First palladium(II) and platinum(II) complexes from employment of 2,6-diacetylpyridine dioxime: synthesis, structural and spectroscopic characterization, and biological evaluation

Employment of the monoanion of 2,6-diacetylpyridine dioxime (dapdoH(2)) as a tridentate chelate in palladium(II) and platinum(II) chemistry is reported. The syntheses, crystal structures, spectroscopic and physicochemical characterization, and biological evaluation are described of [PdCl(dapdoH)] (1) and [PtCl(dapdoH)] (2). Reaction of PdCl(2) with 2 equivs of dapdoH(2) in MeOH under reflux gave 1, whereas the same reaction with PtCl(2) in place of PdCl(2) gave 2 in comparable yields (70-80%). The divalent metal center in both compounds is coordinated by a terminal chloro group and a N,N',N"-tridentate chelating (η(3)) dapdoH(-) ligand. Thus, each metal ion is four coordinate with a distorted square planar geometry. Characterization of both complexes with (1)H and (13)C NMR and UV-vis and electrospray ionization mass spectroscopies confirmed their integrity in DMSO solutions. Interaction of the complexes with human and bovine serum albumin has been studied with fluorescence spectroscopy, revealing their affinity for these proteins with relatively high values of binding constants. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA, and the corresponding DNA binding constants have been evaluated. Cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through intercalation, which has been also shown by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have revealed the ability of the complexes to displace the DNA-bound EB, suggesting competition with EB. The combined work demonstrates the ability of pyridyl-dioxime chelates not only to lead to polynuclear 3d-metal complexes with impressive structural motifs and interesting magnetic properties but also to yield new, mononuclear 4d- and 5d-metal complexes with biological implications.     

Development of a novel high-throughput assay for the investigation of GlyT-1b neurotransmitter transporter function

The glycine transporter (GlyT-1b) is a Na(+)/Cl(-)-dependent electrogenic transporter which mediates the rapid re-uptake of glycine from the synaptic cleft. Based on its tissue distribution, GlyT-1 has been suggested to co-localise with the NMDA receptor where it may modulate the concentration of glycine at its co-agonist binding site. This data has led to GlyT-1 inhibitors being proposed as targets for disorders such as schizophrenia and cognitive dysfunction. Radiolabelled uptake assays (e.g. [(3)H]glycine) have been traditionally used in compound screening to identify glycine transporter inhibitors. While such an assay format is useful for testing limited numbers of compounds, the identification of novel glycine uptake inhibitors requires a functional assay compatible with high-throughput screening (HTS) of large compound libraries. Here, the authors present the development of a novel homogenous cell-based assay using the FLIPR membrane potential blue dye (Molecular Devices) and FLEXstation. Pharmacological data for the GlyT-1 inhibitors Org 24598 and ALX 5407 obtained using this novel electrogenic assay correlated well with the conventional [(3)H]-glycine uptake assay format. Furthermore, the assay has been successfully miniaturised using FLIPR(3) and therefore has the potential to be used for high-throughput screening.     

A method for solving the general parametric linear complementarity problem

This paper presents a solution method for the general (mixed integer) parametric linear complementarity problem pLCP(q(θ),M), where the matrix M has a general structure and integrality restriction can be enforced on the solution. Based on the equivalence between the linear complementarity problem and mixed integer feasibility problem, we propose a mixed integer programming formulation with an objective of finding the minimum 1-norm solution for the original linear complementarity problem. The parametric linear complementarity problem is then formulated as multiparametric mixed integer programming problem, which is solved using a multiparametric programming algorithm. The proposed method is illustrated through a number of examples.     

Speed-up Benders decomposition using maximum density cut (MDC) generation

The classical implementation of Benders decomposition in some cases results in low density Benders cuts. Covering Cut Bundle (CCB) generation addresses this issue with a novel way generating a bundle of cuts which could cover more decision variables of the Benders master problem than the classical Benders cut. Our motivation to improve further CCB generation led to a new cut generation strategy. This strategy is referred to as the Maximum Density Cut (MDC) generation strategy. MDC is based on the observation that in some cases CCB generation is computational expensive to cover all decision variables of the master problem than to cover part of them. Thus MDC strategy addresses this issue by generating the cut that involves the rest of the decision variables of the master problem which are not covered in the Benders cut and/or in the CCB. MDC strategy can be applied as a complimentary step to the CCB generation as well as a standalone strategy. In this work the approach is applied to two case studies: the scheduling of crude oil and the scheduling of multi-product, multi-purpose batch plants. In both cases, MDC strategy significant decreases the number of iterations of the Benders decomposition algorithm, leading to improved CPU solution times.     

Characterization of Greek Wines by Ultraviolet–Visible Absorption Spectroscopy and Statistical Multivariate Methods

Optical absorption spectroscopy has been used to study Cretan Greek wine matured for 3 months in various barrels. Vilana and Dafni white and Kotsifali and Mandilari red wines were analyzed. The total phenolic index for all varieties and color characteristics for only the red wine were determined. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) demonstrated that the absorption spectra, combined with multivariate statistical methods, may be used to identify these varieties. The results of principal component analysis were used to infer the chemical compounds responsible for the discrimination between varieties.     

Model Independent Parametric Decision Making

Accurate knowledge of the effect of parameter uncertainty on process design and operation is essential for optimal and feasible operation of a process plant. Existing approaches dealing with uncertainty in the design and process operations level assume the existence of a well defined model to represent process behavior and in almost all cases convexity of the involved equations. However, most of the realistic case studies cannot be described by well characterised models. Thus, a new approach is presented in this paper based on the idea of High Dimensional Model Reduction technique which utilize a reduced number of model runs to build an uncertainty propagation model that expresses process feasibility. Building on this idea a systematic iterative procedure is developed for design under uncertainty with a unique characteristic of providing parametric expression of the optimal objective with respect to uncertain parameters. The proposed approach treats the system as a black box since it does not rely on the nature of the mathematical model of the process, as is illustrated through a number of examples.     

The effect of high tempered firing cycle on the bioactive behavior of sol–gel derived dental porcelain modified by bioactive glass

The purpose of the present study was to investigate the influence of end-temperature over the structural properties, chemical composition and bioactivity of dental porcelain modified by bioactive glass. In particular, sol–gel derived specimens of bioactive glass dental porcelain underwent firing at two increased end-temperatures. All specimens were characterized using Scanning Electron Microscopy, Fourier Transform Infrared and Raman Spectroscopy, X-ray diffraction and N₂-porosimetry. In vitro bioactivity test was performed too. SEM analysis of both specimens revealed smooth morphology of particles, which were sintered together. Spherical and closed porei were evident. N₂- adsorption isotherms of specimens represented non nano-/meso-porous materials. FTIR and Raman spectroscopy revealed the predominance of b-wollastonite as well as the appearance of a-cristobalite. XRD confirmed the results. In vitro tests evidenced the bioactivity of the specimens regardless of temperature. However, the increased temperature caused delayed apatite precipitation. In conclusion, increased temperature favored the sintering process initiation, along with the surface crystallization, which in turn delayed bioactivity.     

A kriging based method for the solution of mixed-integer nonlinear programs containing black-box functions

In this paper a new methodology is developed for the solution of mixed-integer nonlinear programs under uncertainty whose problem formulation is complicated by both noisy variables and black-box functions representing a lack of model equations. A branch-and-bound framework is employed to handle the integer complexity whereby the solution to the relaxed nonlinear program subproblem at each node is obtained using both global and local information. Global information is obtained using kriging models which are used to identify promising neighborhoods for local search. Response surface methodology (RSM) is then employed whereby local models are sequentially optimized to refine the problem’s lower and upper bounds. This work extends the capabilities of a previously developed kriging-response surface method enabling a wider class of problems to be addressed containing integer decisions and black box models. The proposed algorithm is applied to several small process synthesis examples and its effectiveness is evaluated in terms of the number of function calls required, number of times the global optimum is attained, and computational time.