1. Organoplatinum Compounds as Anion-Tuneable Uphill Hydroxide Transporters
Li-Jun Chen, Xin Wu, Alexander M Gilchrist, Philip A Gale Angew Chem Int Ed Engl. 2022 May 2;61(19):e202116355. doi: 10.1002/anie.202116355. Epub 2022 Mar 11.
Active transport of ions uphill, creating a concentration gradient across a cell membrane, is essential for life. It remains a significant challenge to develop synthetic systems that allow active uphill transport. Here, a transport process fuelled by organometallic compounds is reported that creates a pH gradient. The hydrolysis reaction of PtII complexes results in the formation of aqua complexes that established rapid transmembrane movement ("flip-flop") of neutral Pt-OH species, leading to protonation of the OH group in the inner leaflet, generating OH- ions, and so increasing the pH in the intravesicular solution. The organoplatinum complex effectively transports bound hydroxide ions across the membrane in a neutral complex. The initial net flow of the PtII complex into the vesicles generates a positive electric potential that can further drive uphill transport because the electric potential is opposed to the chemical potential of OH- . The OH- ions equilibrate with this transmembrane electric potential but cannot remove it due to the relatively low permeability of the charged species. As a result, effective hydroxide transport against its concentration gradient can be achieved, and multiple additions can continuously drive the generation of OH- against its concentration gradient up to ΔpH>2. Moreover, the external addition of different anions can control the generation of OH- depending on their anion binding affinity. When anions displayed very high binding affinities towards PtII compounds, such as halides, the external anions could dissipate the pH gradient. In contrast, a further pH increase was observed for weak binding anions, such as sulfate, due to the increase of positive electric potential.
2. Bioactive heterocycles containing endocyclic N-hydroxy groups
Reshma Rani, Carlotta Granchi Eur J Med Chem. 2015 Jun 5;97:505-24. doi: 10.1016/j.ejmech.2014.11.031. Epub 2014 Nov 18.
Drug-likeness rules consider N-O single bonds as "structural alerts" which should not be present in a perspective drug candidate. In most cases this concern is correct, since it is known that N-hydroxy metabolites of branded drugs produce reactive species that cause serious side effects. However, this dangerous reactivity of the N-OH species generally takes place when the nitrogen atom is not comprised in a cyclic moiety. In fact, the same type of metabolic behavior should not be expected when the nitrogen atom is included in the ring of an aromatic heterocyclic scaffold. Nevertheless, heterocycles bearing endocyclic N-hydroxy portions have so far been poorly studied as chemical classes that may provide new therapeutic agents. This review provides an overview of N-OH-containing heterocycles with reported bioactivities that may be considered as therapeutically relevant and, therefore, may extend the chemical space available for the future development of novel pharmaceuticals. A systematic treatment of the various chemical classes belonging to this particular family of molecules is described along with a discussion of the biological activities associated to the most important examples.
3. Characterization of Reaction Intermediates Involved in the Water Oxidation Reaction of a Molecular Cobalt Complex
Moumita Bera, Simarjeet Kaur, Kritika Keshari, Dooshaye Moonshiram, Sayantan Paria Inorg Chem. 2022 Dec 26;61(51):21035-21046. doi: 10.1021/acs.inorgchem.2c03559. Epub 2022 Dec 14.
Molecular cobalt(III) complexes of bis-amidate-bis-alkoxide ligands, (Me4N)[CoIII(L1)] (1) and (Me4N)[CoIII(L2)] (2), are synthesized and assessed through a range of characterization techniques. Electrocatalytic water oxidation activity of the Co complexes in a 0.1 M phosphate buffer solution revealed a ligand-centered 2e-/1H+ transfer event at 0.99 V followed by catalytic water oxidation (WO) at an onset overpotential of 450 mV. By contrast, 2 reveals a ligand-based oxidation event at 0.9 V and a WO onset overpotential of 430 mV. Constant potential electrolysis study and rinse test experiments confirm the homogeneous nature of the Co complexes during WO. The mechanistic investigation further shows a pH-dependent change in the reaction pathway. On the one hand, below pH 7.5, two consecutive ligand-based oxidation events result in the formation of a CoIII(L2-)(OH) species, which, followed by a proton-coupled electron transfer reaction, generates a CoIV(L2-)(O) species that undergoes water nucleophilic attack to form the O-O bond. On the other hand, at higher pH, two ligand-based oxidation processes merge together and result in the formation of a CoIII(L2-)(OH) complex, which reacts with OH- to yield the O-O bond. The ligand-coordinated reaction intermediates involved in the WO reaction are thoroughly studied through an array of spectroscopic techniques, including UV-vis absorption spectroscopy, electron paramagnetic resonance, and X-ray absorption spectroscopy. A mononuclear CoIII(OH) complex supported by the one-electron oxidized ligand, [CoIII(L3-)(OH)]-, a formal CoIV(OH) complex, has been characterized, and the compound was shown to participate in the hydroxide rebound reaction, which is a functional mimic of Compound II of Cytochrome P450.
