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A series of chiral HCNN ligands ((S)-1b−g) (S)-2-(1-aminoethyl)-6-(aryl)pyridine (aryl = 4-MeO-phenyl, 1b; 4-CF3-phenyl, 1c; 3,5-di-Me-phenyl, 1d; 3,5-di-CF3-phenyl, 1e; 1-naphthyl, 1f; 2-naphthyl, 1g) were synthesized starting from commercial 2-acetyl-6-bromopyridine (2), by a chemoenzymatic method involving the dynamic kinetic resolution of the corresponding secondary alcohol (rac-3). The conversion of the resulting (R)-3, obtained in 98% ee, into the homochiral amine ((S)-6), followed by Suzuki coupling with the appropriate arylboronic acids 7b−g, gave access to (S)-1b−g, isolated in 97% ee, with an overall yield up to 50%. The in situ generated pincer complexes [MCl(CNN)(PP)] (M = Ru, Os; PP = Josiphos diphosphine), prepared from [MCl2(PPh3)3], (R,S)-Josiphos diphosphines, and the ligands (S)-1b−g, were found to efficiently catalyze the asymmetric transfer hydrogenation of acetophenone in 2-propanol at 60 °C and in the presence of NaOiPr. On the basis of these data, the 2-naphthyl ruthenium and osmium derivatives [RuCl(CNN)((R,S)-Josiphos*)] (8) (HCNN = (S)-1g) and [OsCl(CNN)(PP)] (PP = (R,S)-Josiphos, 9, and (R,S)-Josiphos*, 10) were isolated from [MCl2(PPh3)3], (R,S)-Josiphos diphosphines, and the ligand (S)-1g. Complexes 8 and 10, displaying the correctly matched chiral PP and CNN− ligands, are highly active and productive catalysts for the transfer hydrogenation of alkyl aryl ketones and methyl pyridyl ketones with TOF = 105−106 h−1, using 0.005 mol % of catalysts and achieving up to 99% ee. The comparison of the catalytic activity of these pincer complexes shows that Ru and Os derivatives display similar rate and enantioselectivity

Photobiomodulation (PBM) is emerging as an effective strategy for the management of multiple inflammatory conditions, including oral mucositis (OM) in cancer patients who receive chemotherapy or radiotherapy. Still, the poor understanding of the mechanisms by which the light interacts with biological tissues and the heterogeneity of light sources and protocols employed worldwide significantly limits its applicability. Reactive oxygen species (ROS) are massively generated during the early phases of OM and play a major role in the pathogenesis of inflammation in general. Here, we report the results of a clinical and experimental study, aimed at evaluating the effect of laser light at different wavelengths on oxidative stress in vivo in oncologic patients suffering from OM and in vitro in two cell types abundantly present within the inflamed oral mucosa, neutrophil polymorphonuclear (PMN) granulocytes, and keratinocytes. In addition to standard ROS detection methods, we exploited a roGFP2-Orp1 genetically encoded sensor, allowing specific, quantitative, and dynamic imaging of redox events in living cells in response to oxidative stress and PBM. We found that the various wavelengths differentially modulate ROS production. In particular, the 660 nm laser light increases ROS production when applied either before or after an oxidative stimulus. In contrast, the 970 nm laser light exerted a moderate antioxidant activity both in the saliva of OM patients and in both cell types. The most marked reduction in the levels of ROS was detected in cells exposed either to the 800 nm laser light or to the combination of the three wavelengths. Overall, our study demonstrates that PBM exerts different effects on the redox state of both PMNs and keratinocytes depending on the used wavelength and prompts the validation of a multiwavelength protocol in the clinical settings.

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Chiral, nonracemic pincer ligands based on the 6-phenyl-2-aminomethylpyridine and 2-aminomethylbenzo[h]quinoline scaffolds were obtained by a chemoenzymatic approach starting from 2-pyridyl and 2-benzoquinolyl ethanone. In the enantiodifferentiating step, secondary alcohols of opposite absolute configuration were obtained by a baker's yeast reduction of the ketones and by lipase-mediated dynamic kinetic resolution of the racemic alcohols. Their transformation into homochiral 1-methyl-1-heteroarylethanamines occurred without loss of optical purity, giving access to pincer ligands used in enantioselective catalysis.