Reactivity of Singlet Oxygen Toward Proteins: The Effect of Structure in Basic Pancreatic Trypsin Inhibitor and in Ribonuclease A

The reactions of singlet oxygen, ¹O₂, with large peptides have been described previously. It was found that even in these systems, which in their native form are generally not supposed to possess a stable structure in solution, the polypeptide does impede the access of ¹O₂ to the amino acids that react readily with ¹O₂. Here we describe the ¹0₂ reaction with two proteins of well-defined structure. The quenching of ¹O₂ by bovine pancreatic trypsin inhibitor (BPTI) and by ribonuclease A (RNase A) was compared to that of a solution at the same concentration as those of its constituent amino acids that react readily with ¹O₂. The proteins were studied in their native form, when partly denatured by splitting their S-S bonds and when fully denatured. It was found that while in the native form the quenching rate constant was seven times lower in BPTI (2.2 vs 15.2 times 10⁷WM^-1 s^-1) and three times lower in RNase A (11.0 vs 32 times 10⁷M^-l s^-1) than in a mixture of its constituent amino acid residues, it increased upon denaturation reaching in the fully denatured state the value of the corresponding amino acid mixture. More striking is the effect of the protein structure when comparing the fraction of the encounters between ¹O₂ and protein, which cause damage to the protein, as reflected in the decrease of its biological activity. This decrease is assumed to be due to the chemical (oxidative) reactions of ¹O₂ in the protein. In the exceptionally stable BPTI the fraction of such encounters was 0.05 and in RNase A it was 0.2, whereas for the amino acid tryptophan in solution, 0.7 of the collisions with ¹O₂ led to a chemical reaction.     

Vectorization of a classical trajectory code on a floating point systems,Inc. Model 164 attached processor

A triatomic classical trajectory code has been modified by extensive vectorization of the algorithms to achieve much improved performance on an FPS 164 attached processor. Extensive timings on both the FPS 164 and a VAX 11/780 with floating point accelerator are presented as a function of the number of trajectories simultaneously run. The timing tests involve a potential energy surface of the LEPS variety and trajectories with 1000 time steps. The results indicate that vectorization results in timing improvements on both the VAX and the FPS. For larger numbers of trajectories run simultaneously, up to a factor of 25 improvement in speed occurs between VAX and FPS vectorized code.     

Ionic-liquid-supported peptide synthesis demonstrated by the synthesis of Leu(5)-enkephalin

A new strategy for the synthesis of oligopeptides was developed using an ionic liquid as a soluble support. The efficiency of this ionic liquid-phase approach was demonstrated by the synthesis of a bioactive pentapeptide, Leu(5)-enkephalin, in good yield and reasonable purity. The structures and purities of the reaction intermediates in each step were verified easily by routine spectroscopic analysis, and no chromatographic procedures were needed during the synthesis.     

Unusually stable molecular capsule formation of a tetraphenyleneurea cavitand

An unusually stable molecular capsule was formed by heating phenyleneurea-spanned resorcinarene cavitand with 4-methyl-N-p-tolylbenzamide. The molecular capsule behaved as a discrete molecular entity showing a cylindrical D(4d) structure and showed no guest exchange in toluene-d(8) even at 100 degrees C. [structure: see text]     

New membrane materials for potassium-selective ion-sensitive field-effect transistors

Several polymeric materials were studied as membrane materials for potassium-selective ion-sensitive field-effect transistors (ISFETs) to overcome the problems related with the use of conventional plasticized poly(vinyl chloride) membranes casted on ISFET gate surfaces. Several acrylate materials, such as ACE, Epocryl and derivatives, showed no reproducible results. Three room-temperature vulcanizing (RTV)-type silicone rubbers were tested. The addition-type RTV-2 silicone rubber was not suitable as a membrane material, but the condensation-type RTV-1 and especially the RTV-2 silicone rubber showed good results. ISFETs with a Silopren membrane showed a durability of at least 2 months.     

Regioselective cyclomanganation of Schiff bases. An unexpected effect of chloro substituents

In this paper we describe the synthesis of new metallacycles by the cyclomanganation reaction of benzyl-benzylidene-amines by using [MnMe(CO)₅] as metallating agent. These ligands can undergo metallation on different aromatic carbon atoms but no important differences have been found in the regioselectivity of the process, that can be related to the electronic effect of the substituents, and in all the cases studied the endo-cyclomanganated complexes of para-substituted imines have been obtained. The corresponding exo-metallacycles were obtained by reaction of [MnMe(CO)₅] on the imine 2,6-Cl₂C₆H₃CHNCH₂Ph and 2,4,6-Me₃C₆H₂CHNCH₂Ph, derived from 2,6-dichlorobenzaldehyde and 2,4,6-trimethylbenzaldehyde, respectively.The results described suggest that the mechanism of the cyclomanganation is similar to that of cyclopalladation and it can be proposed that cyclomanganation takes place by the formation of a four-centered transition state, involving the C-H and Mn-C_acetyl bonds, in the acetyl coordination complex formed in the first step of the reaction.     

Recent liquid chromatographic-(tandem) mass spectrometric applications in proteomics

Conventional proteomics makes use of two-dimensional gel electrophoresis followed by mass spectrometric analysis of tryptic fragments derived from in-gel digestion of proteins. Although being a very strong technique capable of separating and visualizing hundreds of proteins, 2D-gel electrophoresis has some well-documented disadvantages as well. More recently, liquid chromatographic-(tandem) mass spectrometric techniques have been developed to overcome some of the shortcomings of 2D-gel electrophoresis. In this review we have described several recent applications of liquid chromatography-(tandem) mass spectrometry in the field of proteomics and especially in the field of membrane proteomics, quantitative proteomics and in the analysis of post-translational modifications.     

DFT study and Monte Carlo simulation on proton transfers of 2-amino-2-oxazoline, 2-amino-2-thiazoline, and 2-amino-2-imidazoline in the gas phase and in water

Density functional theory (DFT) and Monte Carlo (MC) simulation with free energy perturbation (FEP) techniques have been used to study the tautomeric proton transfer reaction of 2-amino-2-oxazoline, 2-amino-2-thiazoline, and 2-amino-2-imidazoline in the gas phase and in water. Two reaction pathways were considered: the direct and water-assisted transfers. The optimized structures and thermodynamic properties of stationary points for the title reaction system in the gas phase were calculated at the B3LYP/6-311+G(d, p) level of theory. The potential energy profiles along the minimum energy path in the gas phase and in water were obtained. The study of the solvent effect of water on the proton transfer of 2-amino-2-oxozoline, 2-amino-2-thiazoline, and 2-amino-2-imidazoline indicates that water as a solvent is favorable for the water-assisted process and slows down the rate of the direct transfer pathway.     

Tetrapyrrole derivatives substituted with ferrocenylethynyl moieties. synthesis and electrochemical studies

Up to eight redox-active ferrocenyl units have been incorporated, through the unsaturated ethynyl linkers, on the periphery of a series of cyclic tetrapyrrole derivatives including zinc(II) phthalocyanine and 2,3-naphthalocyanine, and nickel(II) meso-diphenylporphyrin. The synthesis of the former two macrocycles 4 and 7 involves the Sonogashira coupling reaction of ferrocenylethyne with 4,5-dichlorophthalonitrile (1) or 6,7-dibromonaphthalonitrile (5), respectively, followed by a base-promoted cyclization. The meso-bis(ferrocenylethynyl)porphyrin 11 has been prepared from the dibromo analogue 10 also by a palladium-catalyzed coupling reaction. These novel macrocyclic compounds have been spectroscopically and electrochemically characterized. As revealed by cyclic voltammetry, the ferrocenyl moieties appear to be electrochemically independent in these complexes and there is no significant electronic coupling among the iron(II) centers.     

Theoretical Definition of a Functional Group and the Molecular Orbital Paradigm

It is the purpose of this review to demonstrate that the empirical classification of the observations of chemistry in terms of the properties assigned to functional groups is a consequence of and is predicted by physics. This is accomplished by showing that the atoms and functional groups of chemistry can be identified with bounded space-filling objects whose properties are defined by quantum mechanics. The quantum mechanical definition of a group is combined with a new pictorial representation of its form to obtain a unified picture which should make it eminently recognizable to chemists. This picture, when combined with the demonstrated ability of these groups to recover the measured properties of atoms in molecules, is offered as one which meets the expectations a chemist associates with the concept of a functional group. The manner in which this physical definition of a group differs fundamentally from models of functional groups based upon molecular orbital theory is discussed.