X-ray Structures of Three Penem Antibiotics: Molecular Mechanical and Dynamic Aspects

The structures of three -lactam penem antibiotics—i.e. the sodium[5R-[5,6(R*)]]-6-(1-hydroxyethyl)-7-oxo-3-[[(1-pyrrolidinylthioxomethyl)thio]methyl]-4-thia-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylate (compound 1), the [5R-[3(S*),5,6(R*)]]-3-[[2-(aminocarbonyl)-1-pyrrolidinyl] methyl]-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (compound 2), and the [5R-[5,6(R*)]]-3-[[(2-amino-2-oxoethyl) methylamino]methyl]-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (compound 3)—have been determined by X-ray analyses. In the crystal lattice two conformational isomers of 1 are present, which differ from each other in the spatial arrangement of the dithiocarbamate chain. Compounds 2 and 3 are in zwitterionic form, being the hydrogen of the carboxylic acid moved to the amino nitrogen of the chain at C2. This hydrogen atom, in both molecules, forms intramolecular hydrogen bonds with an oxygen atom of the carboxylate moiety and with the oxygen atom of the amido group of the side chain. The 3D structures of 1, 2, and 3 have been compared with those of previously reported -lactam penem antibiotics. Particularly, the Woodward parameter and the Cohen distance, which are considered important in determining the antibiotic activity, have been discussed. Least-squares minimizations (RMS) of the distances between nuclei of selected pairs of atoms defining the pharmacological pattern have been performed, comparing five common antibiotics (imipenem, ritipenem, cephaloridine, amoxycillin, and benzylpenicillin) with our compounds. Finally, molecular dynamics calculations have been carried out on the three penem antibiotics at different temperatures. The conformational behavior of the hydroxyethyl chain, the carboxylate group, and the chain at C2 is discussed by considering the variation of some selected dihedral angles.     

On the Swendsen-Wang dynamics. II. Critical droplets and homogeneous nucleation at low temperature for the two-dimensional Ising model

We consider the Swendsen-Wang dynamics for the two-dimensional Ising model at low temperature in the presence of a small negative magnetic fieldh and with plus boundary conditions at the boundary of an arbitrarily large square. We analyze in detail the tunneling from the metastable phase to the stable one. In particular, we obtain an upper bound on the tunneling timet by explicitly constructing paths in the space of spin configurations that drive the system from the metastable phase to the stable one. In our analysis the transition takes place through the formation of droplets of the right phase inside the wrong one with side greater than a certain critical valuel _c . The values of the tunneling time and ofl _c coincide with those found for a single-spin-flip dynamics in finite volume by Jordao-Neves and Schonmann.     

Group motions in the glassy state of some substituted polystyrenes and poly(vinyl benzoates)

Mechanical damping measurements were carried out in the range of 10³–10⁵ cps and between 60°K. and the softening point on some substituted Polystyrenes and poly(vinyl benzoates) containing different substituents (methyl groups, methoxy groups, and halogen atoms) either in the ring or in the main chain. The ortho and meta ring-substituted polystyrenes do not show any secondary mechanical relaxation in the glassy state, although all the other substituted polystyrenes, exhibit a low-temperature damping peak (δ process) (which is in some way connected with ring motions) whose height and temperature location depend on nature, position, and number of substituents. Substituents in the para position of the ring or in the α position in the backbone chain shift the δ peak of the unsubstituted polystyrene towards higher temperatures; this shift is accompanied by an increase of the apparent activation energy E^*. Substitution in the β position, on the contrary, does not affect the δ peak. Analogous results are obtained for substituted poly(vinyl benzoates), which exhibit, in addition, a β relaxation effect, associated with carboxyl group motions. A very good correlation is found between the values of E* and the limiting relaxation time τ for the δ relaxation of polystyrenes and poly(vinyl benzoates), similarly substituted in the ring, indicating that the δ relaxation leads to absorption curves in the mechanical relaxation spectrum which are characteristic of the structure of the aromatic side chain.     

A multinuclear NMR relaxometry study of ternary adducts formed between heptadentate Gd(III) chelates and L-lactate

Dramatic relaxation enhancements of L-lactate resonances have been observed upon formation of ternary adducts with Gd(III) complexes of heptadentate DO3A and DO3A-like ligands (DO3A = 1,4,7,10-tetraazaciclododecane-1,4,7-triacetic acid). Detailed 1H and 17O NMR relaxometry investigations allow us to obtain structural, dynamic and thermodynamic information on the ternary complexes in which L-lactate acts as a bidentate ligand replacing two water molecules in the inner coordination sphere of the Gd(III) ion. It has been found that the exchange rate of the coordinated L-lactate is modulated by the structural and electronic properties of the parent Gd-heptacoordinated macrocyclic chelate. In addition to the characterisation of the relaxation behaviour of the 1H methyl resonance of L-lactate, this study has been extended to its 13C isomer (fully enriched at the three positions) and to the trifluoro-L-lactate. The obtained results may be relevant to the development of relaxation agents able to promote the relaxation enhancement of specific substrates detectable by in vivo magnetic resonance spectroscopy.     

Renormalization group at criticality and complete analyticity of constrained models: A numerical study

We study the majority rule transformation applied to the Gibbs measure for the 2D Ising model at the critical point. The aim is to show that the renormalized Hamiltonian is well defined in the sense that the renormalized measure is Gibbsian. We analyze the validity of Dobrushin-Shlosman uniqueness (DSU) finite-size condition for the constrained models corresponding to different configurations of the image system. It is known that DSU implies, in our 2D case, complete analyticity from which, as recently shown by Haller and Kennedy. Gibbsianness follows. We introduce a Monte Carlo algorithm to compute an upper bound to Vasserstein distance (appearing in DSU) between finite-volume Gibbs measures with different boundary conditions. We get strong numerical evidence that indeed the DSU condition is verified for a large enough volumeV for all constrained models.     

Metastability and nucleation for the Blume-Capel model. Different mechanisms of transition

We study metastability and nucleation for the Blume-Capel model: a ferromagnetic nearest neighbor two-dimensional lattice system with spin variables taking values in {–1,0, +1}. We consider large but finite volume, small fixed magnetic fieldh, and chemical potential in the limit of zero temperature; we analyze the first excursion from the metastable –1 configuration to the stable +1 configuration. We compute the asymptotic behavior of the transition time and describe the typical tube of trajectories during the transition. We show that, unexpectedly, the mechanism of transition changes abruptly when the lineh=2 is crossed.     

Superconductor-insulator transition of Josephson-junction arrays on a honeycomb lattice in a magnetic field

We study the superconductor to insulator transition at zero temperature in aJosephson-junction array model on a honeycomb lattice with f flux quantum perplaquette. The path integral representation of the model corresponds to a (2 + 1)-dimensional classical model, which isused to investigate the critical behavior by extensive Monte Carlo simulations on largesystem sizes. In contrast to the model on a square lattice, the transition is found to befirst order for f = 1 /3 and continuous for f = 1 / 2 but in a different universality class.The correlation-length critical exponent is estimated from finite-size scaling of vortexcorrelations. The estimated universal conductivity at the transition is approximately fourtimes its value for f =0. The results are compared with experimental observations on ultrathinsuperconducting films with a triangular lattice of nanoholes in a transverse magneticfield.     

On Sojourn Distributions of Processes Related to Some Higher-Order Heat-Type Equations

It is well known that the sojourn time of Brownian motion B(t), t>0 on the positive half-line, during the interval [0, t] and under the condition B(t)=0, is uniformly distributed, while it has the form of the corrected arc-sine law when the condition B(t)>0 is assumed. We find the analogues of these laws for processes X(t), t>0 governed by signed measures whose densities are the fundamental solutions of third and fourth-order heat-type equations. Surprisingly, both laws hold for the fourth-order process. The uniform law is still valid for the third-order process but a different law emerges when the condition X(t)>0 is considered.     

Lanthanide-loaded paramagnetic liposomes as switchable magnetically oriented nanovesicles

Osmotically shrunken liposomes loaded with paramagnetic lanthanide(III) complexes orient in a static magnetic field according to the sign of their magnetic susceptibility anisotropy (Deltachi). The magnitude and sign of Deltachi are modulated by the magnetic properties of the Ln (III) ion, by the structural characteristics of the metal chelate, and by the stereochemical arrangement of the lipophilic substituents.     

Organogermanium polymers prepared from s‐indacene and carbodiimide compounds

The synthesis of bis‐organogermanium compounds including s‐indacene structure was described and showed the formation of one type of trans isomer characterized by spectroscopic methods. In the same way, the digermyl‐s‐indacene dichlorides were prepared and structural characterizations confirmed the unique formation of trans isomers. These digermyl‐s‐indacene dichlorides were used as monomers in a polymerization reaction in order to prepare poly(germyl‐s‐indacenes) and poly(germyl‐s‐indacene carbodiimides). However, only the products obtained from tetraalkyl‐s‐indacene reached high molecular weight, probably due to a minor steric hindrance compared to the hexaalkyl‐s‐indacene. Thermal degradation only starts from 250°C for poly(germyl‐s‐indacene carbodiimides) and from 350°C for poly(germyl‐s‐indacenes). The structures of the first digermyl‐s‐indacene dichlorides were determined by X‐ray analysis, confirming that the chlorogermyl groups are located in trans positions. Copyright © 2012 John Wiley & Sons, Ltd.