Fast trigonal/tetragonal interconversion followed by slow chelate-ring closure in the complexation of boronic acids

Which of the step is rate determining in the complexation of boronic acid with bidentate ligands, the first trigonal/tetragonal interconversion step or the following chelate-ring closure step ? No one could have ever answered this simple question clearly. In this study, we for the first time gave an explicit answer to this question. Reaction systems were devised for kinetic measurements to answer this simple question. At first, pK_a values of 15 boronic acids were determined spectrophotometrically at I = 1.0 M and 25 °C: pK_a = 6.40 ± 0.06 for 3,5-Cl₂PhB(OH)₂, 6.62 ± 0.03 for 3,5-(CF₃)₂PhB(OH)₂, 6.95 ± 0.09 for 3,5-Br₂PhB(OH)₂, 7.04 ± 0.03 for 3-NO₂PhB(OH)₂, 7.08 ± 0.03 for 3,5-F₂PhB(OH)₂, 7.12 ± 0.02 for 2,4-F₂PhB(OH)₂, 7.39 ± 0.02 for 4-CF₃PhB(OH)₂, 7.50 ± 0.02 for 3-FPhB(OH)₂, 7.83 ± 0.02 for 2-FPhB(OH)₂, 7.87 ± 0.01 for 3-CF₃PhB(OH)₂, 8.11 ± 0.01 for 2-ClPhB(OH)₂, 8.14 ± 0.03 for 3-(COOH)PhB(OH)₂, 8.15 ± 0.03 for 3-(CH₃CO)Ph(OH)₂, 8.20 ± 0.01 for 3-ClPhB(OH)₂, and 8.66 ± 0.05 for 4-FPhB(OH)₂. The kinetic results for the reactions of some of these boronic acids with 4-isopropyltropolone clearly show that the rate-determining step is not the interconversion step but the chelate-ring closure step.     

Effect of time-varying load on degree of bronchoconstriction in the dog

It is wellestablished that the degree of airway smooth muscle shortening producedby a given dose of bronchial agonist is greatly affected by lungvolume. The airways are tethered by parenchymal attachments, thetension of which increases progressively with lung volume, therebypresenting a commensurately increasing hindrance to smooth musclecontraction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska,and R. A. Murphy. Science 211:495-497, 1981) presented evidence that smooth muscle contractioninitially involves rapidly cycling cross bridges, whichthen change to noncycling (latch) bridges. They also suggested thatmost of the muscle shortening occurs during the early rapidcross-bridge phase. This implies that smooth muscle subject to a givenload early in contraction should shorten less than when it is subjectto the same load later on. An in vitro study (W. Li and N. L. Stephens.Can. J. Physiol. Pharmacol. 72:1458-1463, 1994) obtained support for this notion. To test thishypothesis in vivo, we measured the changes in lung impedance at 1 and6 Hz produced in dogs by a bolus intravenous injection of methacholinewhen lung volume was increased for 10 s at different times afterinjection. We found that the changes in mechanics were greatlyinhibited, whereas lung volume was elevated. However, when lung volumewas returned to its initial level, the lung mechanics continued tochange at a rate unaffected by the preceding volume change. We concludethat temporary mechanical inhibition of airway smooth muscle shorteningin the normal dog in vivo merely delays an otherwise normal course ofcontraction.