Biomedical subjects

P H Toy

Publications and source records attributed to P H Toy.

6 recordsLinked to original sources

PubMed2000

Soluble polymer bound cleavage reagents: a multipolymer strategy for the cleavage of tertiary amines from REM resin.

Soluble polymer bound reagent 1 has been prepared to cleave tertiary amines from REM resin. Normally, amines cleaved from REM resin require extraction or chromatography to remove excess cleavage reagent and its byproducts. The solubility profile of non-crosslinked polystyrene (NCPS) based reagent 1 eliminates the need for such purification and allows for the direct isolation of a library of pure tertiary amines through simple filtration and concentration operations.

Amines↗

PubMed2000

Hypersensitive radical probes and the mechanisms of cytochrome P450-catalyzed hydroxylation reactions.

The title probes are precursors to kinetically calibrated, aryl-substituted cyclopropylcarbinyl radicals that rearrange with picosecond lifetimes. Applications in studies of cytochrome P450-catalyzed hydroxylation reactions are reviewed. Initially confusing results regarding lifetimes of radicals in the hydroxylation reactions were resolved when second-generation probes that distinguish between radicals and cations were employed. The results indicate that two electrophilic oxidizing species are involved in P450-catalyzed hydroxylations, an iron-oxo species that inserts oxygen and a hydroperoxo-iron species that inserts OH(+). The cationic rearrangement products are ascribed to reactions of the protonated alcohol products formed from the latter.

Biochemistry↗

PubMed2000

Soluble polymer-supported organic synthesis.

Soluble polymers have been used as supports for reagent/catalyst immobilization and synthesis. Two polymers are commonly used in this context, linear polystyrene and poly(ethylene glycol). The complementary solubility properties of these polymers allow access to a wide range of chemistries. Parallel and combinatorial libraries of small molecules have been prepared using these polymers, and reagents/catalysts that are easily recovered and recycled have been immobilized on them. To develop soluble polymers with novel properties, bifunctional polymerization initiators have been used in a parallel combinatorial methodology to prepare block copolymers that exhibit unique solubility profiles.

Indicators and Reagents↗

PubMed1999

Oxidation of ultrafast radical clock substrate probes by the soluble methane monooxygenase from Methylococcus capsulatus (Bath).

Radical clock substrate probes were used to assess the viability of a discrete substrate radical species in the mechanism of hydrocarbon oxidation by the soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath). New substituted cyclopropane probes were used with very fast ring-opening rate constants and other desirable attributes, such as the ability to discriminate between radical and cationic intermediates. Oxidation of these substrates by a reconstituted sMMO system resulted in no rearranged products, allowing an upper limit of 150 fs to be placed on the lifetime of a putative radical species. This limit strongly suggests that there is no such substrate radical intermediate. The two enantiomers of trans-1-methyl-2-phenyl-cyclopropane were prepared, and the regioselectivity of their oxidation to the corresponding cyclopropylmethanol and cyclopropylphenol products was determined. The results are consistent with selective orientation of the two enantiomeric substrates in the hydrophobic cavity at the active site of sMMO, specific models for which were examined by molecular modeling.

Binding Sites↗

PubMed1998

Hypersensitive radical probe studies of chloroperoxidase-catalyzed hydroxylation reactions.

The oxidation of hypersensitive radical probes by chloroperoxidase from Caldariomyces fumago (CPO) was studied in an attempt to "time" a putative radical intermediate. Oxidation of (trans-2-phenylcyclopropyl)methane, previously studied by Zaks and Dodds [Zaks, A., and Dodds, D. R. (1995) J. Am. Chem. Soc. 115, 10419-10424] was reinvestigated. Unrearranged oxidation products were found as previously reported, and control experiments demonstrated that the cyclic alcohol from oxidation at the cyclopropylcarbinyl position, while subject to further oxidation, survives CPO oxidation as detectable species. However, in contrast to the report by Zaks and Dodds, the rearranged alcohol product expected from ring opening of a cyclopropylcarbinyl radical intermediate was shown to be unstable toward the enzyme oxidation reaction. Because of this instability, two new hypersensitive radical probes, (trans-2-phenylcyclopropyl)ethane and 2-(trans-2-phenylcyclopropyl)propane, and their potential cyclic and acyclic products from oxidation at the cyclopropylcarbinyl position were synthesized and tested. Oxidation of both of these probes at the cyclopropylcarbinyl position by CPO gave unrearranged alcohol products only, but control experiments again demonstrated that the rearranged alcohol products were unstable toward CPO oxidation conditions. From the combination of the probe and control studies, the lifetime of a putative radical intermediate must be less than 3 ps. Whereas the results are consistent with an insertion mechanism for production of alcohol product, they do not exclude a very short-lived intermediate.

Catalysis↗

PubMedDate not supplied

Polytetrahydrofuran cross-linked polystyrene resins for solid-phase organic synthesis.

Currently, divinylbenzene cross-linked polystyrene (DVB-PS) is the polymer of choice for use in solid-phase organic synthesis (SPOS). While much research has been directed toward the optimization of linker groups for the attachment of compounds to the polymer, the development of new polymers themselves has been relatively neglected. In an attempt to overcome the shortcomings of DVB-PS and to develop new polymers with optimum properties for use in organic synthesis, we have prepared a series of polystyrene polymers that incorporate flexible polytetrahydrofuran (PTHF) based cross-linkers. The objective of incorporating PTHF into the polymers was to slightly increase the overall polarity of the polymer and thus render the resins more organic solvent-like. Since the degree to which a resin swells in and absorbs a particular solvent correlates to how well substrates attached to the polymer are solvated, we compared the swelling of our new resins to commercially available DVB-PS resins. In all cases, we found that our resins swelled to a much greater extent than do DVB-PS resins, and their use should therefore allow for SPOS reaction conditions that more closely mimic homogeneous solution-phase conditions. It was also found that the PTHF chain length of the cross-linker does not affect the level of swelling since all of our cross-linkers afford resins with comparable levels of increased swelling. Furthermore, we have examined the utility of our resins in directed ortho-metalation reactions and found that the increased swelling of our resins allows for isolation of reaction products in yields comparable to what is achieved using standard solution-phase conditions.

Combinatorial Chemistry Techniques↗