Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Novel fluorescent probes based on sulfur and nitrogen co-doped carbon dots for determination of three N-substituted phenothiazine derivatives in dosage forms.

In the current work, sulfur and nitrogen co-doped carbon dots (S,N-CDs) as simple, sensitive, and selective turn-off fluorescent nanosensors were utilized for analysis of three phenothiazine derivatives, including acetophenazine (APZ), chlorpromazine (CPH), and promethazine (PZH). S,N-CDs were synthesized through a green one-pot microwave-assisted technique using widely available precursors (thiourea and ascorbic acid). HRTEM, EDX, FTIR spectroscopy, UV-Vis absorption spectroscopy, and fluorescence spectroscopy were used to characterize the as-synthesized CDs. When excited at 330 nm, the carbon dots produced a maximum emission peak at 410 nm. The cited drugs statically quenched the S,N-CDs fluorescence as revealed by the Stern-Volmer equation. The current method represents the first spectrofluorimetric approach for the determination of the studied drugs without the need for chemical derivatization or harsh reaction conditions. The importance of the proposed work is magnified as the cited drugs do not have any fluorescent properties. The fluorescence of the developed sensor exhibited a linear response to APZ, CPH, and PZH in the concentration ranges of 5.0-100.0, 10.0-100.0, and 10.0-200.0 µM with detection limits of 1.53, 1.66, and 2.47 µM, respectively. The developed fluorescent probes have the advantages of rapidity and selectivity for APZ, CPH, and PZH analysis in tablets with acceptable % recoveries of (98.06-101.66 %). Evaluation of the method's greenness was performed using the Complementary Green Analytical Procedure Index (ComplexGAPI) and Analytical GREEnness metric (AGREE) metrics, indicating that the method is environmentally friendly. Validation of the proposed method was performed according to ICHQ2 (R1) guidelines.

Unveiling the Chemical Composition of Sulfur-Fumigated Herbs: A Triple Synthesis Approach Using UHPLC-LTQ-Orbitrap MS-A Case Study on Steroidal Saponins in Ophiopogonis Radix.

Ophiopogonis Radix (OR) is a traditional Chinese medicine. In recent years, in order to achieve the purpose of drying, bleaching, sterilizing and being antiseptic, improving appearance, and easy storage, people often use sulfur fumigation for its processing. However, changes in the chemical composition of medicinal herbs caused by sulfur fumigation can lead to the transformation and loss of potent substances. Therefore, the development of methods to rapidly reveal the chemical transformation of medicinal herbs induced by sulfur fumigation can guarantee the safe clinical use of medicines. In this study, a combined full scan-parent ions list-dynamic exclusion acquisition-diagnostic product ions analysis strategy based on UHPLC-LTQ-Orbitrap MS was proposed for the analysis of steroidal saponins and their transformed components in sulfur-fumigated Ophiopogonis Radix (SF-OR). Based on precise mass measurements, chromatographic behavior, neutral loss ions, and diagnostic product ions, 286 constituents were screened and identified from SF-OR, including 191 steroidal saponins and 95 sulfur-containing derivatives (sulfates or sulfites). The results indicated that the established strategy was a valuable and effective analytical tool for comprehensively characterizing the material basis of SF-OR, and also provided a basis for potential chemical changes in other sulfur-fumigated herbs.

Selection and application of aptamers for p-hydroxybenzyl hydrogen sulfite after Gastrodia elata Bl. fumigated with sulfur.

Gastrodia elata Bl. is a widely used traditional Chinese medicine known for its medicinal properties. However, during the drying process, G. elata is often fumigated with sulfur to prevent corrosion and improve its appearance. Sulfur-fumigation can result in a reduction in the effective components of the herb and can also be hazardous to human health due to the remaining sulfur dioxide. Sulfur-fumigation of G. elata poses a significant challenge to both end-users and researchers. The detection of p-hydroxybenzyl hydrogen sulfite (p-HS) is a useful tool in determining whether G. elata has been fumigated with sulfur. Unfortunately, the current method for detecting p-HS is costly and requires sophisticated instruments. Therefore, there is a need to develop a more cost-effective and user-friendly method for the detection of p-HS. This study utilized the Capture-SELEX technique to screen high-affinity aptamers for p-HS, which were subsequently characterized by isothermal titration calorimetry (ITC). An aptamer sequence (seq 6) with a high affinity of Kd = 26.5 µM was obtained following 8 rounds of selection against p-HS. With the aptamer serving as the recognition element and gold nanoparticles as the colorimetric indicator, a simple and efficient colorimetric sensor was developed for the specific detection of p-HS. This detection method exhibited a limit of detection of 1 µg/ml, while the p-HS recoveries demonstrated a range of between 88.5 % and 105 % for samples of G. elata obtained in the market. In summary, the aptamer exhibited a high affinity for p-HS, and the sensor developed through the use of a colloidal gold detector based on nucleic acid aptamer can be utilized for rapid detection of sulfur-fumigated G. elata. With these findings, this research paper provides valuable scientific insights and highlights significant potential for future studies in this area.

An XAS study of Hg(II) sorption to Al-based drinking water treatment residuals.

Drinking water treatment residuals (DWTRs) are produced from the coagulation and flocculation processes in conventional drinking water treatment. The abundant metal oxide content of these materials resulting from the use of coagulants, like alum and ferric chloride, has driven strong research interest into the reuse of DWTRs as sorptive materials. Using a suite of aluminum-based DWTRs, we provide new insights into Hg(II) sorption mechanisms. Experiments performed at circum-neutral pH show that sorption capacities are related to the amount of organic carbon/matter present in DWTRs. We found that carbon rich samples can scavenge about 9000 mg/kg of Hg, in contrast to 2000 mg/kg for lime based DWTRs. X-ray absorption spectroscopy (XAS) at the Hg L3 edge further characterizes mercury coordination. X-ray absorption near edge structure (XANES) and extended x-ray absorption fine structure (EXAFS) results point to a partial association of mercury with sulfur at low mass loadings, transitioning to a full association with oxygen/carbon at higher concentrations of sorbed Hg(II) and in DWTRs with limited sulfur content. These results suggest that sorption of Hg(II) is primarily controlled by the carbon/organic matter fraction of DWTRs, but not by the coagulants.

Impacts of sulfur fumigation on the chemistry and immunomodulatory activity of polysaccharides in ginseng.

Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.

Selenium in Peptide Chemistry.

In recent years, researchers have been exploring the potential of incorporating selenium into peptides, as this element possesses unique properties that can enhance the reactivity of these compounds. Selenium is a non-metallic element that has a similar electronic configuration to sulfur. However, due to its larger atomic size and lower electronegativity, it is more nucleophilic than sulfur. This property makes selenium more reactive toward electrophiles. One of the most significant differences between selenium and sulfur is the dissociation of the Se-H bond. The Se-H bond is more easily dissociated than the S-H bond, leading to higher acidity of selenocysteine (Sec) compared to cysteine (Cys). This difference in acidity can be exploited to selectively modify the reactivity of peptides containing Sec. Furthermore, Se-H bonds in selenium-containing peptides are more susceptible to oxidation than their sulfur analogs. This property can be used to selectively modify the peptides by introducing new functional groups, such as disulfide bonds, which are important for protein folding and stability. These unique properties of selenium-containing peptides have found numerous applications in the field of chemical biology. For instance, selenium-containing peptides have been used in native chemical ligation (NCL). In addition, the reactivity of Sec can be harnessed to create cyclic and stapled peptides. Other chemical modifications, such as oxidation, reduction, and photochemical reactions, have also been applied to selenium-containing peptides to create novel molecules with unique biological properties.

Impact of sulfur-fumigation on carbohydrate components of Atractylodis Macrocephalae Rhizoma.

Atractylodis Macrocephalae Rhizoma (AMR) is one of commonly used medicinal and edible herbs in China. It is often sulfur-fumigated during post-harvest processing. Carbohydrates are important active components of AMR. However, it is unknown whether sulfur-fumigation would induce changes on carbohydrates. Here, carbohydrates including polysaccharides, oligosaccharides and free monosaccharides were comprehensively analyzed to characterize the quality changes of sulfur-fumigated AMR. Determination of both homemade sulfur-fumigated AMR samples and commercial samples from market revealed that sulfur-fumigation did not affect molecular weight distribution of polysaccharides, but altered polysaccharides content and its ratios of constituent monosaccharides, especially glucose (Glc) and fructose (Fru), as well as the contents of oligosaccharides DP2-10 and free monosaccharide Fru. Moreover, the variations enhanced with the increasing of residual SO2 content. The potential transformation mechanisms could be due to the hydrolysis of polysaccharides. The research outcomes could provide a chemical basis for the safety and efficacy evaluations of sulfur-fumigated AMR.

Exploring the nephrotoxicity of sulfur-containing derivatives in sulfur-fumigated Panacis Quinquefolii Radix based on chemical profiling and untargeted metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Panacis Quinquefolii Radix (PQR) is often illegally sulfur fumigated to extend shelf life and improve appearance, but existing regulations of detecting SO2 residues do not accurately identify desulfurized sulfur-fumigated PQR (SF-PQR). Although sulfur-containing derivatives (SCDs) have been reported in some sulfur-fumigated herbs, there is a lack of research on the generation mechanisms and toxicity of SCDs. Our previous study reported the nephrotoxicity of SF-PQR, and there is an urgent necessity to illuminate the mechanism of toxicity as well as its association with SCDs. AIM OF THE STUDY: To investigate the transformation pattern of chemical components and SCDs in SF-PQR, and to disclose the linkage between SCDs and SF-PQR nephrotoxicity. MATERIALS AND METHODS: The extracts of PQR (before and after SF) were detected by the UPLC-LTQ-Orbitrap-MS method, and SCDs were screened as quality markers (Q-markers). The composition of sulfur combustion products was examined by ion chromatography to exploit the conversion mechanism of SCDs. After administration of PQR extracts to mice for two weeks, serum was collected for GC-MS-based untargeted metabolomics study to mine for differential metabolites. The upstream genes were traced by network analysis to probe toxicity targets. Molecular docking was used to uncover the interactions between SCDs and the targets. RESULTS: Thirty-three compounds were identified and 11 SCDs of saponins were screened, including four SO3 sulfonation products and five H2SO3 sulfonation products. Metabolomics study showed significant alterations in serum biochemistry of SF-PQR group, with substantial increases in fumarate and 2-heptanone content, and induced disturbances in glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis in mice. Network analysis revealed that the key toxicity targets were DECR1, PLA2G1B, and CAT. Molecular docking indicated that SCDs had stable interaction forces with the above three toxicity targets. CONCLUSION: SF-PQR caused kidney damage by affecting glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Eleven SCDs were potential nephrotoxic substances and Q-markers for identifying SF-PQR. This study is the first to systematically elucidate the mechanism of SF-PQR-related nephrotoxicity, providing a robust basis for the construction of new quality control standards and a global prohibition of sulfur fumigation.

Trimetallic Chalcogenide Species: Synthesis, Structures, and Bonding.

In an attempt to isolate boron-containing tri-niobium polychalcogenide species, we have carried out prolonged thermolysis reactions of [Cp*NbCl4] (Cp* = ɳ5-C5Me5) with four equivalents of Li[BH2E3] (E = Se or S). In the case of the heavier chalcogen (Se), the reaction led to the isolation of the tri-niobium cubane-like cluster [(NbCp*)3(µ3-Se)3(BH)(µ-Se)3] (1) and the homocubane-like cluster [(NbCp*)3(µ3-Se)3(µ-Se)3(BH)(µ-Se)] (2). Interestingly, the tri-niobium framework of 1 stabilizes a selenaborate {Se3BH}- ligand. A selenium atom is further introduced between boron and one of the selenium atoms of 1 to yield cluster 2. On the other hand, the reaction with the sulfur-containing borate adduct [LiBH2S3] afforded the trimetallic clusters [(NbCp*)3(µ-S)4{µ-S2(BH)}] (3) and [(NbCp*)3(µ-S)4{µ-S2(S)}] (4). Both clusters 3 and 4 have an Nb3S6 core, which further stabilizes {BH} and mono-sulfur units, respectively, through bi-chalcogen coordination. All of these species were characterized by 11B{1H}, 1H, and 13C{1H} NMR spectroscopy, mass spectrometry, infrared (IR) spectroscopy, and single-crystal X-ray crystallography. Moreover, theoretical investigations revealed that the triangular Nb3 framework is aromatic in nature and plays a vital role in the stabilization of the borate, borane, and chalcogen units.

Syntheses, and Structural and Physical Properties of Axially Chiral Biaryl Dicarboxylic Acids Bearing Chalcogen Atoms.

The preparation, optical resolution, and structural investigations of a series of axially chiral biaryl dicarboxylic acids bearing oxygen, sulfur, and selenium atoms were carried out. The crystal structures of sulfur- and selenium-containing derivatives revealed that the carboxy groups of these compounds are located in a co-planar geometry with the fused aromatic rings including the chalcogen atoms. These conformational controls were found to be achieved by chalcogen-bonding interactions between chalcogen atoms in the aromatic rings and oxygen atoms in the carboxy groups. Even in the case of a binaphthofuran derivative, in which the formation of chalcogen-bonding interactions was expected to be negligible, the carboxy groups were also found to be located in a co-planar geometry toward its fused cyclic rings. Natural bond orbital (NBO) analyses of these dicarboxylic acids indicated the formation not only for the chalcogen-bonding interactions for S and Se derivatives, but also the tetrel-bonding interactions between the oxygen atoms in the carboxy groups and the carbon atoms in the fused cyclic rings for all biaryl dicarboxylic acids. These tetrel-bonding interactions were thought to contribute to conformational control in the binaphthofuran derivative. Physical and chiroptical properties such as the racemization barriers and circular dichroism (CD) spectra of these biaryl dicarboxylic acids were also revealed.

Effects of sulfur-fumigated ginseng on the global quality of Si-Jun-Zi decoction, a traditional ginseng-containing multi-herb prescription, evaluated by metabolomics and glycomics strategies.

Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO2) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides, changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO2 residue in sulfur-fumigated ginseng, it couldn't recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs.

[Rapid identification of raw and sulfur-fumigated Paeoniae Radix Alba based on Heracles NEO ultra-fast gas phase electronic nose].

Since the current identification method for Paeoniae Radix Alba is complex in operation and long time-consuming with high requirements for technicians, the present study employed Heracles NEO ultra-fast gas phase electronic nose(E-nose) technology to identify raw and sulfur-fumigated Paeoniae Radix Alba decoction pieces in order to establish a rapid identification method for sulfur-fumigated Paeoniae Radix Alba. The odors of raw Paeoniae Radix Alba and its sulfur-fumigated products were analyzed by Heracles NEO ultra-fast gas phase E-nose to obtain the odor chromatographic information. The chemometric model was established, and the data were processed by principal component analysis(PCA), discriminant function analysis(DFA), soft independent modeling of class analogy(SIMCA), and partial least squares discriminant analysis(PLS-DA). The differential compounds of raw and sulfur-fumigated samples were qualitatively analyzed based on the Kovats retention index and Arochembase. As revealed by the comparison of gas chromatograms of raw and sulfur-fumigated Paeoniae Radix Alba, the heights of several peaks in the chromatograms before and after sulfur fumigation changed significantly. The peak(No.8) produced by ethylbenzene disappeared completely due to sulfonation reaction in the process of sulfur fumigation, indicating that ethylbenzene may be the key component in the identification of Paeoniae Radix Alba and its sulfur-fumigated products. In PCA, DFA, SIMCA, and PLS-DA models, the two types of samples were separated into two different regions, indicating that the established models can clearly distinguish between raw and sulfur-fumigated Paeoniae Radix Alba. The results showed that Heracles NEO ultra-fast gas phase E-nose technology could realize the rapid identification of raw and sulfur-fumigated Paeoniae Radix Alba, which provides a new method and idea for the rapid identification of sulfur-fumigated Chinese medicine.

Effects and contributory factors of sulfur-fumigation on the efficacy and safety of medicinal herbs evaluated by meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation undoubtedly alters the chemical and metabolic profiles, but controversially affects the efficacy and safety of medicinal herbs. AIM OF THE STUDY: To comprehensively evaluate the effects of sulfur-fumigation on the efficacy and safety of medicinal herbs using a meta-analysis approach and further investigate the potential contributory factors. MATERIALS AND METHODS: Literatures were retrieved on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang, and the outcomes involved activities and toxicities were extracted using standard data extraction forms. The effects of sulfur-fumigation on the efficacy and safety of medicinal herbs were evaluated by meta-analysis approaches. RESULTS: A total of sixteen studies were included in this study. Sulfur-fumigation reduced the efficacies of medicinal herbs with immune activity [thymus index (SMD = -1.81; P < 0.00001); spleen index (SMD = -1.11; P < 0.0001)], anti-oxidative activity [MDA (SMD = 2.60; P = 0.04); SOD (SMD = -2.21; P < 0.00001)], analgesic activity [heat tolerate time (SMD = -2.51; P = 0.001); writhing time (SMD = 0.36; P = 0.006)], anti-platelet aggregation activity (SMD = -1.84; P = 0.001), and anti-inflammatory activity [ear swelling degree (SMD = 0.47; P = 0.006)]. The reductions might be ascribed to sulfur-fumigation significantly reduced the contents of active ingredients in medicinal herbs, leading to dramatic decrease in the absorption of these ingredients and their metabolites in vivo. Furthermore, sulfur-fumigation induced the toxicities of medicinal herbs, mainly on hepatotoxicity, which might due to fumigation-induced residues of sulfur dioxide and heavy metal, and generations of sulfur-containing derivatives and toxic metabolites. Besides, administrated with sulfur-fumigated medicinal herbs with high sulfur ratio and/or higher dosage showed more significant toxicity. CONCLUSION: Sulfur-fumigation reduced the efficacy and safety of medicinal herbs, indicating sulfur-fumigation might not a feasible approach to process medicinal herbs. However, with obvious limitations, much more rigorous designed-trials are still needed to confirm the conclusion.

Cross-Talks Between Sulfane Sulfur and Thiol at a Zinc(II) Site.

Transformations of sulfane sulfur compounds (e. g. organic polysulfides (R-Sn -R, n>2) and elemental sulfur (S8 )) play pivotal roles in the biochemical landscape of sulfur, and thus supports signaling activities of H2 S. Although a number of previous reports illustrate amine mediated reactions of S8 and thiol (RSH) yielding R-Sn -R, this report illustrates that a tripodal [ZnII ] complex [(Bn3 Tren)ZnII -OH2 ](ClO4 )2 (1) facilitates the reactions of sulfane sulfur and thiol (RSH), thereby offering an amine-free biologically relevant complementary route. UV-vis monitoring of the reactions and a set of control experiments underline the definitive role of [ZnII ] coordination motif in the reactions of sulfane sulfur (e. g. S8 and R-Sn -R) with RSH. Detailed investigations (UV-vis, NMR, ESI-MS, intermediate trapping, and TEMPO radical interference experiments) disclose the key differences in the [ZnII ] versus previously known amine mediated routes. Moreover, the persulfide (RSS- ) trapping experiments using 1-fluoro-2,4-dinitrobenzene (F-DNB) reveal the intermediacy of RSS- species in the [ZnII ] mediated reactions of sulfane sulfur and thiol, thereby demonstrating [ZnII ] assisted persulfidation of thiol in the presence of sulfane sulfur species. Of broader impact, this study underscores the feasible influence of biologically relevant [ZnII ] coordination motifs (e. g. carbonic anhydrase) on the sulfane sulfur chemistry in biology.

77Se-13C based dipolar correlation experiments to map selenium sites in microcrystalline proteins.

Sulfur-containing sites in proteins are of great importance for both protein structure and function, including enzymatic catalysis, signaling pathways, and recognition of ligands and protein partners. Selenium-77 is an NMR active spin-1/2 nucleus that shares many physiochemical properties with sulfur and can be readily introduced into proteins at sulfur sites without significant perturbations to the protein structure. The sulfur-containing amino acid methionine is commonly found at protein-protein or protein-ligand binding sites. Its selenium-containing counterpart, selenomethionine, has a broad chemical shift dispersion useful for NMR-based studies of complex systems. Methods such as (1H)-77Se-13C double cross polarization or {77Se}-13C REDOR could be valuable to map the local environment around selenium sites in proteins but have not been demonstrated to date. In this work, we explore these dipolar transfer mechanisms for structural characterization of the GB1 V39SeM variant of the model protein GB1 and demonstrate that 77Se-13C based correlations can be used to map the local environment around selenium sites in proteins. We have found that the general detection limit is ~ 5 Å, but longer range distances up to ~ 7 Å can be observed as well. This study establishes a framework for the future characterization of selenium sites at protein-protein or protein-ligand binding interfaces.

[Design Strategy of Biologically Active Compounds Using Various Elements].

Almost all conventional drug discovery research has been based on hydrocarbon-based frameworks and common chemical elements such as nitrogen, oxygen, sulfur, and the halogens. However, triggered by the approval of bortezomib, a boronic acid-containing pharmaceutical agent, the incorporation of functionalities that are not native in biological systems has been intensively investigated. Several other boron-containing pharmaceuticals have also been marketed. Therefore, the inclusion of various elements is one of the most promising strategies for the development of novel and distinctive drug candidates. In this symposium review, the author focused on the 'elements chemistry' approaches for the structural development of biologically active compounds, particularly those involving silicon and phosphorus. The isosteric exchange of Si and C (Si/C-exchange) is one of the most-investigated forms of substituting elements. We revealed the detailed physicochemical impact of Si/C-exchange, and we proposed several applications of silyl functionalities other than the simple Si/C-exchange. Regarding phosphorus, we recently revealed that the P-B substructure can function as the isostere of C-C or Si-C substructures. In addition to these isosteric exchanges, the development of biologically active compounds bearing unique substructures such as carboranes, hydrophobic boron clusters, and ferrocene is introduced. These novel strategies provide several options for structural development, offering great potential for expanding the chemical space of medicinal chemistry.

Role of Sulphur and Heavier Chalcogens on the Antioxidant Power and Bioactivity of Natural Phenolic Compounds.

The activity of natural phenols is primarily associated to their antioxidant potential, but is ultimately expressed in a variety of biological effects. Molecular scaffold manipulation of this large variety of compounds is a currently pursued approach to boost or modulate their properties. Insertion of S/Se/Te containing substituents on phenols may increase/decrease their H-donor/acceptor ability by electronic and stereo-electronic effects related to the site of substitution and geometrical constrains. Oxygen to sulphur/selenium isosteric replacement in resveratrol or ferulic acid leads to an increase in the radical scavenging activity with respect to the parent phenol. Several chalcogen-substituted phenols inspired by Vitamin E and flavonoids have been prepared, which in some cases prove to be chain-breaking antioxidants, far better than the natural counterparts. Conjugation of catechols with biological thiols (cysteine, glutathione, dihydrolipoic acid) is easily achieved by addition to the corresponding ortho-quinones. Noticeable examples of compounds with potentiated antioxidant activities are the human metabolite 5-S-cysteinyldopa, with high iron-induced lipid peroxidation inhibitory activity, due to strong iron (III) binding, 5-S-glutathionylpiceatannol a most effective inhibitor of nitrosation processes, and 5-S-lipoylhydroxytyrosol, and its polysulfides that proved valuable oxidative-stress protective agents in various cellular models. Different methodologies have been used for evaluation of the antioxidant power of these compounds against the parent compounds. These include kinetics of inhibition of lipid peroxidation alkylperoxyl radicals, common chemical assays of radical scavenging, inhibition of the OH• mediated hydroxylation/oxidation of model systems, ferric- or copper-reducing power, scavenging of nitrosating species. In addition, computational methods allowed researchers to determine the Bond Dissociation Enthalpy values of the OH groups of chalcogen modified phenolics and predict the best performing derivative. Finally, the activity of Se and Te containing compounds as mimic of glutathione peroxidase has been evaluated, together with other biological activities including anticancer action and (neuro)protective effects in various cellular models. These and other achievements are discussed and rationalized to guide future development in the field.

Multifunctional MnO2/Ag3SbS3 Nanotheranostic Agent for Single-Laser-Triggered Tumor Synergistic Therapy in the NIR-II Biowindow.

Regulating the level of reactive oxygen species (ROS) in a tumor is an efficient and innovative anticancer strategy. However, the therapeutic efficacy of ROS-based therapies, such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), offers finite outcomes due to the oxygen dependence and limited concentration of hydrogen peroxide (H2O2) and overexpression of glutathione (GSH) within the tumor microenvironment (TME), so a single therapeutic strategy is insufficient to completely eliminate tumors. Therefore, we demonstrated an omnipotent nanoplatform MnO2/Ag3SbS3 (abbreviated as MA) with strong optical absorbance in the NIR-II biowindow and oxygen self-sufficient ROS-mediated ability, which not only relieves tumor hypoxia significantly but also enhances the photothermal therapy (PTT)/PDT/CDT efficacy. By 1064 nm laser irradiation, MnO2/Ag3SbS3 nanoparticles (NPs) reveal a favorable photothermal conversion efficiency of 23.15% and achieve a single-laser-triggered NIR-II PTT/PDT effect, resulting in effective tumor elimination. Once internalized into the tumor, MnO2/Ag3SbS3 NPs will be degraded to Mn2+ and Ag3SbS3. The released Ag3SbS3 NPs as a NIR-II phototherapy agent could be utilized for photoacoustic imaging-guided NIR-II PDT/PTT. Mn2+ could be used as a Fenton-like catalyst to continuously catalyze endogenous H2O2 for generating highly virulent hydroxyl radicals (•OH) for CDT and O2 for PDT, enhancing the efficiency of PDT and CDT, respectively. Meanwhile, Mn2+ realizes magnetic resonance imaging-guided accurate tumor therapy. Moreover, the MnO2/Ag3SbS3 NPs could deplete intracellular GSH in TME to promote oxidative stress of the tumor, further strengthening ROS-mediated antitumor treatment efficacy. Overall, this work presents a distinctive paradigm of TME-responsive PDT/CDT/PTT in the second near-infrared biowindow by depleting GSH and decomposing H2O2 for efficient and precise cancer treatment.

Biogenic Sulfur-Based Chalcogenide Nanocrystals: Methods of Fabrication, Mechanistic Aspects, and Bio-Applications.

Bio-nanotechnology has emerged as an efficient and competitive methodology for the production of added-value nanomaterials (NMs). This review article gathers knowledge gleaned from the literature regarding the biosynthesis of sulfur-based chalcogenide nanoparticles (S-NPs), such as CdS, ZnS and PbS NPs, using various biological resources, namely bacteria, fungi including yeast, algae, plant extracts, single biomolecules, and viruses. In addition, this work sheds light onto the hypothetical mechanistic aspects, and discusses the impact of varying the experimental parameters, such as the employed bio-entity, time, pH, and biomass concentration, on the obtained S-NPs and, consequently, on their properties. Furthermore, various bio-applications of these NMs are described. Finally, key elements regarding the whole process are summed up and some hints are provided to overcome encountered bottlenecks towards the improved and scalable production of biogenic S-NPs.