Comparison Of pKa Values Research Articles

Mechanistic Insights into Nitrile Activation by Cobalt(III)-Hydroperoxo Intermediates: The Influence of Ligand Basicity.

The versatile applications of nitrile have led to the widespread use of nitrile activation in the synthesis of pharmacologically and industrially valuable compounds. We reported the activation of nitriles using mononuclear cobalt(III)-hydroperoxo complexes, [CoIII(Me3-TPADP)(O2H)(RCN)]2+ [R = Me (2) and Ph (2Ph)], to form cobalt(III)-peroxyimidato complexes, [CoIII(Me3-TPADP)(R-C(=NH)O2)]2+ [R = Me (3) and Ph (3Ph)]. The independence of the rate on the nitrile concentration and the positive Hammett value of 3.2(2) indicated that the reactions occur via an intramolecular nucleophilic attack of the hydroperoxide ligand to the coordinated nitrile carbon atom. In contrast, the previously reported cobalt(III)-hydroperoxo complex, [CoIII(TBDAP)(O2H)(CH3CN)]2+ (2TBDAP), exhibited the deficiency of reactivity toward nitrile. The comparison of pKa values and redox potentials of 2 and 2TBDAP showed that Me3-TPADP had a stronger ligand field strength than that of TBDAP. The density functional theory calculations for 2 and 2TBDAP support that the strengthened ligand field in 2 is mainly due to the replacement of two tert-butyl amine donors in TBDAP with methyl groups in Me3-TPADP, resulting in the compression of the Co-Nax bond lengths. These results provide mechanistic evidence of nitrile activation by the cobalt(III)-hydroperoxo complex and indicate that the basicity dependent on the ligand framework contributes to the ability of nitrile activation.

Connexin diversity and gap junction regulation by pHi.

The molecular mechanisms controlling pH-sensitivity of gap junctions formed of two different connexins are yet to be determined. We used a proton-sensitive fluorophore and electrophysiological techniques to correlate changes in intracellular pH (pHi) with electrical coupling between connexin-expressing Xenopus oocytes. The pH sensitivities of alpha 3 (connexin46), alpha 2 (connexin38), and alpha 1 (connexin43) were studied when these proteins were expressed as: 1) nonjunctional hemichannels (for alpha 3 and alpha 2), 2) homotypic gap junctions, and 3) heterotypic gap junctions. We found that alpha 3 hemichannels are sensitive to changes in pHi within a physiological range (pKa = 7.13 +/- 0.03; Hill coefficient = 3.25 +/- 1.73; n = 8; mean +/- SEM); an even more alkaline pKa was obtained for alpha 2 hemichannels (pKa = 7.50 +/- 0.03; Hill coefficient = 3.22 +/- 0.66; n = 13). The pH sensitivity curves of alpha 2 and alpha 3 homotypic junctions were indistinguishable from those recorded from hemichannels of the same connexin. Based on a comparison of pKa values, both alpha 3 and alpha 2 gap junctions were more pHi-dependent than alpha 1. The pH sensitivity of alpha 2-containing heterotypic junctions could not be predicted from the behavior of the two connexons in the pair. When alpha 2 was paired with alpha 3, the pH sensitivity curve was similar to that obtained from alpha 2 homotypic pairs. Yet, pairing alpha 2 with alpha 1 shifted the curve similar to homotypic alpha 1 channels. Pairing alpha 2 with a less pH sensitive mutant of alpha 1 (M257) yielded the same curve as when alpha 1 was used. However, the pH sensitivity curve of alpha 3/alpha 1 channels was similar to alpha 3/alpha 3, while alpha 3/M257 was indistinguishable from alpha 3/alpha 1. Our results could not be consistently predicted by a probabilistic model of two independent gates in series. The data show that dissimilarities in the pH regulation of gap junctions are due to differences in the primary sequence of connexins. Moreover, we found that pH regulation is an intrinsic property of the hemichannels, but pH sensitivity is modified by the interactions between connexons. These interactions should provide a higher level of functional diversity to gap junctions that are formed by more than one connexin.