No abstract

Ruthenium porphyrin complexes such as carbonylruthenium(II) tetrakispentafluorophenylporphyrin [Ru(II)(TPFPP)(CO)] were found to be efficient catalysts for the hydroxylation of alkanes in the presence of 2,6-dichloropyridine N-oxide as the oxidant under mild, nonacidic conditions. Up to 14 800 turnovers (TO) and rates of 800 TO/min were obtained for the hydroxylation of adamantane. The hydroxylation of cis-decalin afforded cis-9-decalol and cis-decalin-9,10-diol, exclusively, thus, excluding a long-lived radicals mechanism. The kinetics of product evolution in a typical catalytic oxygenation showed an initial induction period followed by a fast, apparently zero-order phase with maximum rates and high efficiencies. Deuterium isotope effects (kH/kD) in the range of 4.2-6.4 were found for the hydroxylation of alkanes. A Hammett treatment of the data for the oxidation of para-substituted toluene derivatives showed a linear correlation with a highly negative rho+ value of -2.0. On the basis of kinetic and spectroscopic evidence, Ru(VI)(TPFPP)(O)2, Ru(II)(TPFPP)(CO), and Ru(IV)(TPFPP)Cl2 observed during catalysis were ruled out as candidates for the active catalyst responsible for the high efficiencies and turnover rates in the oxidation reactions. The fastest rates of adamantane hydroxylation with 2,6-dichloropyridine N-oxide were achieved by the reductive activation of Ru(IV)(TPFPP)Cl2 with a zinc amalgam. This redox activation is consistent with the formation of an active Ru(III) intermediate in situ by a one-electron reduction of the Ru(IV) porphyrin. EPR spectra characteristic of Ru(III) have been observed upon the reduction of Ru(IV)(TPFPP)Cl2 with a zinc amalgam. In the adamantane oxidation mediated with Ru(III)(TPFPP)(OEt), it was found that, during this process, the Ru(III) porphyrin was gradually converted to a dioxoRu(VI) porphyrin. Concomitant with this conversion, the reaction rates decreased. Catalyst activation was also stimulated by autoxidation of the solvent CH2Cl2. On the basis of these data, a mechanism is proposed that incorporates a "fast" cycle involving metastable Ru(III) and oxoRu(V) intermediates and a "slow" oxidation cycle, mediated by oxoRu(IV) and trans-dioxoRu(VI) porphyrin complexes.

beta-Cyclodextrin-poly(ethylene glycol)-folic acid conjugate (CD-PEG-FA) was synthesized according to a two-step procedure: (1). synthesis of CD-PEG-NH(2) by reaction of monotosyl-activated beta-cyclodextrin with excess of 700 Da diamino-PEG; (2). synthesis of CD-PEG-FA by reaction of CD-PEG-NH(2) with succinimidyl ester-activated folic acid. The CD-PEG-NH(2) intermediate was purified by precipitation in acetone, and the CD-PEG-FA by gel permeation and C-18 reversed-phase chromatography. Both CD-PEG-NH(2) and CD-PEG-FA were analyzed by mass spectrometry, (1)H NMR, and UV-vis spectroscopy. All analytical methods confirmed the theoretical composition of the conjugates: the CD-PEG-NH(2) intermediate was composed of CD and PEG in the molar ratio of 1:1, and the CD-PEG-FA was composed of beta-cyclodextrin, PEG, and folic acid in the molar ratio of 1:1:1. The CD-PEG-FA conjugate was highly soluble in buffer (>42 mM) as compared to the unmodified beta-cyclodextrin (16.3 mM). Phase solubility diagrams of beta-estradiol revealed that drug solubility increases from 11 microM in buffer to 600 microM in the presence of beta-cyclodextrins and 5900 microM with CD-PEG-FA. However, the affinity of beta-estradiol for beta-cyclodextrins decreased about 4 times with PEG and folic acid conjugation. Stability studies carried out using chlorambucil confirmed that the conjugate partially prevents drug degradation in buffer, although this effect was considerably lower than that obtained with beta-cyclodextrin. Computer modeling studies showed that the folic acid linked to the beta-cyclodextrins through a PEG spacer could partially interact with the cyclodextrin cavity. Finally, CD-PEG-FA displayed reduced hemolytic effect as compared to unmodified beta-cyclodextrin.

In this paper we report the fabrication of thiolene-based microstructured reactors (MRs) that have been specifically designed to include solid-supported reagents within the microchannels network. We propose a convenient solution to realize reversible press-fit, leak-proof interconnects that greatly simplify the MR coupling to the external environment such as capillary tubing, sample reservoirs and pumps. The MRs have been used to carry out the oxidation of alpha-terpinene and methionine using [60]fullerene, covalently linked to Tentage](R) and silica gel matrices, as a singlet oxygen sensitizer. High conversions have been observed for both substrates although, in the case of a-terpinene, a partial photodegradation of the endo-peroxide product was detected. Interestingly, in the case of methionine, a quantitative conversion to the corresponding sulfoxides was achieved in about 40 seconds, using lowpower, white LED illumination. The reaction time is considerably shorter when compared to the batch procedure that requires, for the same process, about one hour illumination and the use of a 300-W tungsten halogen lam