Structures and energetics of darunavir and active site amino acids of native and mutant HIV–1 protease: a computational study

Structural Chemistry - Quantum chemical calculations have been performed at the M06–2X/6–31G(d,p) level of theory to investigate the strength and nature of interactions between the...     

Reciprocal Ontological Models Show Indeterminism Comparable to Quantum Theory

We show that within the class of ontological models due to Harrigan and Spekkens, those satisfying preparation-measurement reciprocity must allow indeterminism comparable to that in quantum theory. Our result implies that one can design quantum random number generator, for which it is impossible, even in principle, to construct a reciprocal deterministic model.     

Solid-State Isolation of Cyclic Alkyl(Amino) Carbene (cAAC)-Supported Structurally Diverse Alkali Metal-Phosphinidenides

Cyclic alkyl(amino) carbene (cAAC)-supported, structurally diverse alkali metal-phosphinidenides 2 – 5 of general formula ((cAAC)P-M)_n(THF)_x [ 2 : M=K, n=2, x=4; 3 : M=K, n=6, x=2; 4 : M=K, n=4, x=4; 5 : M=Na, n=3, x=1] have been synthesized by the reduction of cAAC-stabilized chloro-phosphinidene cAAC=P-Cl ( 1 ) utilizing metallic K or KC₈ and Na-naphthalenide as reducing agents. Complexes 2 – 5 have been structurally characterized in solid state by NMR studies and single crystal X-ray diffraction. The proposed mechanism for the electron transfer process has been well-supported by cyclic voltammetry (CV) studies and Density Functional Theory (DFT) calculations. The solid state oligomerization process has been observed to be largely dependent on the ionic radii of alkali metal ions, steric bulk of cAAC ligands and solvation/de-solvation/recombination of the dimeric unit [(cAAC)P-M(THF)_x]₂.     

Synchrotron X‐ray phase contrast imaging of leaf venation in soybean (Glycine max) after exclusion of solar UV (280–400 nm) radiation

The hydraulic efficiency of a leaf depends on its vascular structure as this is responsible for transport activities. To investigate the effect of exclusion of UVAB and UVB radiation from the solar spectrum on the micro‐structure of leaves of soybean (Glycine max, variety JS‐335), a field experiment was conducted using synchrotron‐based phase contrast imaging (PCI). Plants were grown in specially designed UV exclusion chambers, and wrapped with filters that excluded UVB (280–315 nm) or UVAB (280–400 nm), or transmitted all the ambient solar UV (280–400 nm) radiation (filter control). Qualitative observation of high‐resolution X‐ray PCI images obtained at 10 keV has shown the differences in major and minor vein structures of the leaves. The mid‐rib width of the middle leaflet of third trifoliate leaves, for all treatments, were obtained using quantitative image analysis. The width of the mid‐rib of the middle leaflet of third trifoliate leaves of UVB excluded plants was found to be more compared to leaves of filter control plants, which are exposed to ambient UV. The mid‐rib or the main conducting vein transports water and sugars to the whole plant; therefore, mid‐rib enhancement by the exclusion of solar UV radiation possibly implies enhancement in the leaf area which in turn causes an increased rate of photosynthesis.     

Closed geodesics on orbifolds

In this paper, we try to generalize to the case of compact Riemannian orbifolds Q some classical results about the existence of closed geodesics of positive length on compact Riemannian manifolds M. We shall also consider the problem of the existence of infinitely many geometrically distinct closed geodesics.In the classical case the solution of those problems involve the consideration of the homotopy groups of M and the homology properties of the free loop space on M (Morse theory). Those notions have their analogue in the case of orbifolds. The main part of this paper will be to recall those notions and to show how the classical techniques can be adapted to the case of orbifolds.     

Homology modeling of 5-lipoxygenase and hints for better inhibitor design

Lipoxygenases (LOXs) are a group of enzymes involved in the oxygenation of polyunsaturated fatty acids. Among these 5-lipoxygenase (5-LOX) is the key enzyme leading to the formation of pharmacologically important leukotrienes and lipoxins, the mediators of inflammatory and allergic disorders. In view of close functional similarity to mammalian lipoxygenase, potato 5-LOX is used extensively. In this study, the homology modeling technique has been used to construct the structure of potato 5-LOX. The amino acid sequence identity between the target protein and sequence of template protein 1NO3 (soybean LOX-3) searched from NCBI protein BLAST was 63%. Based on the template structure, the protein model was constructed by using the Homology program in InsightII. The protein model was briefly refined by energy minimization steps and validated using Profile-3D, ERRAT and PROCHECK. The results showed that 99.3% of the amino acids were in allowed regions of Ramachandran plot, suggesting that the model is accurate and its stereochemical quality good. Like all LOXs, 5-LOX also has a two-domain structure, the small N-terminal beta-barrel domain and a larger catalytic domain containing a single atom of non-heme iron coordinating with His525, His530, His716 and Ile864. Asn720 is present in the fifth coordination position of iron. The sixth coordination position faces the open cavity occupied here by the ligands which are docked. Our model of the enzyme is further validated by examining the interactions of earlier reported inhibitors and by energy minimization studies which were carried out using molecular mechanics calculations. Four ligands, nordihydroguaiaretic acid (NDGA) having IC(50) of 1.5 microM and analogs of benzyl propargyl ethers having IC(50) values of 760 microM, 45 microM, and no inhibition respectively were selected for our docking and energy minimization studies. Our results correlated well with the experimental data reported earlier, which proved the quality of the model. This model generated can be further used for the design and development of more potent 5-LOX inhibitors.     

Evaluation of polysaccharide-based chiral stationary phases in quality control of (S)-mirtazapine

High-performance liquid chromatographic methods were developed for separation of the enantiomers of mirtazapine and its four process-related substances. The direct separations were achieved on chiral stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H), cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and cellulose tris(4-methylbenzoate) (Chiralcel OJ-H ). The experimental data were utilized to discuss the effects of the mobile phase composition, the nature of the alcoholic modifier and the specific structural features of the analytes on retention and separation. The elution sequence was determined under the optimized separation conditions.