Mine Yurtsever

A dft study of polymerization mechanisms of indole

Abstract Polymerization of unsubstituted indoles is studied by accurate density functional theory calculations. Relative stability of all possible dimers of indole is computed in order to understand the thermodynamics of polymerization. It is observed that 2-position is the most likely site to enhance polymerization. A selected set of trimers and tetramers which use a 2-position for linkages are generated to understand the further growth of polyindole. A study of local minima arising from different distributions of the torsional angles reveals that there are two equally probable conformations and the one with the torsional angle changing signs alternatively is slightly favored. The cyclic structures are also investigated and it is shown that it is possible to generate stable three- and four-membered cyclic structures. Finally, the structures of radical cations and intermediate states are fully optimized and the energetics of these metastable species are used to explain the competing mechanisms of radical–radical and radical–neutral pathways.

Bosonic helium droplets with cationic impurities : Onset of electrostriction and snowball effects from quantum calculations

Variational Monte Carlo and diffusion Monte Carlo calculations have been carried out for cations such as Li(+), Na(+), and K(+) as dopants of small helium clusters over a range of cluster sizes up to about 12 solvent atoms. The interaction has been modeled through a sum-of-potential picture that disregards higher order effects beyond atom-atom and atom-ion contributions. The latter were obtained from highly correlated ab initio calculations over a broad range of interatomic distances. This study focuses on two of the most striking features of the microsolvation in a quantum solvent of a cationic dopant: electrostriction and snowball effects. They are discussed here in detail and in relation with the nanoscopic properties of the interaction forces at play within a fully quantum picture of the cluster features.

Tetrameric Iridium Hydride-Rich Clusters Formed under Hydrogenation Conditions**

Asymmetric hydrogenation using iridium catalysts has been recognized as an important alternative to rhodium catalysis in recent years, because it enables the creation of a new stereogenic center without reliance on polar functionality in the substrate. Previous study of Ir hydrogenations provided significant insights into the mechanism, and underscored that an important deactivation process involves the formation of catalytically inactive trimers. The formation of such species may be limited by a judicious choice of nitrogen and phosphorus ligands, which leads to a new family of active catalysts. Herein, we highlight a quite different aspect of these studies. Hydrogenation of a specific iridium procatalyst under substrate free conditions leads not only to trimers but also higher nuclearity hydride-rich cluster compounds of iridium. Weller and McIndoe demonstrated that hydride-rich cluster compounds of rhodium have interesting structural and chemical features, but the corresponding compounds of iridium have not previously been studied. Herein, we describe the unique structures of two tetrameric hydriderich iridium clusters which are formed irreversibly under substrate-free conditions, in addition to a conventional trimer, as previously described (Scheme 1). The research suggests an important general route to this class of cluster compounds, because the nuclearities of the clusters formed under these conditions may in future be fine-tuned by varying the steric and electronic properties of the ligands. Hydrogenation of complex 1 ([Ir(PCy3)(cod)(C9H11N)] PF6) in CD2Cl2 was monitored by H NMR spectroscopy, until the reduction of 1,5-cyclooctadiene (cod) was complete. At this stage, the H NMR spectrum showed a complex iridium hydride region, in which the species 2 (an analogue of the dicationic Crabtree trimer) was detected, although it provided 40 % of the total signal intensity. The high resolution electrospray (ES) mass spectrum of solutions analyzed after complete reduction also revealed the presence of the standard trimer [Ir3H7(PCy3)3(C9H11N)3] 2+ (2), and an ion formed by loss of one N ligand from 2. In addition, two strong peaks corresponding to [Ir4H10(PCy3)4(C9H11N)2] 2+ (3a) and [Ir4H11(PCy3)4(C9H11N)] + (3b) were observed. Both of these gave characteristic patterns based on the stable isotope ratio (Ir/Ir = 37.3:62.7), providing unambiguous confirmation of the cation formulae (Figure 1). The structure obtained by single-crystal X-ray diffraction, after very slow crystallization of the hydrogenation product from dichloromethane/pentane, corresponds to the complex 3a, [Ir4H10(Cy3P)4(C9H11N)2] 2+ (PF6 )2. [5] The hydrogen atoms could not be located in the difference map, owing to the close proximity of heavy atoms and the associated termination Scheme 1. Hydrogenation of complex 1 under ambient substrate-free conditions.

Investigation of Inhibition Mechanism of Chemokine Receptor CCR5 by Micro-second Molecular Dynamics Simulations

Chemokine receptor 5 (CCR5) belongs to G protein coupled receptors (GPCRs) and plays an important role in treatment of human immunodeficiency virus (HIV) infection since HIV uses CCR5 protein as a co-receptor. Recently, the crystal structure of CCR5-bound complex with an approved anti-retroviral drug (maroviroc) was resolved. During the crystallization procedure, amino acid residues (i.e., Cys224, Arg225, Asn226 and Glu227) at the third intra-cellular loop were replaced by the rubredoxin for stability reasons. In the current study, we aimed to understand the impact of the incorporated rubredoxin on the conformations of TM domains of the target protein. For this reason, rubredoxin was deleted from the crystal structure and the missing amino acids were engineered. The resultant structure was subjected to long (μs) molecular dynamics (MD) simulations to shed light into the inhibitory mechanism. The derived model structure displayed a significant deviation in the cytoplasmic domain of TM5 and IC3 in the absence of rubredoxin. The principal component analyses (PCA) and MD trajectory analyses revealed important structural and dynamical differences at apo and holo forms of the CCR5.

Structural studies of polypyrroles: I. An ab-initio evaluation of bonding through α and β carbons

Detailed ab-initio calculations of a number of pyrrole oligomers are carried out in order to find out relative stability of structures bonded through α and β carbons. Energetics of dimers, trimers and tetramers with all possible linkage types and several pentamers are obtained from fully optimized geometry. The linear as well as the branched forms of tetramers and pentamers are compared so that probabilities of branching can be estimated. The energy differences of different types of structures suggest that a great deal of branching is probable. It is shown that relative energies of 65 oligomers can be fairly reproduced by a simple partitioning in terms of monomer types. The approximate probability function generated in this manner is used in the following paper in a statistical mechanical approach to estimate the extent of bonding involving β carbons as well as branching in polypyrroles.

Structural studies of polypyrroles: II. A Monte Carlo growth approach to the branch formation

Abstract A simulation technique which is based on quantum mechanically generated probability distributions of αα, αβ and ββ type linkages in polypyrroles is presented and applied for a statistical analysis of the growth process. The results show that the branching occur even at very short chains. The extent of the branching does not depend on the chain length and it is a slowly varying function of the temperature. At room temperatures, 20–25% deviations from the linearity is observed which is consistent with the experimental observations.

Binding Interactions of Dopamine and Apomorphine in D2High and D2Low States of Human Dopamine D2 Receptor Using Computational and Experimental Techniques

We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model.

Modeling and protein engineering studies of active and inactive states of human dopamine D2 receptor (D2R) and investigation of drug/receptor interactions

Homology model structures of the dopamine D2 receptor (D2R) were generated starting from the active and inactive states of

Atomistic molecular dynamics simulations of typical and atypical antipsychotic drugs at the dopamine D2 receptor (D2R) elucidates their inhibition mechanism

\upbeta