Modulation of the pK(a) of metal-bound water via oxidation of thiolato sulfur in model complexes of Co(III) containing nitrile hydratase: insight into possible effect of cysteine oxidation in Co-nitrile hydratase

The Co(III) complexes of N,N'-bis(2-mercaptophenyl)pyridine-2,6-dicarboxamide (PyPSH(4)), a designed pentadentate ligand with built-in carboxamide and thiolate groups, have been synthesized and studied to gain insight into the role of Cys-S oxidation in Co-containing nitrile hydratase (Co-NHase). Reaction of [Co(NH(3))(5)Cl]Cl(2) with PyPS(4)(-) in DMF affords the thiolato-bridged dimeric Co(III) complex (Et(4)N)(2)[Co(2)(PyPS)(2)] (1). Although the bridged structure is quite robust, reaction of (Et(4)N)(CN) with 1 in acetonitrile affords the monomeric species (Et(4)N)(2)[Co(PyPS)(CN)] (2). Oxidation of 2 with H(2)O(2) in acetonitrile gives rise to a mixture which, upon chromatographic purification, yields K(2)[Co(PyPSO(2)(OSO(2))(CN] (3), a species containing asymmetrically oxidized thiolates. The Co(III) metal center in 3 is coordinated to a S-bound sulfinate and an O-bound sulfonate (OSO(2)) group. Upon oxidation with H(2)O(2), 1 affords an asymmetrically oxidized dimer (Et(4)N)(2)[Co(2)(PyPS(SO(2)))(2)] (4) in which only the terminal thiolates are oxidized to form S-bound sulfinate groups while the bridging thiolates remain unchanged. The thiolato-bridge in 4 is also cleaved upon reaction with (Et(4)N)(CN) in acetonitrile, and one obtains (Et(4)N)(2)[Co(PyPS(SO(2)))(CN)] (5), a species that contains both coordinated thiolate and S-bound sulfinate around Co(III). The structures of 1-4 have been determined. The spectroscopic properties and reactivity of all the complexes have been studied to understand the behavior of the Co(III) site in Co-NHase. Unlike typical Co(III) complexes with bound CN(-) ligands, the Co(III) centers in 2 and 5 are labile and rapidly lose CN(-) in aqueous solutions. Since 3 does not show this lability, it appears that at least one thiolato sulfur donor is required in the first coordination sphere for the Co(III) center in such species to exhibit lability. Both 2 and 5 are converted to the aqua complexes [Co(PyPS)(H(2)O)](-) and [Co(PyPS(SO(2))(H(2)O)](-) in aqueous solutions. The pK(a) values of the bound water in these two species, determined by spectrophotometry, are 8.3 +/- 0.03 and 7.2 +/- 0.06, respectively. Oxidation of the thiolato sulfur (to sulfinate) therefore increases the acidity of the bound water. Since 2 and 5 promote hydrolysis of acetonitrile at pH values above their corresponding pK(a) values, it is also evident that a metal-bound hydroxide is a key player in the mechanism of hydrolysis by these model complexes of Co-NHase. The required presence of a Cys-sulfinic residue and one water molecule at the Co(III) site of Co-NHase as well as the optimal pH of the enzyme near 7 suggests that (i) modulation of the pK(a) of the bound water molecule at the active site of the enzyme could be one role of the oxidized Cys-S residue(s) and (ii) a cobalt-bound hydroxide could be responsible for the hydrolysis of nitriles by Co-NHase.     

Microscopic approach to the pseudo-spin-1/2 Hamiltonian for Kramers doublets in exchange coupled Co(II) pairs

The microscopic theory of the magnetically anisotropic effective pseudo-spin-(1)/(2) Hamiltonian for a pair of Co(2+) ions is reported. In the framework of the second-order perturbation approach, the analytical expressions are found for the components of the tensor of the exchange interaction, g-tensor, and the factor in the temperature independent paramagnetic contribution. The parameters of the Hamiltonian are expressed in terms of the basic intra- and intercenter parameters of the pair, namely, the spin-orbit coupling constant, orbital reduction factor, exchange integral, and low symmetry crystal field parameters including axial and rhombic terms.     

A novel organic-inorganic hybrid based on a dinuclear copper complex supported on a keggin polyoxometalate

The autoassembly process of copper-oxalate dimers and Keggin type polyoxometalates leads to the first example of a new family of organic-inorganic hybrids, K(14)[(Cu(2)(bpy)(2)(mu-ox))(SiW(11)O(39)Cu(H(2)O))](2)[SiW(11)O(39)Cu(H(2)O)]. approximately 55H(2)O. This compound crystallizes in the monoclinic space group C2/m, a = 37.932(6) A, b = 21.303(3) A, c = 12.546(2) A, beta = 106.16(1) degrees, Z = 2. The crystal structure reveals the presence of a polymeric hybrid built up of alternating dimer and polyoxometalate entities.     

Conformational preferences driven by the C-methyl substituent in chelated o-diphenylphosphino-alpha-methyl-N,N-dimethylbenzylamine rhodium complexes

The stereochemistry of the chelate rings of a number of rhodium aminophosphine complexes is studied by NMR spectroscopy. The similarity in the variable-temperature behavior for the different compounds is consistent with them having in common highly preferred chelate ring conformations. The six-membered metallacycle of coordinated (R)-PN (PN = o-diphenylphosphino-alpha-methyl-N,N-dimethylbenzylamine) adopts a delta conformation in the solid state. NMR experiments indicate that this conformation is strongly favored in solution as well. The preferred sense of helicity is imposed by the absolute configuration of the stereogenic carbon atom on the ligand, which exerts an important steric control. The complex [Rh(TFB)((C(6)H(4)CHMeNMe(2))(2)P(C(6)H(4)CHMeNHMe(2)))](BF(4))(2).H(2)O.Me(2)CO crystallizes in the monoclinic space group P2(1) with a = 12.0548(11) A, b = 16.139(2) A, c = 12.1804(10) A, beta = 100.742(9) degrees, Z = 4.     

Dioxygen activation by an osmium-dihydride: preparation and characterization of a d4 square-planar complex

Exposure of OsH2Cl2(PiPr3)2 to air or bubbling with pure O2 affords the dioxo-Os(VI) compound OsO2Cl2(PiPr3)2 as result of a direct O=O double bond activation reaction. This Os(VI) species is reduced in the presence of n-BuLi to the novel dioxo-Os(IV) derivative OsO2(PiPr3)2, a rare example of a d4 square-planar compound.     

Region-based wavelet coding methods for digital mammography

Spatial resolution and contrast sensitivity requirements for some types of medical image techniques, including mammography, delay the implementation of new digital technologies, namely, computer-aided diagnosis, picture archiving and communications systems, or teleradiology. In order to reduce transmission time and storage cost, an efficient data-compression scheme to reduce digital data without significant degradation of medical image quality is needed. In this study, we have applied two region-based compression methods to digital mammograms. In both methods, after segmenting the breast region, a region-based discrete wavelet transform is applied, followed by an object-based extension of the set partitioning in hierarchical trees (OB-SPIHT) coding algorithm in one method, and an object-based extension of the set partitioned embedded block (OB-SPECK) coding algorithm in the other. We have compared these specific implementations against the original SPIHT and the new standard JPEG 2000, both using reversible and irreversible filters, on five digital mammograms compressed at rates ranging from 0.1 to 1.0 bit per pixel (bbp). Distortion was evaluated for all images and compression rates by the peak signal-to-noise ratio. For all images, OB-SPIHT and OB-SPECK performed substantially better than the traditional SPIHT and JPEG 2000, and a slight difference in performance was found between them. A comparison applying SPIHT and the standard JPEG 2000 to the same set of images with the background pixels fixed to zero was also carried out, obtaining similar implementation as region-based methods. For digital mammography, region-based compression methods represent an improvement in compression efficiency from full-image methods, also providing the possibility of encoding multiple regions of interest independently.     

AC-coupled front-end for biopotential measurements

AC coupling is essential in biopotential measurements. Electrode offset potentials can be several orders of magnitude larger than the amplitudes of the biological signals of interest, thus limiting the admissible gain of a dc-coupled front end to prevent amplifier saturation. A high-gain input stage needs ac input coupling. This can be achieved by series capacitors, but in order to provide a bias path, grounded resistors are usually included, which degrade the common mode rejection ratio (CMRR). This paper proposes a novel balanced input ac-coupling network that provides a bias path without any connection to ground, thus resulting in a high CMRR. The circuit being passive, it does not limit the differential dc input voltage. Furthermore, differential signals are ac coupled, whereas common-mode voltages are dc coupled, thus allowing the closed-loop control of the dc common mode voltage by means of a driven-right-leg circuit. This makes the circuit compatible with common-mode dc shifting strategies intended for single-supply biopotential amplifiers. The proposed circuit allows the implementation of high-gain biopotential amplifiers with a reduced number of parts, thus resulting in low power consumption. An electrocardiogram amplifier built according to the proposed design achieves a CMRR of 123 dB at 50 Hz.     

Dosage individualization of erythropoietin using a profile-dependent support vector regression

The external administration of recombinant human erythropoietin is the chosen treatment for those patients with secondary anemia due to chronic renal failure in periodic hemodialysis. The objective of this paper is to carry out an individualized prediction of the EPO dosage to be administered to those patients. The high cost of this medication, its side-effects and the phenomenon of potential resistance which some individuals suffer all justify the need for a model which is capable of optimizing dosage individualization. A group of 110 patients and several patient factors were used to develop the models. The support vector regressor (SVR) is benchmarked with the classical multilayer perceptron (MLP) and the Autoregressive Conditional Heteroskedasticity (ARCH) model. We introduce a priori knowledge by relaxing or tightening the epsilon-insensitive region and the penalization parameter depending on the time period of the patients' follow-up. The so-called profile-dependent SVR (PD-SVR) improves results of the standard SVR method and the MLP. We perform sensitivity analysis on the MLP and inspect the distribution of the support vectors in the input and feature spaces in order to gain knowledge about the problem.     

Asymmetric intermolecular Pauson-Khand reactions of unstrained olefins: the (o-dimethylamino)phenylsulfinyl group as an efficient chiral auxiliary

The first asymmetric version of intermolecular Pauson-Khand reactions of unstrained alkenes is described. Generally simple acyclic alkenes exhibit low reactivity and regioselectivity in intermolecular Pauson-Khand reactions; however, o-(dimethylamino)phenyl vinyl sulfoxide reacts under very mild conditions with a wide variety of terminal alkynes in a completely regioselective and highly stereoselective manner. The utility of the resulting 5-sulfinyl-2-cyclopentenones in asymmetric synthesis is illustrated by a very short enantioselective synthesis of the antibiotic (-)-pentenomycin I.