The suicide inactivation mechanism of tyrosinase acting on its substrates has been studied. The kinetic analysis of the proposed mechanism during the transition phase provides explicit analytical expressions for the concentrations of o-quinone against time. The electronic, steric and hydrophobic effects of the substrates influence the enzymatic reaction, increasing the catalytic speed by three orders of magnitude and the inactivation by one order of magnitude. To explain the suicide inactivation, we propose a mechanism in which the enzymatic form Eox (oxy-tyrosinase) is responsible for such inactivation. A key step might be the transfer of the C-1 hydroxyl group proton to the peroxide, which would act as a general base. Another essential step might be the axial attack of the o-diphenol on the copper atom. The rate constant of this reaction would be directly related to the strength of the nucleophilic attack of the C-1 hydroxyl group, which depends on the chemical shift of the carbon C-1 (δ1) obtained by 13C-NMR. Protonation of the peroxide would bring the copper atoms together and encourage the diaxial nucleophilic attack of the C-2 hydroxyl group, facilitating the co-planarity with the ring of the copper atoms and the concerted oxidation/reduction reaction, and giving rise to an o-quinone. The suicide inactivation would occur if the C-2 hydroxyl group transferred the proton to the protonated peroxide, which would again act as a general base. In this case, the co-planarity between the copper atom, the oxygen of the C-1 and the ring would only permit the oxidation/reduction reaction on one copper atom, giving rise to copper(0), hydrogen peroxide and an o-quinone, which would be released, thus inactivating the enzyme.

To evaluate the association between prolonged second stage of labor and the risk of adverse neonatal outcomes with a systematic review and meta-analysis. PubMed, Scopus and EMBASE were searched using the search strategy “Labor Stage, Second” AND (length OR duration OR prolonged OR abnormal OR excessive). Observational studies that examine the relationship between prolonged second stage of labor and neonatal outcomes were selected. Prolonged second stage of labor was defined as 4 h or more in nulliparous women and 3 h or more in multiparous women. The main neonatal outcomes were 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal death. Data collection and quality assessment were carried out independently by the three reviewers. Twelve studies were selected including 266,479 women. In nulliparous women, a second stage duration greater than 4 h increased the risk of 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit and neonatal sepsis and intubation. In multiparous women, a second stage of labor greater than 3 h was related to 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity. Prolonged second stage of labor increased the risk of 5 min Apgar score <7 and admission to the Neonatal Intensive Care Unit in nulliparous and multiparous women, without increasing the risk of neonatal death. This review demonstrates that prolonged second stage of labor increases the risk of neonatal complications in nulliparous and multiparous women.