A Preparative Synthesis of 1-Amino-3-hydroxypropylphosphonic Acid (Phosphonic Analogue of Homoserine)

A novel procedure for the preparation of the phosphonic analogue of homoserine is described starting from the commercially available 4-acetoxy-azetidin-2-one.     

Automated self-organising vehicles for Barclays Cycle Hire

Self-organisation is a distributed and asynchronous process in which global pattern or behaviour emerge from local components of the system. Neither central control nor external intervention is necessary during this process. Self-organising systems are adaptive and robust, which are appealing properties from a design and engineering point of view. In this paper, we present an innovative self-organisation approach for a dynamic vehicle routing problem, the Barclay Cycle Hire truck dispatch. In addition, we introduce an evolutionary algorithm capable of automatically configuring the “self-organising trucks”. Experimental results show the evolutionary algorithm improves the overall fitness of the self-organising trucks; and we observe global emergent behaviour in the way trucks self-organise.     

Receptor-based computational screening of compound databases: the main docking-scoring engines

The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance with many new and exciting techniques. The number of protein structures and/or chemical ligands is constantly growing, through the use of parallel chemistry, X-ray crystallography, NMR or homology modeling methods and so is the theoretical understanding of protein-ligand interactions. As such, structure-based approaches to drug-design and in silico screening are becoming routine part of most modern lead discovery programs. Prioritization of compound libraries is an extremely important task that aims at the rapid identification of tight-binding ligands and ultimately new therapeutic compounds. These in silico approaches combined with other experimental methods facilitate the design of new medicines to treat cardiovascular, degenerative, infectious, and neoplastic diseases, among others. Here, we review key concepts and specific features of several selected ligand-receptor docking/scoring methods while several other topics pertaining to the field of in silico screening are reviewed in the following articles of this special issue of Current Protein and Peptide Science.     

低配位有机磷化学研究概况

长期以来,有机磷化学研究的核心内容主要集中在σ3和σ4的有机磷化合物及其衍生物方面,而低配位的有机磷化合物的研究则远远落后.本文简要综述了目前低配位的有机磷化合物σ1,λ1-亚膦烯、σ1,λ3-膦炔、σ2,λ3-膦烯和σ2,λ3-膦杂苯研究的最新进展,包括它们的合成及其在均相催化和材料等方面的应用.     

The radical trap in atom transfer radical polymerization need not be thermodynamically stable. A study of the MoX(3)(PMe(3))(3) catalysts

The molybdenum(III) coordination complexes MoX(3)(PMe(3))(3) (X = Cl, Br, and I) are capable of controlling styrene polymerization under typical atom transfer radical polymerization (ATRP) conditions, in conjunction with 2-bromoethylbenzene (BEB) as an initiator. The process is accelerated by the presence of Al(OPr(i))(3) as a cocatalyst. Electrochemical and synthetic studies aimed at identifying the nature of the spin trap have been carried out. The cyclic voltammogram of MoX(3)(PMe(3))(3) (X = Cl, Br, I) shows partial reversibility (increasing in the order Cl < Br < I) for the one-electron oxidation wave. Addition of X(-) changes the voltammogram, indicating the formation of MoX(4)(PMe(3))(3) for X = Cl and Br. On the other hand, I(-) is more easily oxidized than the MoI(3)(PMe(3))(3) complex; thus, the putative MoI(4)(PMe(3))(3) complex is redox unstable. Electrochemical studies of MoI(3)(PMe(3))(3) in the presence of X(-) (X = Cl or Br) reveal the occurrence of facile halide-exchange processes, leading to the conclusion that the MoI(3)X(PMe(3))(3) products are also redox unstable. The oxidation of MoX(3)(PMe(3))(3) with (1)/(2)Br(2) yields MoX(3)Br(PMe(3))(3) (X = Cl, Br), whose molecular nature is confirmed by single-crystal X-ray analyses. On the other hand, the oxidation of MoI(3)(PMe(3))(3) by I(2) slowly yields a tetraiodomolybdate(III) salt of iodotrimethylphosphonium, [Me(3)PI][MoI(4)(PMe(3))(3)], as confirmed by an X-ray study. This product has no controlling ability in radical polymerization. The redox instability of MoI(3)X(PMe(3))(3) can be reconciled with its involvement as a radical trapping species in the MoI(3)(PMe(3))(3)-catalyzed ATRP, given the second-order nature of its decomposition rate.     

Lutetium bis(tetra-tert-butylphthalocyaninato): a superior redox probe to study the transfer of anions and cations across the water/nitrobenzene interface by means of square-wave voltammetry at the three-phase electrode

The redox properties of lutetium bis(tetra-tert-butylphthalocyaninato) (LBPC) have been studied in nitrobenzene that is deposited as a microfilm on the surface of highly oriented pyrolytic graphite electrodes. The behavior of the modified electrode, which is immersed in an aqueous electrolyte solution, is typical for the three-phase electrode (Scholz, F.; Komorsky-Lovri?, S.; Lovri?, M. Electrochem. Comm. 2000, 2, 112-118). LBPC can be both oxidized and reduced in one electron reversible processes. The oxidation and the reduction of LBPC at the graphite/nitrobenzene interface is accompanied by the transfer of anion or cation, respectively, from the aqueous phase into the organic layer. Thus, using LBPC as a redox probe for the three-phase electrode, the transfer of both anions and cations across the water/nitrobenzene interface can be studied in a single experiment. The hydrophobicity of LBPC is so high that it enables inspection of cations and anions with Delta (nb)(w) (G)(theta)(Cat+) < or = 43 kJ/mol and Delta (nb)(w) (G)(theta)(X-) < or = 50 kJ/mol, respectively. The direct transfer of Na(+) and Li(+) from water to nitrobenzene, mutually saturated, is achieved for the first time at a macroscopic water/nitrobenzene interface.     

Norbornane: an investigation into its valence electronic structure using electron momentum spectroscopy, and density functional and Green's function theories

We report on the results of an exhaustive study of the valence electronic structure of norbornane (C(7)H(12)), up to binding energies of 29 eV. Experimental electron momentum spectroscopy and theoretical Green's function and density functional theory approaches were all utilized in this investigation. A stringent comparison between the electron momentum spectroscopy and theoretical orbital momentum distributions found that, among all the tested models, the combination of the Becke-Perdew functional and a polarized valence basis set of triple-zeta quality provides the best representation of the electron momentum distributions for all of the 20 valence orbitals of norbornane. This experimentally validated quantum chemistry model was then used to extract some chemically important properties of norbornane. When these calculated properties are compared to corresponding results from other independent measurements, generally good agreement is found. Green's function calculations with the aid of the third-order algebraic diagrammatic construction scheme indicate that the orbital picture of ionization breaks down at binding energies larger than 22.5 eV. Despite this complication, they enable insights within 0.2 eV accuracy into the available ultraviolet photoemission and newly presented (e,2e) ionization spectra, except for the band associated with the 1a(2) (-1) one-hole state, which is probably subject to rather significant vibronic coupling effects, and a band at approximately 25 eV characterized by a momentum distribution of "s-type" symmetry, which Green's function calculations fail to reproduce. We note the vicinity of the vertical double ionization threshold at approximately 26 eV.     

Controlled radical polymerization of alkyl acrylates and styrene using a half-sandwich molybdenum(III) complex containing diazadiene ligands

The half-sandwich molybdenum(III) complex CpMoCl₂(ⁱPr₂-dad) (ⁱPr₂-dad=ⁱPr-NCH-CHN-ⁱPr) proved to be an effective metal catalyst for the controlled radical polymerization of methyl acrylate, butyl acrylate, and styrene. In conjunction with an alkyl iodide [R-I: CH₃CH(COOEt)I] as an initiator and in the presence or absence of Al(O-i-Pr)₃ as a co-catalyst, the molybdenum-based system gave polymers with narrow molecular weight distributions. The in situ addition of styrene to a macroinitiator of poly(methylacrylate) afforded an AB-type block copolymer.     

An experimental and computational study on the effect of Al(OiPr)3 on atom-transfer radical polymerization and on the catalyst-dormant-chain halogen exchange

Compound Al(OiPr)3 is shown to catalyze the halide-exchange process leading from [Mo(Cp)Cl2(iPrN=CH-CH=NiPr)] and CH3CH(X)COOEt (X=Br, I) to the mixed-halide complexes [Mo(Cp)ClX(iPrN=CH-CH=NiPr)]. On the other hand, no significant acceleration is observed for the related exchange between [MoX3(PMe3)3] (X=Cl, I) and PhCH(Br)CH3, by analogy to a previous report dealing with the Ru(II) complex [RuCl2(PPh3)3]. A DFT computation study, carried out on the model complexes [Mo(Cp)Cl2(PH3)2], [MoCl3(PH3)3], and [RuCl2(PH3)3], and on the model initiators CH3CH(Cl)COOCH3, CH3Cl, and CH3Br, reveals that the 16-electron Ru(II) complex is able to coordinate the organic halide RX in a slightly exothermic process to yield saturated, diamagnetic [RuCl2(PH3)3(RX)] adducts. The 15-electron [MoCl3(PH3)3] complex is equally capable of forming an adduct, that is, the 17-electron [MoCl3(PH3)3(CH3Cl)] complex with a spin doublet configuration, although the process is endothermic, because it requires an energetically costly electron-pairing process. The interaction between the 17-electron [Mo(Cp)Cl2(PH3)2] complex and CH3Cl, on the other hand, is repulsive and does not lead to a stable 19-electron adduct. The [RuCl2(PH3)3(CH3X)] system leads to an isomeric complex [RuClX(PH3)3(CH3Cl)] by internal nucleophilic substitution at the carbon atom. The transition state of this process for X=Cl (degenerate exchange) is located at lower energy than the transition state required for halogen-atom transfer leading to [RuCl3(PH3)3] and the free radical CH3. On the basis of these results, the uncatalyzed halide exchange is interpreted as the result of a competitive S(N)i process, whose feasibility depends on the electronic configuration of the transition-metal complex. The catalytic action of Al(OiPr)3 on atom-transfer radical polymerization (and on halide exchange for the 17-electron half-sandwich Mo(III) complex) results from a more favorable Lewis acid-base interaction with the oxidized metal complex, in which the transferred halogen atom is bound to a more electropositive element. This conclusion derives from DFT studies of the model [Al(OCH3)3]n (n=1,2,3,4) compounds, and on the interaction of Al(OCH3)3 with CH3Cl and with the [Mo(Cp)Cl3(PH3)2] and [RuCl3(PH3)3] complexes.     

Temporally and spatially heterogeneous distribution of mTHPC in a murine tumor observed by two-color confocal fluorescence imaging and spectroscopy in a whole-mount model

Efficient intratumor delivery of anticancer drugs and photosensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole-mount two-color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 mum diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.