A novel anthracenyl tagged protecting group for "phase-switching" applications in parallel synthesis

A new "phase-switching" protecting group 1 that facilitates the parallel synthesis of carboxylic acids, esters, and carboxamides is described. Its use permits chemistries to be performed in solution, which may be conveniently monitored with conventional analytical techniques, followed by subsequent immobilization onto a solid-phase support to aid compound purification. Carboxylic acids, esters, and carboxamides are then cleaved from the solid support following activation of the "safety-catch" and treatment with the desired nucleophile.     

Effects of deformability, uneven surface charge distributions, and multipole moments on biocolloid electrophoretic migration

Liposomes have been widely used as cellular and bioparticle mimics due to their lipid bilayer structure and relative ease of production and manipulation. Such biocolloids are frequently characterized by capillary electrophoresis (CE), which promises a wealth of information about such properties as surface charge, composition, and rigidity. The applicability of this information is somewhat limited, however, since it is interpreted with colloidal theories that do not account for the unique properties of biocolloids. In this work, the effects of deformability, mobile surface charges, intrinsic polarizability, and uneven surface charge distributions are incorporated into colloidal theories in order to better model the electrophoretic behaviors of liposomes.     

Engineering cytochrome P-450s

Cytochrome P-450 isozymes represent a critical component of nature’s spectrum of detoxification catalysts that could be exploited for bioremediation. The ethanol-inducible human cytochrome P-450 2E1 serves as a model eukaryotic P-450 that complements the bacterial P-450 cam in dehalogenation and detoxification of environmental pollutants. We explored the construction of novel chimeric P-450s using cytochrome P-450 camC and 2E1 genes. For construction of chimera 1 (478 amino acids, 55.14 kDa), 145 amino acids from the N-terminus of P-450 2E1 protein (493 amino acids, 56.84 kDa) were replaced with 130 amino acids from the N-terminus of P-450 camC protein (415 amino acids, 46.66 kDa). In chimera 2 (525 amino acids, 60.24 kDa) the strategy involves replacement of 28 amino acids in the C-terminus of chimera 1 with 75 amino acids from the C-terminus of P-450 camC gene. Homology models of both the chimeric proteins were developed using SWISS-MODEL based on the known crystal structure of cytochrome P-450 camC, BM-3, 1DT6A, and 2C17A. The models indicated that the proposed heme-binding site was intact, which is inevitable for catalytic activity of cytochrome P-450s. The expression of chimera 1 and 2 genes in Escherichia coli DH5α was evident from light-pink cell pellets, protein band in sodium dodecyl sulfate polyacrylamide gel electrophoresis, and diagnostic carbon monoxide-difference spectra. Our studies show that strategies can be developed to exploit the natural diversity of the P-450 superfamily to generate chimeric biocatalysts that would provide new templates amenable to directed evolution.     

Perturbational analysis of the regioselectivity in the acrolein dimerization

Using intermolecular SCF-perturbation theory, the controlling factors determining the regioselectivity in the acrolein dimerization are derived by a rigorous decomposition of the interaction energy. This partitioning of the interaction energy is performed up to a level where a comparison with frontier orbital models is possible. The regioselectivity is found to be determined by orbital interactions occuring via the terminal atoms and atoms involved in secondary Woodward-Hoffmann interactions.     

Hydrogen bonding between solvation shells around gd3+ from cooperative vibronic spectra

Cooperative vibronic spectra involving Gd³⁺ electronic transitions and the vibrational transitions of nearby water molecules are used to determine the stretching spectrum for isotopically dilute OH in a solution of GdCl₃ in D₂O. The OH stretching spectrum of water molecules in the first hydration sphere is shifted to lower energy than that of the bulk liquid.     

The isomerization of optically-active propargyl alcohols to terminal acetylenes.

The isomerization of optically-active secondary propargyl alcohols, RCHOHCC(CH₂)_nCH₃, to terminal acetylenic alcohols, RCHOH(CH₂)_n+1 C=CH, by potassium 3-aminopropylamide (KAPA) proceeds without loss of configuration at the hydroxy center.     

Guest sorption and desorption in the metal-organic framework [Co(INA)(2)] (INA=isonicotinate)--evidence of intermediate phases during desorption

The metal-organic framework [Co(INA)(2)]x0.5EtOH (INA = isonicotinate, NC(5)H(4)-4-CO(2)(-)), was synthesised under solvothermal conditions. Its X-ray crystal structure shows channels containing ethanol guests which are hydrogen-bonded to carboxylate oxygens of the framework. The pyridyl rings of the framework alternate between 'open' and 'closed' positions along the channels resulting in large variation in the channel cross-sectional area from ca. 1.4 by 2.3 A at the narrowest point to 4.9 by 5.3 A at the widest. Despite the very small windows, the ethanol guests (of van der Waals diameter ca. 4.2-6.1 A) may be reversibly desorbed and sorbed into the structure quantitatively, as shown by in situ variable-temperture IR spectroscopy and XRPD. The single-crystal structure of the desolvated form [Co(INA)(2)] shows that there is no change in the overall connectivity on desolvation, but the rotational positions of the pyridine rings are altered. This suggests that pyridyl rotation may occur to allow guests to pass in and out. When the synthesis was conducted in 1-propanol solvent [Co(INA)(2)]x0.5Pr(n)OHxH(2)O, was obtained, and a single-crystal X-ray structure revealed the same overall connectivity as in but with pyridine rings disordered over closed and open positions. There was no evidence of included guests from X-ray crystallography, suggesting that they are also highly disordered. Variable-temperature XRPD performed on bulk samples showed peaks which were unsymmetrical and exhibited shoulders, suggesting that for each pattern obtained the material actually consisted of several closely-related phases. The movements of the peaks during desolvation showed the presence of intermediate phases before the final desolvated product was formed. The peak positions of the intermediate phases matched more closely with the calculated pattern for than with or, suggesting that they may have disordered structures similar to. The results also suggest that the intermediate phase represents an initial increase in volume before a larger decrease in volume occurs to give the final desolvated material.     

Tris(acetonitrile)tricarbonylchromium(0) catalyzed 1,4-addition of hydrogen to 1,3-dienes

The Cr(CO)₃(CH₃CN)₃ complex is found to catalyze the 1,4-addition of hydrogen to 1,3-dienes such as 2-methyl-1,3-butadiene, trans-1,3-pentadiene, and trans, trans-2,4-hexadiene at low temperature (40°) and low H₂ pressure (20 psi). For trans, trans-2,4-hexadiene the only product obtained when D₂ is used is 2,5-dideuterio-cis-3-hexene. The catalytic 1,4-hydrogenation can be carried out in neat dienes, and turnover numbers for the catalyst of greater than 3000 have been observed.     

Experimental and theoretical study of the V → T,R relaxation of CD4 between 300 and 100 K

Rate constants for the vibrational deactivation of CD₄ by the collision partners CD₄, He, Ne, Ar, Kr, D₂ and O₂ have been measured using a laser-fluorescence technique. The results are compared with those for the deactivation of CH₄ by the same collision partners and with a modified SSH type theoretical treatment.     

Evaluation of Poisson solvation models using a hybrid explicit/implicit solvent method

Implicit solvent methods have become popular tools in the field of protein dynamics simulations, yet evaluation of their validity has been primarily limited to comparisons with experimental and theoretical data for small molecules. In this paper, we use a recently developed hybrid explicit/implicit solvent methodology to evaluate the accuracy of several Poisson-based implicit solvent models. Specifically, we focus on the calculation of electrostatic solvation free energies of various fixed conformations for two proteins. We show that, among various dielectric boundary definitions, the Lee-Richards molecular surface has the best agreement with hybrid solvent results. Furthermore, certain modifications of the molecular surface Poisson protocol provide varied results. For instance, simple modifications of atomic radii on charged residues generally improve absolute errors but do not significantly reduce relative errors among conformations. On the other hand, using a water-probe radius of 1.0 A, as opposed to the standard value of 1.4 A, to generate the molecular surface, moderately improves both absolute and relative results.