The palladium­(II)-mediated chemical uncaging reaction of propargylic substrates is a recent addition to the field of chemical biology and medicinal chemistry in the activation of bio and prodrug molecules. Most of the strategies used involve C–O bond breaking in molecules bearing protected amino and hydroxyl groups. Although this reaction has been known for many decades, its catalytic cycle in aqueous milieu remains unclear. Our mechanistic investigation results unveil that full propargylic substrate conversion occurs through biphasic kinetics of different rates, where the fastest reaction phase involves a Pd­(II) anti-Markovnikov hydration of the propargyl moiety, followed by the C–O bond breaking through a β-O elimination and lasts only for two turnovers due to product inhibition. The second slower reaction phase involves the hydrolysis of the substrate promoted by Pd(0) species formed during the first phase of the reaction. These findings are crucial for the potential development of bioorthogonal Pd catalysts for the uncaging of propargylic protected bioactive and drugs molecules.

Cu I /TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidinyloxyl) catalyst systems are versatile catalysts for aerobic alcohol oxidation reactions to selectively yield aldehydes. However,several aspects of the mechanism are yet unresolved, mainly because of the lack of identification of any reactive intermediates.H erein, we report the synthesis and characterization of adinuclear [L1 2 Cu 2 ] 2+ complex 1,whichinpresence of TEMPO can couple the catalytic 4H + /4 e À reduction of O 2 to water to the oxidation of benzylic and aliphatic alcohols.The mechanisms of the O 2 -reduction and alcohol oxidation reactions have been clarified by the spectroscopic detection of the reactive intermediates in the gas and condensed phases,aswell as by kinetic studies on each step in the catalytic cycles.Bis(moxo)dicopper(III) (2)and bis(m-hydroxo)dicopper(II) species 3 are shown as viable reactants in oxidation catalysis.T he present study provides deep mechanistic insight into the aerobic oxidation of alcohols that should serve as av aluable foundation for ongoing efforts dedicated towards the understanding of transition-metal catalysts involving redox-active organic cocatalysts.

Cervical cancer is the fourth most common neoplasia in women and the infection with human papilloma virus (HPV) is its necessary cause. Screening methods, currently based on cytology and HPV DNA tests, display low specificity/sensitivity, reducing the efficacy of cervical cancer screening programs. Herein, molecular signatures of cervical cytologic specimens revealed by liquid chromatography-mass spectrometry (LC-MS), were tested in their ability to provide a metabolomic screening for cervical cancer. These molecules were tested whether they could clinically differentiate insignificant HPV infections from precancerous lesions. For that, high-grade squamous intraepithelial lesions (HSIL)-related metabolites were compared to those of no cervical lesions in women with and without HPV infection. Samples were collected from women diagnosed with normal cervix (N = 40) and from those detected with HSIL from cytology and colposcopy (N = 40). Liquid-based cytology diagnosis, DNA HPV-detection test, and LC-MS analysis were carried out for all the samples. The same sample, in a customized collection medium, could be used for all the diagnostic techniques employed here. The metabolomic profile of cervical cancer provided by LC-MS was found to indicate unique molecular signatures for HSIL, being two ceramides and a sphingosine metabolite. These molecules occurred independently of women’s HPV status and could be related to the pre-neoplastic phenotype. Statistical models based on such findings could correctly discriminate and classify HSIL and no cervical lesion women. The results showcase the potential of LC-MS as an emerging technology for clinical use in cervical cancer screening, although further validation with a larger sample set is still necessary.

Reactivities of non-heme iron(IV)-oxo complexes are mostly controlled by the ligands.C omplexes with tetradentate ligands such as [(TPA)FeO] 2+ (TPA = tris(2-pyridylmethyl)amine) belong to the most reactive ones.Here,weshow af ine-tuning of the reactivity of [(TPA)FeO] 2+ by an additional ligand X(X= CH 3 CN,CF 3 SO 3 À ,ArI, and ArIO;ArI = 2-(t BuSO 2)C 6 H 4 I) attached in solution and reveal at hus far unknown role of the ArIO oxidant. The HATr eactivity of [(TPA)FeO(X)] +/2+ decreases in the order of X: ArIO > MeCN > ArI % TfO À .Hence,ArIO is not just amere oxidant of the iron(II) complex, but it can also increase the reactivity of the iron(IV)-oxo complex as alabile ligand. The detected HAT reactivities of the [(TPA)FeO(X)] +/2+ complexes correlate with the Fe = Oand FeO À Hstretching vibrations of the reactants and the respective products as determined by infrared photodissociation spectroscopy. Hence,t he most reactive [(TPA)FeO-(ArIO)] 2+ adduct in the series has the weakest Fe=Obond and forms the strongest FeOÀHb ond in the HATreaction. Scheme 1. Iron(IV)-oxo complexes formed by oxidation of [(TPA)Fe II-(TfO) 2 ]w ith ArIO (ArI = 2-(t BuSO 2)C 6 H 4 I).

Aldehyde deformylation reactions by metal dioxygen adducts have been proposed to involve peroxyhemiacetal species as key intermediates. However, direct evidence of such intermediates has not been obtained to date. We report the spectroscopic characterization of a mononuclear cobalt(III)-peroxyhemiacetal complex, [Co(Me 3 -TPADP)(O 2 CH(O)CH(CH 3 )C 6 H 5 )] + ( 2 ), in the reaction of a cobalt(III)-peroxo complex ( 1 ) with 2-phenylpropionaldehyde (2-PPA). The formation of 2 is also investigated by isotope labeling experiments and kinetic studies. The conclusion that the peroxyhemiacetalcobalt(III) intermediate is responsible for the aldehyde deformylation is supported by the product analyses. Furthermore, isotopic labeling suggests that the reactivity of the cobalt(III)-peroxo complex depends on the second reactant. The aldehyde inserts between the oxygen atoms of 1 , whereas the reaction with acyl chlorides proceeds by a nucleophilic attack. The observation of the peroxyhemiacetal intermediate provides significant insight into the initial step of aldehyde deformylation by metalloenzymes.