1.Enhanced skin permeation of salicylate by ion-pair formation in non-aqueous vehicle and further enhancement by ethanol and l-menthol.
Abu Hena Mostofa Kamal M;Iimura N;Nabekura T;Kitagawa S Chem Pharm Bull (Tokyo). 2006 Apr;54(4):481-4.
Enhancement of skin permeability of salicylate from non-aqueous vehicle by ion-pair formation with either alkylamines or benzylamine as model cationic ions was examined in excised guinea pig dorsal skin. Solubility of salicylate in isopropyl myristate (IPM) was increased by the addition of either alkylamines or benzylamine as counter ions. The increase was more significant in the presence of amines with longer alkyl chains. Flux of salicylate increased in the presence of these amines due to the increase in the solubility. Maximum flux was observed in the presence of n-hexylamine, which induced an 11-fold increase due to 137-fold increase in solubility. Flux and permeability coefficients of salicylate in the presence of n-butylamine, n-hexylamine, iso-octylamine and benzylamine as counter ions in IPM were larger than those of the non-ionic form of salicylic acid. Flux of 3-methylsalicylate (3-CH3 substituent) and that of 5-hydroxysalicylate (5-OH substituent) were smaller than that of salicylate in the presence of n-hexylamine. After partition to the skin surface, the ion-pair is suggested to dissociate and permeate separately according to the study using lidocaine as the counter ion.
2.Inhibition of human liver microsomal (S)-nicotine oxidation by (-)-menthol and analogues.
MacDougall JM;Fandrick K;Zhang X;Serafin SV;Cashman JR Chem Res Toxicol. 2003 Aug;16(8):988-93.
(-)-Menthol is a widely used flavoring ingredient present in mouthwash, foods, toothpaste, and cigarettes; yet, the pharmacological effects of menthol have not been widely studied. Mentholated cigarette smoking may increase the risk for lung cancer. Many African American smokers smoke mentholated cigarettes, and African Americans have a significantly higher incidence of lung cancer as compared with whites. There may be a relationship between the incidence of lung cancer and the type of cigarette smoked because the use of mentholated cigarettes by white smokers is significantly less and the incidence of lung cancer is less. The mechanism whereby (-)-menthol could increase the health risk of smoking is not known. The results of our in vitro studies herein show that (-)-menthol and synthetic congeners inhibit the microsomal oxidation of nicotine to cotinine and the P450 2A6-mediated 7-hydroxylation of coumarin. Replacement of the alcohol oxygen atom of menthol with other heteroatoms increased the potency of P450 2A6 inhibition. Thus, the K(i) value of (-)-menthol for inhibition of microsomal nicotine oxidation was 69.7 micro M but neomenthyl thiol possesses a K(i) value of 13.8 micro M.
3.Electrochemical investigation of photooxidation processes promoted by sulfo-polyoxometalates: coupling of photochemical and electrochemical processes into an effective catalytic cycle.
Rüther T;Hultgren VM;Timko BP;Bond AM;Jackson WR;Wedd AG J Am Chem Soc. 2003 Aug 20;125(33):10133-43.
Oxidative photocurrents measured upon irradiation by a 7-W visible light (wavelength 312-700 nm) demonstrated that the sulfo-polyoxometalate anion clusters [S2W18O62]4- (1a), [S2Mo18O62]4- (1b), and [SMo12O40]2- (2) may be activated photochemically to oxidize the organic substrates benzyl alcohol, ethanol, and (-)-menthol. In the case of catalytic photooxidation of benzyl alcohol to benzaldehyde in the presence of 1a, quantitative electrochemical methods have identified pathways for the oxidation of reduced forms of 1 generated during the catalysis. More generally, the oxidation pathways P(n+2)- + 2H+ <==> Pn- + H2 and 2P(n+2)- + O2 + 4H+ <==> 2Pn- + 2H2O have been evaluated by monitoring acidified acetonitrile solutions of the 2e(-)-reduced clusters by rotating disk electrode voltammetry under anaerobic and aerobic conditions, respectively. Neither of the reduced forms 1b(2e-) nor 2(2e-) reacted under these conditions. In contrast, 1a(2e-) was oxidized via both pathways, consistent with its more negative redox potential, with the rate of oxidation by air-oxygen being significantly faster than that by H+. The present work demonstrated that the crucial step necessary to oxidize reduced catalyst in photocatalytic reactions involving the anions studied may be achieved or accelerated by application of an external potential more positive than the first redox potential of the polyoxometalate anion.
