Kinetic studies with alternative significance

Of course carbene C-H insertion reactions are well known absolute kinetics have been reported for the insertions of ArCCl into isooctane, cyclohexane, and n-hexane,67 and of PhCCl into Si-H, Sn-H, and C-H bonds.68 More recently, detailed studies have appeared of PhCCl insertions into a variety of substrates bearing tertiary C-H bonds, especially adamantane derivatives.69 Nevertheless, because QMT is considered important in the low temperature solution reactions of MeCCl,60,63 and is almost certainly involved in the cryogenic matrix reactions of benzylchlorocarbene,59 its possible intervention in the low temperature solution reactions of the latter is a real possibility. We are therefore faced with two alternative explanations for the Arrhenius curvature exhibited by benzylchlorocarbene in solution at temperatures < 0°C either other classical reactions (besides 1,2-H shift) become competitive (e.g., solvent insertion, azine formation), or QMT becomes significant.7,59,66... 

Given that hydroxylamine reacts rapidly with heme proteins and other oxidants to produce NO [53], the hydrolysis of hydroxyurea to hydroxylamine also provides an alternative mechanism of NO formation from hydroxyurea, potentially compatible with the observed clinical increases in NO metabolites during hydroxyurea therapy. Incubation of hydroxyurea with human blood in the presence of urease results in the formation of HbNO [122]. This reaction also produces metHb and the NO metabolites nitrite and nitrate and time course studies show that the HbNO forms quickly and reaches a peak after 15 min [122]. Consistent with earlier reports, the incubation ofhy-droxyurea (10 mM) and blood in the absence of urease or with heat-denatured urease fails to produce HbNO over 2 h and suggests that HbNO formation occurs through the reactions of hemoglobin and hydroxylamine, formed by the urease-mediated hydrolysis of hydroxyurea [122]. Significantly, these results confirm that the kinetics of HbNO formation from the direct reactions of hydroxyurea with any blood component occur too slowly to account for the observed in vivo increase in HbNO and focus future work on the hydrolytic metabolism of hydroxyurea. 

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