Enantiomeric Separation and Molecular Modelling of Bioactive 4-aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase

The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios (α > 2) in contrast with the smaller α values (1–1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy α values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-d-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand d-Ala-d-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors.

First Principles Study of Ga₍₂₀₋x₎Alx⁺ Nanoalloys: Structure, Thermodynamics and Phase Diagram

<p>Nanoalloys (a finite framework of two or more metal atoms) represent a rapidly growing field owing to the possibilities of tuning its properties as desired for various applications. Their properties are size, shape, composition, chemical ordering, and temperature dependent, thereby offering a large playground for varied research motivations. This thesis documents the investigations on how the addition of aluminium affects the cationic gallium clusters, both in terms of geometric & electronic structure and thermodynamics, which have been observed to show greater-than-bulk melting behaviour for small sizes. A specific cluster size of 20 atoms is selected, Ga₍₂₀₋x₎Alx⁺, with the overall intention of creating a phase diagram which is the most reliable way to predict the phase changes in the system. All the first principles (density functional theory) based Born-Oppenheimer molecular dynamics calculations have been performed in the microcanonical ensemble. Melting behaviour is first studied in the pure Al₂₀⁺ clusters and then in three representative clusters of Ga₍₂₀₋x₎Alx⁺ series: Ga₁₉Al⁺, Ga₁₁Al₉⁺ and Ga₃Al₁₇⁺ clusters. We observe that all the three nanoalloy compositions show greater-than-bulk melting behaviour behaviour as well and in Ga₁₉Al⁺, specifically, Al prefers the internal sites, contrary to the previous arguments. We go on to complete the solid-liquid-like melting phase diagram using the calculated information and further propose a model of these greater-than-bulk melting clusters to be components of the corresponding bulk phases, whether metals or alloys, with additional size-dependent contributions added to it.</p>

First Principles Study of Ga₍₂₀₋x₎Alx⁺ Nanoalloys: Structure, Thermodynamics and Phase Diagram

<p>Nanoalloys (a finite framework of two or more metal atoms) represent a rapidly growing field owing to the possibilities of tuning its properties as desired for various applications. Their properties are size, shape, composition, chemical ordering, and temperature dependent, thereby offering a large playground for varied research motivations. This thesis documents the investigations on how the addition of aluminium affects the cationic gallium clusters, both in terms of geometric & electronic structure and thermodynamics, which have been observed to show greater-than-bulk melting behaviour for small sizes. A specific cluster size of 20 atoms is selected, Ga₍₂₀₋x₎Alx⁺, with the overall intention of creating a phase diagram which is the most reliable way to predict the phase changes in the system. All the first principles (density functional theory) based Born-Oppenheimer molecular dynamics calculations have been performed in the microcanonical ensemble. Melting behaviour is first studied in the pure Al₂₀⁺ clusters and then in three representative clusters of Ga₍₂₀₋x₎Alx⁺ series: Ga₁₉Al⁺, Ga₁₁Al₉⁺ and Ga₃Al₁₇⁺ clusters. We observe that all the three nanoalloy compositions show greater-than-bulk melting behaviour behaviour as well and in Ga₁₉Al⁺, specifically, Al prefers the internal sites, contrary to the previous arguments. We go on to complete the solid-liquid-like melting phase diagram using the calculated information and further propose a model of these greater-than-bulk melting clusters to be components of the corresponding bulk phases, whether metals or alloys, with additional size-dependent contributions added to it.</p>

An overview of thermotransport in fluorite-related ionic oxides

In this overview, we summarize the phenomenon of thermotransport (the close coupling of mass transport and heat transport) in two fast ion conductors: yttria-doped zirconia and gadolinia-doped ceria. We focus on two recent molecular dynamics calculations using the Green-Kubo formalism. We show that the Onsager thermotransport cross coefficient (mass-heat coupling) is negative, meaning that oxygen ions would drift, in principle, to the hot side in a temperature gradient. Simulation results presented in this overview show reasonable agreement with available experimental data for thermal conductivity. Results of this study suggest that the coupling between mass and heat transport in oxygen ion electrolytes could have significant effect for practical applications.

Nanosecond heme-to-heme electron transfer rates in a multiheme cytochrome nanowire reported by a spectrally unique His/Met-ligated heme

Proteins achieve efficient energy storage and conversion through electron transfer along a series of redox cofactors. Multiheme cytochromes are notable examples. These proteins transfer electrons over distance scales of several nanometers to >10 μm and in so doing they couple cellular metabolism with extracellular redox partners including electrodes. Here, we report pump-probe spectroscopy that provides a direct measure of the intrinsic rates of heme–heme electron transfer in this fascinating class of proteins. Our study took advantage of a spectrally unique His/Met-ligated heme introduced at a defined site within the decaheme extracellular MtrC protein of Shewanella oneidensis. We observed rates of heme-to-heme electron transfer on the order of 109 s−1 (3.7 to 4.3 Å edge-to-edge distance), in good agreement with predictions based on density functional and molecular dynamics calculations. These rates are among the highest reported for ground-state electron transfer in biology. Yet, some fall 2 to 3 orders of magnitude below the Moser–Dutton ruler because electron transfer at these short distances is through space and therefore associated with a higher tunneling barrier than the through-protein tunneling scenario that is usual at longer distances. Moreover, we show that the His/Met-ligated heme creates an electron sink that stabilizes the charge separated state on the 100-μs time scale. This feature could be exploited in future designs of multiheme cytochromes as components of versatile photosynthetic biohybrid assemblies.

Can We Predict the Isosymmetric Phase Transition? Application of DFT Calculations to Study the Pressure Induced Transformation of Chlorothiazide

Isosymmetric structural phase transition (IPT, type 0), in which there are no changes in the occupation of Wyckoff positions, the number of atoms in the unit cell, and the space group symmetry, is relatively uncommon. Chlorothiazide, a diuretic agent with a secondary function as an antihypertensive, has been proven to undergo pressure-induced IPT of Form I to Form II at 4.2 GPa. For that reason, it has been chosen as a model compound in this study to determine if IPT can be predicted in silico using periodic DFT calculations. The transformation of Form II into Form I, occurring under decompression, was observed in geometry optimization calculations. However, the reverse transition was not detected, although the calculated differences in the DFT energies and thermodynamic parameters indicated that Form II should be more stable at increased pressure. Finally, the IPT was successfully simulated using ab initio molecular dynamics calculations.