Reactive sulfur species and their significance in health and disease.

Reactive sulfur species (RSS) have been recognized in the last two decades as very important molecules in redox regulation. They are involved in metabolic processes and, in this way, they are responsible for maintenance of health. This review summarizes current information about the essential biological RSS, including H2S, low molecular weight persulfides, protein persulfides as well as organic and inorganic polysulfides, their synthesis, catabolism and chemical reactivity. Moreover, the role of RSS disturbances in various pathologies including vascular diseases, chronic kidney diseases, diabetes mellitus Type 2, neurological diseases, obesity, chronic obstructive pulmonary disease and in the most current problem of COVID-19 is presented. The significance of RSS in aging is also mentioned. Finally, the possibilities of using the precursors of various forms of RSS for therapeutic purposes are discussed.

Porous carbon materials derived from discarded COVID-19 masks via microwave solvothermal method for lithium­sulfur batteries.

With the spread of COVID-19, disposable medical masks (DMMs) have become a significant source of new hazardous solid waste. Their proper disposal is not only beneficial to the safety of biological systems but also useful to achieve considerable economic value. The first step of this study was to investigate the chemical composition of DMMs. It is primarily composed of polypropylene, polyethylene terephthalate and iron, with fibrous polypropylene accounting for approximately 80% of the total weight. Then, DMMs were sulfonated and oxidised by the microwave-driven concentrated sulfuric acid within 8 min based on the fact that the concentrated sulfuric acid exhibits a good microwave absorption capacity. The co-doping of sulfur and oxygen was achieved while improving the thermal stability of DMMs. Subsequently, the self-activation pyrolysis of sulfonated and oxidised DMMs (P-SO@DMMs) was further realized in low-flow-rate argon. The specific surface area of P-SO@DMMs increased from 2.0 to 830.9 m2·g-1. P-SO@DMMs sulfur cathodes have promising electrochemical properties because of their porous structures and the synergistic effect of sulfur and oxygen co-doping. The capacity of the samples irradiated by microwave for 10 min at 0.1, 0.2, 0.5, 1, 2 and 5 C were 1313.6, 1010.9, 816.5, 634.4, 513.4 and 453.1 mAh·g-1, respectively, and after returning to 0.2 C and continuing the cycle for 50 revolutions, maintained 50.5% of the initial capacity. After 400 cycles, its capacity is 38.1% of the initial capacity at 0.5 C. It is slightly higher than the electrochemical performance of the sample treated by microwave for 8 min and significantly higher than the sample treated by 6 min. This work converts structurally complex, biohazardous DMMs into porous carbon with high specific surface area by clean and efficient microwave solvothermal and self-activating pyrolysis, which facilitates the development of carbon based materials at low cost and large scale.

Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex. These metal binding sites are essential for replication and for interaction with the viral helicase. Oxidation of the clusters by the stable nitroxide TEMPOL caused their disassembly, potently inhibited the RdRp, and blocked SARS-CoV-2 replication in cell culture. These iron-sulfur clusters thus serve as cofactors for the SARS-CoV-2 RdRp and are targets for therapy of COVID-19.

COVID-19 and the ethnicity link - is there a photochemical link?

A hypothesis is proposed to explain the increased detrimental effect of COVID-19 for Black, Asian and Minority Ethnic (BAME) men and women compared to Caucasian individuals. This is based on the differing photochemistry of phaeomelanin in fair skin and eumelanin in dark/black skin. It is suggested that a range of reactive oxygen species, including, singlet oxygen and the superoxide radical anion, derived via direct photolysis of phaeomelanin, may escape the melanocyte and cause subsequent damage to the SARS-CoV-2 virus. It is further suggested that (large) carbon and sulphur peroxy radicals, from oxygen addition to radicals formed by carbon-sulphur bond cleavage, may assist via damage to the cell membranes. It is also speculated that light absorption by phaeomelanin and the subsequent C-S bond cleavage, leads to release of pre-absorbed reactive oxygen species, such as singlet oxygen and free radicals, which may also contribute to an enhanced protective effect for fair-skinned people.

[Studies on Functional Molecules Based on Peptide Chemistry].

Studies on functional molecules starting from syntheses of cysteine-containing peptides and protein are described. Starting from evaluation of a cysteine specific side-reaction, a specific reaction for disulfide-bond formation was developed. The reaction made it possible to independently construct a disulfide bridge without effecting the existing disulfide bonds, which resulted in a unique approach for the synthesis of human insulin by site-specific disulfide bond formation. In a series of studies on sulfur-containing amino acids, another cysteine related un-natural amino acid, α-methyl cysteine, was used for the total syntheses of natural products containing a unique thiazorine/thiazole ring system. Chloroimidazolidium coupling reagent developed by us was effective for the successive couplings of the α-methyl cysteine residues. Based on these synthetic studies, design and evaluation of protease inhibitors were then studied, since a stereo-specific synthesis of the key structure is crucial to make the inhibitor an effective functional molecule in the interactions with its target protease. As the target proteases, ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) and chymotrypsin-like protease of severe acute respiratory syndrome (SARS 3CL protease) were selected: the former is a crucial enzyme for amyloid ß production and the latter is an essential enzyme for the re-construction of SARS corona virus in host cells. Structure optimization procedure of the respective inhibitors are described based on X-ray crystal structure analyses of the inhibitor-protease complex.