Hydrogen-bonded interpolymer complexes as materials for pharmaceutical applications

Association of poly(carboxylic acids) and non-ionic polymers in solutions via hydrogen bonding results in formation of novel polymeric materials-interpolymer complexes. These materials can potentially be used for design of novel mucoadhesive dosage forms, development of solid drug dispersions and solubilisation of poorly soluble drugs, encapsulation technologies, preparation of nanoparticles, hydrogels, in situ gelling systems and electrically erodible materials. This review is an attempt to analyse and systematise existing literature on pharmaceutical application of hydrogen-bonded interpolymer complexes. (c) 2007 Elsevier B.V All rights reserved.

Hydrogen bond-induced pair formation of glycine on the chiral Cu{531} surface

Enantio-specific interactions on intrinsically chiral or chirally modified surfaces can be identified experimentally via comparison of the adsorption geometries of similar nonchiral and chiral molecules. Information about the effects of substrate-related and in interactions on the adsorption geometry of glycine, the only natural nonchiral amino acid, is therefore important for identifying enantio-specific interactions of larger chiral amino acids. We have studied the long- and short-range adsorption geometry and bonding properties of glycine on the intrinsically chiral Cu{531} surface with low-energy electron diffraction, near-edge X-ray absorption One structure spectroscopy, X-ray photoelectron spectroscopy, and temperature-programmed desorption. For coverages between 0.15 and 0.33 ML (saturated chemisorbed layer) and temperatures between 300 and 430 K, glycine molecules adsorb in two different azimuthal orientations, which are associated with adsorption sites on the {110} and {311} microfacets of Cu{531}. Both types of adsorption sites allow a triangular footprint with surface bonds through the two oxygen atoms and the nitrogen atom. The occupation of the two adsorption sites is equal for all coverages, which can be explained by pair formation due to similar site-specific adsorption energies and the possibility of forming hydrogen bonds between molecules on adjacent {110} and {311} sites. This is not the ease for alanine and points toward higher site specificity in the case of alanine, which is eventually responsible for the enantiomeric differences observed for the alanine system.

Mechanistic insights into a gas–solid reaction in molecular crystals: the role of hydrogen bonding

Reactions in (molecular) organic crystalline solids have been shown to be important for exerting control that is unattainable over chemical transformations in solution. Such control has also been achieved for reactions within metal– organic cages. In these examples, the reactants are already in place within the crystals following the original crystal growth. The post-synthetic modification of metal–organic frameworks (MOFs and indeed reactions and catalysis within MOFs have been recently demonstrated; in these cases the reactants enter the crystals through permanent channels. Another growing area of interest within molecular solid-state chemistry is synthesis by mechanical co-grinding of solid reactants—often referred to as mechanochemistry. Finally, in a small number of reported examples, molecules also have been shown to enter nonporous crystals directly from the gas or vapor phase, but in only a few of these examples does a change in covalent bonding result, which indicates that a reaction occurs within the nonporous crystals. It is this latter type of highly uncommon reaction that is the focus of the present study.

Self-assembled healable materials through a combination of pi-pi stacking and hydrogen bonding

The discovery of polymers with stimuli responsive physical properties is a rapidly expanding area of research. At the forefront of the field are self-healing polymers, which, when fractured can regain the mechanical properties of the material either autonomically, or in response to a stimulus. It has long been known that it is possible to promote healing in conventional thermoplastics by heating the fracture zone above the Tg of the polymer under pressure. This process requires reptation and subsequent re-entanglement of macromolecules across the fracture void, which serves to bridge, and ‘heal’ the crack. The timescale for this mechanism is highly dependent on the molecular weight of the polymer being studied. This process is in contrast to that required to affect healing in supramolecular polymers such as the plasticised, hydrogen bonded elastomer reported by Leibler et al. The disparity in bond energies between the non-covalent and covalent bonds within supramolecular polymers results in fractures propagating through scission of the comparatively weak supramolecular interactions, rather than through breaking the stronger, covalent bonds. Thus, during the healing process the macromolecules surrounding the fracture site only need sufficient energy to re-engage their supramolecular interactions in order to regenerate the strength of the pristine material. Herein we describe the design, synthesis and optimization of a new class of supramolecular polymer blends that harness the reversible nature of pi-pi stacking and hydrogen bonding interactions to produce self-supporting films with facile healable characteristics.

Hydrogen bonded supramolecular elastomers : correlating hydrogen bonding strength with morphology and rheology

A series of six low molecular weight elastomers with hydrogen bonding end-groups have been designed, synthesised and studied. The poly(urethane) based elastomers all contained essentially the same hard block content (ca. 11%) and differ only in the nature of their end-groups. Solution state 1H NMR spectroscopic analysis of model compounds featuring the end-groups demonstrate that they all exhibit very low binding constants, in the range 1.4 to 45.0 M-1 in CDCl3, yet the corresponding elastomers each possess a markedly different nanoscale morphology and rheology in the bulk. We are able to correlate small variations of the binding constant of the end-groups with dramatic changes in the bulk properties of the elastomers. These results provide an important insight into the way in which weak non-covalent interactions can be utilized to afford a range of self-assembled polyurethane based materials that feature different morphologies.

The surface geometry of carbonmonoxide and hydrogen co-adsorbed on Ni 111

A combination of photoelectron spectroscopy, temperature programmed desorption and low energy electron diffraction structure determinations have been applied to study the p(2 x 2) structures of pure hydrogen and co-adsorbed hydrogen and CO on Ni {111}. In agreement with earlier work atomic hydrogen is found to adsorb on fcc and hcp sites in the pure layer with H-Ni bond lengths of 1.74Angstrom. The substrate interlayer distances, d(12) = 2.05Angstrom and d(23) = 2.06Angstrom, are expanded with respect to clean Ni {111} with buckling of 0.04Angstrom in the first layer. In the co-adsorbed phase Co occupies hcp sites and only the hydrogen atoms on fcc sites remain on the surface. d(12) is even further expanded to 2.08Angstrom with buckling in the first and second layer of 0.06 and 0.02Angstrom, respectively. The C-O, C-Ni, and H-Ni bond lengths are within the range of values also found for the pure adsorbates.

Multistep electrochemical reduction path of clusters [Os3(CO)10(α-diimine)]: comparison of electrochemical and photochemical Os-Os(α-diimine) bond cleavage

Electrochemical reduction of the triangular clusters [Os-3(CO)(10)(alpha-dimine)] (alpha-dimine = 2,2'-bipyridine (bpy), 2,2'-bipyrimidine (bpym)) and [Os-3(CO)(10)(mu-bpym) ReBr(CO)(3)] produces primarily the corresponding radical anions. Their stability is strongly determined by the pi acceptor ability of the reducible alpha-dimine ligand, which decreases in the order mu-bpym > bpym >> bpy. Along this series, increasing delocalisation of the odd electron density in the radical anion over the Os(alpha-dimine) chelate ring causes weakening of the axial (CO)(4)Os-Os(CO)(2)(alpha-dimine) bond and its facile cleavage for alpha-diimine = bpy. In contrast, the cluster radical anion is inherently stable for the bridging bpym ligand, the strongest pi-acceptor in the studied series. In the absence of the partial delocalisation of the unpaired electron over the Re( bpym) chelate bond, the Os-3-core of the radical anion remains intact only at low temperatures. Subsequent one-electron reduction of [Os-3(CO)(10)(bpym)](center dot-) at T = 223 K gives the open-triosmium core (= Os-3*) dianion, [Os-3*(CO)(10)(bpym)](2-). Its oxidation leads to the recovery of parent [Os-3(CO)(10)( bpym)]. At room temperature, [Os-3*( CO)(10)(bpym)](2-) is formed along a two-electron (ECE) reduction path. The chemical step (C) results in the formation of an open- core radical anion that is directly reducible at the cathodic potential of the parent cluster in the second electrochemical (E) step. In weakly coordinating tetrahydrofuran, [Os-3*(CO)(10)( bpym)](2-) rapidly attacks yet non- reduced parent cluster molecules, producing the relatively stable open- core dimer [Os-3*(CO)(10)(bpym)](2)(2-) featuring two open- triangle cluster moieties connected with an ( bpym) Os - Os( bpym) bond. In butyronitrile, [Os-3*( CO)(10)(bpym)](2-) is stabilised by the solvent and the dimer [Os-3*(CO)(10)(bpym)](2)(2-) is then mainly formed by reoxidation of the dianion on reverse potential scan. The more reactive cluster [Os-3(CO)(10)(bpy)] follows the same reduction path, as supported by spectroelectrochemical results and additional valuable evidence obtained from cyclic voltammetric scans. The ultimate process in the reduction mechanism is fragmentation of the cluster core triggered by the reduction of the dimer [Os-3*(CO)(10)(alpha- diimine)](2)(2-). The products formed are [Os-2(CO)(8)](2-) and {Os(CO)(2)(alpha- diimine)}(2). The latter dinuclear fragments constitute a linear polymeric chain [Os( CO)(2)(alpha-dimine)] n that is further reducible at the alpha-dimine ligands. For alpha-dimine = bpy, the charged polymer is capable of reducing carbon dioxide. The electrochemical opening of the triosmium core in the [Os-3( CO)(10)(alpha-dimine)] clusters exhibits several common features with their photochemistry. The same Os-alpha-dimine bond dissociates in both cases but the intimate mechanisms are different.

Heterosite effects in novel heteronuclear clusters [OS2Ru(CO)(11)(PPh3)] and Os2Ru(CO)(10)(2-acetylpyridine-N-isopropylimine)]

A new synthetic route towards the mixed-metal cluster [OS2Ru(CO)(12)] is described together with the syntheses of its PPh3 and iPr-AcPy (iPr-AcPy = 2-acetylpyridine-N-isopropylimine) derivatives. The molecular structures of the novel clusters [Os2Ru(CO)(11)(PPh3)] and [Os2Ru(CO)(10)(iPr-AcPy)] were determined on the basis of crystalline solid solutions of the Os2Ru and corresponding Os-3 species. The structures reveal that coordination of the Lewis bases occurs exclusively at the ruthenium site of [Os2Ru(CO)(12)], which is in agreement with density functional theory (DFT) calculations on several structural isomers of these compounds. According to the time-dependent DFT results, the lowest optically accessible excited state of [Os2Ru(CO)(10)(iPr-AcPy)] has a prevailing sigma(Ru-Os-2)pi*(iPr-AcPy) character, with a partial sigma sigma*(Ru-Os-2) contribution. In weakly coordinating 2-chlorobutane, the excited state has a lifetime tau = 10.4 +/- 1.2 ps and produces biradicals considerably faster than observed for [Os-3(CO)10(iPr-AcPy) (tau = 25.3 +/- 0.7ps)]. In coordinating acetonitrile, the excited state of [Os2Ru(CO)(10)(iPr-AcPy)] decays mono-exponentially with a lifetime tau = 2.1 +/- 0.2 ps. In contrast to [Os-3(CO)(10)(iPr-AcPy)] that forms biradicals as the main primary photoproduct even in strongly coordinating solvents, zwitterion formation from the solvated lowest excited state is observed for the heterometallic cluster. This is concluded from time-resolved absorption studies in the microsecond time domain. Due to the lower tendency of the coordinatively unsaturated Ru+(CO)(2)(iPr-AcPy-/0) moiety to bind a Lewis base, the heteronuclear biradical and zwitterionic photoproducts live significantly shorter than their triosmium counterparts. The influence of the weaker Os-2-Ru(iPr-AcPy) bond on the redox reactivity is clearly reflected in very reactive radical anions formed upon electrochemical reduction of [Os2Ru(CO)(10)(iPr-AcPy)]. The dimer [-OS(CO)(4)-Os(CO)(4)-Ru(CO)(2)(iPr-AcPy)](2)(2-) is the only IR-detectable intermediate reduction product. The dinuclear complex [Os-2(CO)(8)](2-) and insoluble [Ru(CO)(2)(iPr-AcPy)](n), are the ultimate reduction products, proving fragmentation of the OS2Ru core.

A new interpretation of the bonding properties and UV–vis spectra of [M3(CO)12] clusters (M = Ru, Os): a TD-DFT study

DFT and TD-DFT calculations (ADF program) were performed in order to analyze the electronic structure of the [M-3(CO)(12)] clusters (M = Ru, Os) and interpret their electronic spectra. The highest occupied molecular orbitals are M-M bonding (sigma) involving different M-M bonds, both for Ru and Os. They participate in low-energy excitation processes and their depopulation should weaken M-M bonds in general. While the LUMO is M-NI and M-CO anti-bonding (sigma*), the next, higher-lying empty orbitals have a main contribution from CO (pi*) and either a small (Ru) or an almost negligible one (Os) from the metal atoms. The main difference between the two clusters comes from the different nature of these low-energy unoccupied orbitals that have a larger metal contribution in the case of ruthenium. The photochemical reactivity of the two clusters is reexamined and compared to earlier interpretations.

Low-lying excited states and primary photoproducts of [Os-3(CO)(10)-(s-cis-L)] (L = cyclohexa-1,3-diene, buta-1,3-diene)] clusters studied by picosecond time-resolved UV/Vis and IR spectroscopy and by density functional theory

Combined picosecond transient absorption and time-resolved infrared studies were performed, aimed at characterising low-lying excited states of the cluster [Os-3(CO)(10)(s-cis-L)] (L= cyclohexa-1,3-diene, 1) and monitoring the formation of its photoproducts. Theoretical (DFT and TD-DFT) calculations on the closely related cluster with L=buta-1,3-diene (2') have revealed that the low-lying electronic transitions of these [Os-3(CO)(10)(s-cis-1,3-diene)] clusters have a predominant sigma(core)pi*(CO) character. From the lowest sigmapi* excited state, cluster 1 undergoes fast Os-Os(1,3-diene) bond cleavage (tau=3.3 ps) resulting in the formation of a coordinatively unsaturated primary photoproduct (1a) with a single CO bridge. A new insight into the structure of the transient has been obtained by DFT calculations. The cleaved Os-Os(1,3-diene) bond is bridged by the donor 1,3-diene ligand, compensating for the electron deficiency at the neighbouring Os centre. Because of the unequal distribution of the electron density in transient la, a second CO bridge is formed in 20 ps in the photoproduct [Os-3(CO)(8)(mu-CO)(2)- (cyclohexa-1,3-diene)] (1b). The latter compound, absorbing strongly around 630 nm, mainly regenerates the parent cluster with a lifetime of about 100 ns in hexane. Its structure, as suggested by the DFT calculations, again contains the 1,3-diene ligand coordinated in a bridging fashion. Photoproduct 1b can therefore be assigned as a high-energy coordination isomer of the parent cluster with all Os-Os bonds bridged.

Marked influence of the bridging carbonyl ligands on the photo- and electrochemistry of the clusters [Ru-3(CO)(8)(mu-CO)(2)-(alpha-diimine)] (alpha-diimine = 2,2 '-bipyridine, 4,4 '-dimethyl-2,2 '-bipyridine and 2,2 '-bipyrimidine)

Bonding, photochemical and electrochemical properties of the clusters [Ru-3(CO)(8)(mu-CO)(2)(alpha-diimine)] (alpha-diimine=2,2'-bipyridine (1), 4,4'-dimethyl-2,2'-bipyridine (2) and 2,2'-bipyrimidine (3)) are strongly influenced by the presence of bridging carbonyl ligands. Irradiation at 471 nm initially results in the population of a sigma(Ru-3)pi*(alpha-diimine) excited state. From this state, fast decay takes place to the optically hardly directly accessible pi(Ru/mu-CO) pi*(alpha-diimine) lowest excited state. These assignments agree with theoretical (TD-DFT) results, resonance Raman and picosecond time-resolved infrared spectra. The involvement of the bridging carbonyl ligands in the electron transfer increases the energetic barrier for the formation of open-structure photoproducts such as biradicals and zwitterions. Zwitterions were therefore only obtained in strongly coordinating media such as pyridine at 250 K. The bridging carbonyl ligands also stabilize the radical anions produced upon one-electron reduction of the clusters [Ru-3(CO)(8)(mu-CO)(2)(alpha-diimine)] and observed with cyclic voltammetry, EPR and IR spectroelectrochemistry (for alpha-diimine=2,2'-bipyrimidine). In contrast, open-triangle intermediates formed along the reduction path to [Ru(CO)(2)(alpha-diimine)](n) and [Ru-2(CO)(8)](2-) are more reactive than their triosmium analogues.

Handling single node failures using agents in computer clusters

The work reported in this paper is motivated towards handling single node failures for parallel summation algorithms in computer clusters. An agent based approach is proposed in which a task to be executed is decomposed to sub-tasks and mapped onto agents that traverse computing nodes. The agents intercommunicate across computing nodes to share information during the event of a predicted node failure. Two single node failure scenarios are considered. The Message Passing Interface is employed for implementing the proposed approach. Quantitative results obtained from experiments reveal that the agent based approach can handle failures more efficiently than traditional failure handling approaches.

An MPI-based implementation of intelligent agents on clusters

Recent research in multi-agent systems incorporate fault tolerance concepts, but does not explore the extension and implementation of such ideas for large scale parallel computing systems. The work reported in this paper investigates a swarm array computing approach, namely 'Intelligent Agents'. A task to be executed on a parallel computing system is decomposed to sub-tasks and mapped onto agents that traverse an abstracted hardware layer. The agents intercommunicate across processors to share information during the event of a predicted core/processor failure and for successfully completing the task. The feasibility of the approach is validated by implementation of a parallel reduction algorithm on a computer cluster using the Message Passing Interface.

Conserved hydrophobic clusters on the surface of the Caf1A usher C-terminal domain are important for F1 antigen assembly

The outer membrane usher protein Caf1A of the plague pathogen Yersinia pestis is responsible for the assembly of a major surface antigen, the F1 capsule. The F1 capsule is mainly formed by thin linear polymers of Caf1 (capsular antigen fraction 1) protein subunits. The Caf1A usher promotes polymerization of subunits and secretion of growing polymers to the cell surface. The usher monomer (811 aa, 90.5 kDa) consists of a large transmembrane β-barrel that forms a secretion channel and three soluble domains. The periplasmic N-terminal domain binds chaperone-subunit complexes supplying new subunits for the growing fiber. The middle domain, which is structurally similar to Caf1 and other fimbrial subunits, serves as a plug that regulates the permeability of the usher. Here we describe the identification, characterization, and crystal structure of the Caf1A usher C-terminal domain (Caf1A(C)). Caf1A(C) is shown to be a periplasmic domain with a seven-stranded β-barrel fold. Analysis of C-terminal truncation mutants of Caf1A demonstrated that the presence of Caf1A(C) is crucial for the function of the usher in vivo, but that it is not required for the initial binding of chaperone-subunit complexes to the usher. Two clusters of conserved hydrophobic residues on the surface of Caf1A(C) were found to be essential for the efficient assembly of surface polymers. These clusters are conserved between the FGL family and the FGS family of chaperone-usher systems.

Hydrogen-bond assisted stabilization of the less favored conformation of a tridentate Schiff base ligand in dinuclear nickel(II) complex: an experimental and theoretical study

The Schiff base ligand, HL (2-[1-(3-methylamino-propylimino)-ethyl]-phenol), the 1:1 condensation product of 2-hydroxy acetophenone and N-methyl-1,3-diaminopropane, has been synthesized and characterized by X-ray crystallography as the perchlorate salt [H2L]ClO4 (1). The structure consists of discrete [H2L](+) cations and perchlorate anions. Two dinuclear Ni-II complexes, [Ni2L2(NO2)(2)] (2), [Ni2L2(NO3)(2)] (3) have been synthesized using this ligand and characterized by single crystal X-ray analyses. Complexes 2 and 3 are centrosymmetric dimers in which the Ni-II ions are in distorted fac- and mer-octahedral environments, respectively, bridged by two mu(2)-phenolate ions of deprotonated ligand, L. The plane of the phenyl rings and the Ni2O2 basal plane are nearly coplanar in 2 but almost perpendicular in 3. We have studied and explained this different behavior using high level DFT calculations (RI-BP86/def2-TZVP level of theory). The conformation observed in 3, which is energetically less favorable, is stabilized via intermolecular non-covalent interactions. Under the excitation of ultraviolet light, characteristic fluorescence of compound 1 was observed; by comparison fluorescence intensity decreases in case of compound 3 and completely quenched in compound 2.