Topological alterations in human spermatozoa associated with the polyelectrolytic effect of RISUG

A new method of male contraception has been developed which results in long-term infertility and has the potential advantage of being reversible. The contraceptive, given the name RISUG (an acronym for Reversible Inhibition of Sperm Under Guidance) is a polyelectrolytic compound and when injected into the lumen of the vas deferens, induces a surface charge imbalance on the sperm membrane system leading to its destabilization. In the present study, morphological and topological alterations in human spermatozoa induced by RISUG have been investigated using atomic force microscopy (AFM). Complete disintegration of the plasma membrane with subsequent rupture and dispersion of the acrosomal contents is observed on treatment with RISUG in vitro. Considerable damage to the midpiece region with significant clustering of the mitochondria and its fusion with the head region is also observed. These observations are in agreement with the significant increase in the volume of RISUG-treated sperm-head region. Topological alterations in the flagellar and midpiece region of RISUG-treated spermatozoa have also been studied.     

Synthesis and surface properties of environmentally responsive segmented polyurethanes

Polyurethanes, containing well-defined assemblies of perfluoro-polyether (PFPE or hexafluoropropene oxide oligomer), polydimethylsiloxane (PDMS), and polyethylene glycol (PEG) segments, exhibit oleophobic, hydrophobic, and hydrophilic properties in response to the polarity of the contacting medium. These polymers were prepared by reacting hydroxy(polyethyleneoxy)-propylether-terminated PDMS block copolymer (HO-PEG-PDMS-PEG-OH) with 4,4'-methylene-bis(phenylene isocyanate) (MDI) in the presence of dibutyltin dilaurate catalyst, followed by reaction with 1,2-diol functional PFPE and chain extension with 2,2,3,3-tetrafluoro-1,4-butanediol (FB). The oleophobic and hydrophobic properties of the segmented polyurethanes (SPU) are due to the segregation of PFPE segments at the polymer-air interface. Wettability studies revealed that the same surface becomes hydrophilic, presumably due to the segregation of the PEG segments at the polymer-water interface. This hydrophobic-to-hydrophilic transformation of the surface prevails not only when the polymer is in contact with liquid water but with water vapor as well. The understanding of the reconstruction mechanism of this novel family of SPU surfaces would furnish valuable information for various applications where dynamic transformation of surface activity is desired.     

Structural,spectroscopic aspects,and electronic properties of (TiO2)n clusters: A study based on the use of natural algorithms in association with quantum chemical methods

In this article, we propose a stochastic search‐based method, namely genetic algorithm (GA) and simulated annealing (SA) in conjunction with density functional theory (DFT) to evaluate global and local minimum structures of (TiO₂)_n clusters with n = 1–12. Once the structures are established, we evaluate the infrared spectroscopic modes, cluster formation energy, vertical excitation energy, vertical ionization potential, vertical electron affinity, highest occupied molecular orbital (HOMO)‐lowest unoccupied molecular orbital (LUMO) gaps, and so forth. We show that an initial determination of structure using stochastic techniques (GA/SA), also popularly known as natural algorithms as their working principle mimics certain natural processes, and following it up with density functional calculations lead to high‐quality structures for these systems. We have shown that the clusters tend to form three‐dimensional networks. We compare our results with the available experimental and theoretical results. The results obtained from SA/GA‐DFT technique agree well with available theoretical and experimental data of literature. © 2013 Wiley Periodicals, Inc.     

Exploring polypharmacology using a ROCS-based target fishing approach

Polypharmacology has emerged as a new theme in drug discovery. In this paper, we studied polypharmacology using a ligand-based target fishing (LBTF) protocol. To implement the protocol, we first generated a chemogenomic database that links individual protein targets with a specified set of drugs or target representatives. Target profiles were then generated for a given query molecule by computing maximal shape/chemistry overlap between the query molecule and the drug sets assigned to each protein target. The overlap was computed using the program ROCS (Rapid Overlay of Chemical Structures). We validated this approach using the Directory of Useful Decoys (DUD). DUD contains 2950 active compounds, each with 36 property-matched decoys, against 40 protein targets. We chose a set of known drugs to represent each DUD target, and we carried out ligand-based virtual screens using data sets of DUD actives seeded into DUD decoys for each target. We computed Receiver Operator Characteristic (ROC) curves and associated area under the curve (AUC) values. For the majority of targets studied, the AUC values were significantly better than for the case of a random selection of compounds. In a second test, the method successfully identified off-targets for drugs such as rimantadine, propranolol, and domperidone that were consistent with those identified by recent experiments. The results from our ROCS-based target fishing approach are promising and have potential application in drug repurposing for single and multiple targets, identifying targets for orphan compounds, and adverse effect prediction.     

Comparison between self-guided Langevin dynamics and molecular dynamics simulations for structure refinement of protein loop conformations

This article presents a comparative analysis of two replica‐exchange simulation methods for the structure refinement of protein loop conformations, starting from low‐resolution predictions. The methods are self‐guided Langevin dynamics (SGLD) and molecular dynamics (MD) with a Nosé–Hoover thermostat. We investigated a small dataset of 8‐ and 12‐residue loops, with the shorter loops placed initially from a coarse‐grained lattice model and the longer loops from an enumeration assembly method (the Loopy program). The CHARMM22 + CMAP force field with a generalized Born implicit solvent model (molecular‐surface parameterized GBSW2) was used to explore conformational space. We also assessed two empirical scoring methods to detect nativelike conformations from decoys: the all‐atom distance‐scaled ideal‐gas reference state (DFIRE‐AA) statistical potential and the Rosetta energy function. Among the eight‐residue loop targets, SGLD out performed MD in all cases, with a median of 0.48 Å reduction in global root‐mean‐square deviation (RMSD) of the loop backbone coordinates from the native structure. Among the more challenging 12‐residue loop targets, SGLD improved the prediction accuracy over MD by a median of 1.31 Å, representing a substantial improvement. The overall median RMSD for SGLD simulations of 12‐residue loops was 0.91 Å, yielding refinement of a median 2.70 Å from initial loop placement. Results from DFIRE‐AA and the Rosetta model applied to rescoring conformations failed to improve the overall detection calculated from the CHARMM force field. We illustrate the advantage of SGLD over the MD simulation model by presenting potential‐energy landscapes for several loop predictions. Our results demonstrate that SGLD significantly outperforms traditional MD in the generation and populating of nativelike loop conformations and that the CHARMM force field performs comparably to other empirical force fields in identifying these conformations from the resulting ensembles. Published 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Motion of drops on a surface induced by thermal gradient and vibration

It is well known that a liquid drop with a low contact angle (approximately 45 degrees ) and low wetting hysteresis moves toward the colder region of a temperature gradient substrate as a result of the thermal Marangoni force. A moderately sized water drop, however, usually does not move on such a surface because of the overwhelming effect of hysteresis. The water drop can, however, be forced to move when it is vibrated on a temperature gradient surface with its velocity exhibiting maxima at the respective Rayleigh frequencies. A simple model is presented that captures the dependence of drop velocity on hysteresis, vibration amplitude, and the forcing and resonance frequencies of vibration.     

Bi- and trinuclear copper(II) complexes of a sterically constrained phenol-based tetradentate ligand: syntheses, structures, and magnetic studies

Copper(II) complexes (1-3) of a sterically constrained phenol-based tetradentate N(2)O(2) ligand 1,4-bis(2-hydroxy-3,5-dimethylbenzyl)piperazine (H(2)L) have been reported. The associated anions of the copper(II) ion precursors have profound influence on the stoichiometry of the products. Thus, with perchlorate ion, the product is a binuclear compound [Cu(2)L(2)] (1), while with coordinating anions viz. Cl(-) and N(3)(-), the products [Cu(3)L(2)Cl(2)(H(2)O)].1/2H(2)L (2) and [Cu(3)L(2)(N(3))(2)(CH(3)OH)].4H(2)O (3) have triangulo trinuclear composition. The syntheses, X-ray structures, and spectroscopic and magnetic properties of these complexes are described. Compound 1 has a noncentrosymmetric structure with a rectangular Cu(2)(OPh)(2) core. It appears to be a rare example of a phenolato-bridged Cu(II) dimer exhibiting ferromagnetic interactions (J = 0.93 cm(-)(1)), a behavior in agreement with the theoretical predictions but seldom observed experimentally. In compounds 2 and 3, the copper centers are triangularly disposed, and the molecules have a shape much like that of a butterfly. The terminal copper centers Cu(1) and Cu(2) in 2 and 3 have distorted square pyramidal geometry, connected to each other by a bridging chloro- (in 2) or azido ligand (in 3) in "end to end" fashion. The central copper center (Cu(3) in 2 and Cu in 3) in both the compounds has distorted square planar geometry. The separations between the metal centers, viz. Cu(1)...Cu(2), Cu(2)...Cu(3), and Cu(3)...Cu(1), are 4.826, 3.214, and 3.244 A, respectively, in 2. The corresponding distances in 3 are 5.590, 3.178, and 3.485 A, respectively. The overall magnetic behaviors in 2 and 3 are consistent with antiferromagnetic interactions between the spin centers. In 3, the exchange couplings between the terminal and central copper centers J(Cu(1))(-)(Cu) and J(Cu(2))(-)(Cu) appear to be equal (-234 cm(-)(1)), resulting in an S = (1)/(2) ground state at temperatures near or below 77 K.     

Structure,spectroscopy and electronic properties of neutral lattice-like (MgO) n clusters: a study based on a blending of DFT with stochastic algorithms inspired by natural processes

In this article, we explore the feasibility of using stochastic optimization techniques, which are inspired by natural processes, namely simulated annealing (SA) and genetic algorithm (GA) in association with DFT, to find out the global minimum structures of (MgO) _n clusters with n being in the range of 2–15. To check whether the structures are indeed the correct ones, we proceed to do several property calculations like IR-spectroscopic modes, vertical excitation energy, cluster-formation energy, vertical ionization potential, the HOMO–LUMO gap as well as polarizability and hyperpolarizability—both static and dynamic. We emphasize on the point that an initial determination of structure using SA/GA leads to very quick relaxation to structures which are very close to the structures predicted from quantum chemical calculations done from the outsets like DFT. The general pattern of these systems to form beautiful three-dimensional lattice networks is also evident from our study.     

Equilibrium studies in solution involving nickel(II) complexes of flexidentate Schiff base ligands: isolation and structural characterization of the planar red and octahedral green species involved in the equilibrium

Three new flexidentate 5-substituted salicylaldimino Schiff base ligands (L1-OH-L3-OH) based on 1-(2-aminoethyl)piperazine (X=H, L1-OH; X=NO2, L2-OH; and X=Br, L3-OH) and their nickel(II) complexes (1a, 1b, 2, and 3) have been reported. The piperazinyl arm of these ligands can in principle have both boat and chair conformations that allow the ligands to bind the Ni(II) center in an ambidentate manner, forming square-planar and/or octahedral complexes. The nature of substitution in the salicylaldehyde aromatic ring and the type of associated anion in the complexes have profound influences on the coordination geometry of the isolated products. With the parent ligand L1-OH, the product obtained is either a planar red compound [Ni(L1-O)]+, isolated as tetraphenylborate salt (1a), or an octahedral green compound [Ni(L1-NH)(H2O)3](2+), isolated with sulfate anion (1b); both have been crystallographically characterized. In aqueous solution, both these planar (S=0) and octahedral (S=1) forms are in equilibrium that has been followed in the temperature range 298-338 K by 1H NMR technique using the protocol of Evans's method. The large exothermicity of the equilibrium process [Ni(L1-O)]+ + 3H2O + H+<=>[Ni(L1-NH)(H2O)3](2+) (DeltaH degrees=-46 +/- 0.2 kJ mol(-1) and DeltaS degrees=-133 +/- 5 J K(-1) mol(-1)) reflects formation of three new Ni-OH2 bonds in going from planar to the octahedral species. With the 5-nitro derivative ligand L2-OH, the sole product is an octahedral compound 2, isolated as a sulfate salt while with the bromo derivative ligand L3-OH, the exclusive product is a planar molecule 3 with associated tetraphenylborate anion. Both 2 and 3 have been structurally characterized by X-ray diffraction analysis.     

Adduct formation between alkali metal ions and anionic LV(V)O(2)(-) (L(2-) = tridentate ONS ligands) species: syntheses, structural investigation, and photochemical studies

Syntheses of alkali metal adducts [LVO(2)M(H(2)O)(n)] (1-7) (M = Na(+), K(+), Rb(+), and Cs(+); L = L(1)(-)L(3)) of anionic cis-dioxovanadium(V) species (LVO(2)(-)) of tridentate dithiocarbazate-based Schiff base ligands H(2)L (S-methyl-3-((5-(R-2-hydroxyphenyl))methyl)dithiocarbazate, R = H, L = L(1); R = NO(2), L = L(2); R = Br, L = L(3)) have been reported. The LVO(2)(-) moieties here behave like an analogue of carboxylate group and have displayed interesting variations in their binding pattern with the change in size of the alkali metal ions as revealed in the solid state from the X-ray crystallographic analysis of 1, 3, 6, and 7. The compounds have extended chain structures, forming ion channels, and are stabilized by strong Coulombic and hydrogen-bonded interactions. The number of coordinated water molecules in [LVO(2)M(H(2)O)(n)] decreases as the charge density on the alkali metal ion decreases (n = 3.5 for Na(+) and 1 for K(+) and Rb(+), while, for Cs(+), no coordinated water molecule is present). In solution, compounds 1-7 are stable in water and methanol, while in aprotic solvents of higher donor strengths, viz. CH(3)CN, DMF and DMSO, they undergo photoinduced reduction when exposed to visible light, yielding green solutions from their initial yellow color. The putative product is a mixed-oxidation (mu-oxo)divanadium(IV/V) species as revealed from EPR, electronic spectroscopy, dynamic (1)H NMR, and redox studies.