(Benzo[4, 5]cyclohepta[l, 2-b]thiophen-4-ylidene)acetic Acids: Novel Non-ulcerogenic Antiinflammatory Agents

Compound (Z)- 8a has been found to display interesting antiinflammatory activity. In order to prepare derivatives with a wide variety of substituents in the aromatic part of the molecule, a new synthesis of the key intermediates 9a-g was developed starting from thiophene-3-carboxylic acid ( 11 ) and substituted benzyl bromides. The conversion of 9a-g to 10a-g follows a known procedure. Ketones 10a-g , on reaction with alkyl (dialkoxy-phosphoryl)acetate, followed by isomer separation and alkaline ester hydrolysis, yielded the desired derivatives (Z)- 8a-g and (E)- 8a-g . The biologically most interesting compound (Z)- 8a is currently undergoing clinical trials.     

Sequential and localized grafting on aliphatic polyester diblock copolymers using alkyne deprotection and click cycloaddition

Diblock copolymers, in which both blocks are composed of aliphatic polyesters, were synthesized from two different alkyne‐functionalized δ‐valerolactone monomers by ring opening polymerization and subsequent click cycloaddition. Trimethylsilyl protection of the alkyne functionality of one block was instrumental to the success of the synthesis. These novel aliphatic polyester diblock copolymers were characterized by ¹H and ¹³C NMR spectroscopy, gel permeation chromatography (GPC), and infrared (IR) spectroscopy. Sequential functionalization of the diblock copolymers with hydrophobic groups on one block, and hydrophilic groups on the other block, provides access to amphiphilic structures. Micellar structures generated from these polyester amphiphiles were characterized by fluorescence spectroscopy and transition electron microscopy (TEM). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

On the scattering frequencies of time-dependent potentials

This paper discusses the scattering frequencies associated with the scalar wave equation and a time-periodic, real, potential. It is shown that the scattering frequencies form a discrete set in the complex plane and depend continuously on the potential. Existence of the scattering frequencies is proved for periodic potentials which are perturbations of a time independent, nonnegative, potential.     

High‐field asymmetric waveform ion mobility spectrometry (FAIMS) coupled with high‐resolution electron transfer dissociation mass spectrometry for the analysis of isobaric phosphopeptides

We have applied high‐field asymmetric waveform ion mobility spectrometry (FAIMS) to the analysis of the phosphopeptides APLpSFRGSLPKSYVK, APLSFRGpSLPKSYVK, and APLSFRGSLPKpSYVK. The peptides have identical amino acid sequences and differ only in the site of phosphorylation. The results show that FAIMS is capable of at least partially separating these species. Separation was confirmed by coupling FAIMS with high‐resolution electron transfer dissociation (ETD) mass spectrometry. Phosphorylation is retained on the ETD peptide fragments thereby allowing assignment of the site of the modification. Co‐eluting phosphopeptides which differ only in the site of modification are frequently observed in liquid chromatography/tandem mass spectrometry phosphoproteomics experiments, and therefore these proof‐of‐principle results have implications for the application of FAIMS in that field. Copyright © 2009 John Wiley & Sons, Ltd.     

Integral equation formulation for buoyancy-driven convection problems

An integral equation formulation for buoyancy-driven convection problems is developed and illustrated. Buoyancy-driven convection in a bounded cylindrical geometry with a free surface is studied for a range of aspect ratios and Nusselt numbers. The critical Rayleigh number, the nature of the cellular motion, and the heat transfer enhancement are computed using linear theory. Green's functions are used to convert the linear problem into linear Fredholm integral equations. Theorems are proved which establish the properties of the eigenvalues and eigenfunctions of the linear integral operator which appears in these equations.     

Synthetic neovibsanes and their ability to induce neuronal differentiation in PC12 cells

A series of neovibsanin A and B derivatives and lower homologues were synthesized to study their neurotrophic ability with PC12 cells. 4,5-Bis-epi-neovibsanin A displayed prominent ability to induce neurite outgrowth compared to control cultures. Herein we describe the total synthesis of 4,5-bis-epi-neovibsanin A and B as well as comparing the biological activity of several neovibsane derivatives.     

A linked electron pair functional

A modification of the variational configuration interaction functional in the first-order interacting space for molecular electronic structure is presented. The modified functional is a fully linked expression that by construction is extensive and invariant to transformations of the underlying orbital basis and is exact for an ensemble of separated two-electron subsystems. In addition, an approximation to variational coupled cluster is generated through truncation of the exponential cluster operator. When combined, these methods demonstrate accuracy that exceeds that of the standard coupled-cluster method, in particular in situations where the reference Slater determinant is not a good approximation.     

Electron capture dissociation mass spectrometry of tyrosine nitrated peptides

In vivo protein nitration is associated with many disease conditions that involve oxidative stress and inflammatory response. The modification involves addition of a nitro group at the position ortho to the phenol group of tyrosine to give 3-nitrotyrosine. To understand the mechanisms and consequences of protein nitration, it is necessary to develop methods for identification of nitrotyrosine-containing proteins and localization of the sites of modification. Here, we have investigated the electron capture dissociation (ECD) and collision-induced dissociation (CID) behavior of 3-nitrotyrosine-containing peptides. The presence of nitration did not affect the CID behavior of the peptides. For the doubly-charged peptides, addition of nitration severely inhibited the production of ECD sequence fragments. However, ECD of the triply-charged nitrated peptides resulted in some singly-charged sequence fragments. ECD of the nitrated peptides is characterized by multiple losses of small neutral species including hydroxyl radicals, water and ammonia. The origin of the neutral losses has been investigated by use of activated ion (AI) ECD. Loss of ammonia appears to be the result of non-covalent interactions between the nitro group and protonated lysine side-chains.     

Zn2+ has a primary hydration sphere of five: IR action spectroscopy and theoretical studies of hydrated Zn2+ complexes in the gas phase

Complexes of Zn(2+)(H(2)O)(n), where n = 6-12, are examined using infrared photodissociation (IRPD) spectroscopy, blackbody infrared radiative dissociation (BIRD), and theory. Geometry optimizations and frequency calculations are performed at the B3LYP/6-311+G(d,p) level along with single point energy calculations for relative energetics at the B3LYP, B3P86, and MP2(full) levels with a 6-311+G(2d,2p) basis set. The IRPD spectrum of Zn(2+)(H(2)O)(8) is most consistent with the calculated spectrum of the five-coordinate MP2(full) ground-state (GS) species. Results from larger complexes also point toward a coordination number of five, although contributions from six-coordinate species cannot be ruled out. For n = 6 and 7, comparisons of the individual IRPD spectra with calculated spectra are less conclusive. However, in combination with the BIRD and laser photodissociation kinetics as well as a comparison to hydrated Cu(2+) and Ca(2+), the presence of five-coordinate species with some contribution from six-coordinate species seems likely. Additionally, the BIRD rate constants show that Zn(2+)(H(2)O)(6) and Zn(2+)(H(2)O)(7) complexes are less stable than Zn(2+)(H(2)O)(8). This trend is consistent with previous work that demonstrates the enthalpic favorability of the charge separation process forming singly charged hydrated metal hydroxide and protonated water complexes versus loss of a water molecule for complexes of n ≤ 7. Overall, these results are most consistent with the lowest-energy structures calculated at the MP2(full) level of theory and disagree with those calculated at B3LYP and B3P86 levels.