OCS. A previous theoretical study suggested that salt bridges between Arg297 and Glu20 or Asp111 initiated conformational changes critical for catalysis. However, our MD simulations and steady-state kinetic experiments did not corroborate this result. Similar <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> values for both the E20A and D111A SsuD variants to wild-type SsuD suggest that the salt bridges are not critical to the desulfonation mechanism. Instead, the predicted role of Arg297 is to favorably interact with the phosphate group of the reduced flavin. Concomitantly, Arg226 functioned as a “protection” group shielding FMNOO<sup>–</sup> from bulk solvent and was more pronounced when both FMNOO<sup>–</sup> and OCS were bound. The stabilization of FMNOO<sup>–</sup> through electrostatic interactions with Arg226 would properly position the C4a peroxy group for the proposed nucleophilic attack on the sulfur of octanesulfonate

    Determination of antiplasmodial activity and binding affinity of curcumin and demethoxycurcumin towards <i>Pf</i>TrxR

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    <div><p>In our study, the inhibitory activity of curcuminoids towards <i>Plasmodium falciparum</i> thioredoxin reductase (<i>Pf</i>TrxR) was determined using LC-MS-based functional assay and showed that only demethoxycurcumin (DMC) inhibited <i>Pf</i>TrxR (IC<sub>50</sub>: 2 μM). <i>In silico</i> molecular modelling was used to ascertain and further confirm that the binding affinities of curcumin and DMC are towards the dimer interface of <i>Pf</i>TrxR. The <i>in vitro</i> antiplasmodial activities of curcumin and DMC were evaluated and shown to be active against chloroquine (CQ)-sensitive (D6 clone) and moderately active against CQ-resistant (W2 clone) strains of <i>Plasmodium falciparum</i> while no cytotoxicity was observed against Vero cells.</p></div