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Chemosphere Sep 2021Organosilicon compounds have numerous applications in consumer products. After entering the environment most of them are resistant against microbial degradation and they...
Organosilicon compounds have numerous applications in consumer products. After entering the environment most of them are resistant against microbial degradation and they persist in the environment. Accordingly, they are ubiquitously present in the environment. Therefore, better environmentally degradable organosilicon compounds are urgently needed. A systematic investigation of environmental degradability of organosilicon compounds allows to derive some general design principles, which in turn would enable chemists to reduce or better avoid environmental persistence of organosilicon compounds in the environment. Therefore, in this study, all organosilicon substances registered in the European Chemicals Agency (ECHA) database were evaluated for their environmental biodegradability. Results of own experiments with different organosilicon substances were added to extend the data basis. A dataset was generated. An assessment of all data was done and invalid data were excluded. The remaining 182 substances were grouped regarding their structure to derive general rules for the environmental biodegradability of organosilicon compounds. Non-biodegradable at all were for example cyclic, linear and branched siloxanes. Groups like ethers, esters, oximes, amines, and amides were prone to hydrolysis, which can result in readily biodegradable intermediates if they do not contain silicon functional groups anymore. This knowledge could be used for the design of better degradable organosilicon compounds as non-degradable substances should be avoided if they enter the environment after their usage.
Topics: Biodegradation, Environmental; Hydrolysis; Organosilicon Compounds; Silicon; Siloxanes
PubMed: 33887595
DOI: 10.1016/j.chemosphere.2021.130442 -
The Journal of Organic Chemistry Feb 2021We report solution structures of sodium hexamethyldisilazide (NaHMDS) solvated by >30 standard solvents (ligands). These include: toluene, benzene, and styrene;...
We report solution structures of sodium hexamethyldisilazide (NaHMDS) solvated by >30 standard solvents (ligands). These include: toluene, benzene, and styrene; triethylamine and related trialkylamines; pyrrolidine as a representative dialkylamine; dialkylethers including THF, -butylmethyl ether, and diethyl ether; dipolar ligands such as DMF, HMPA, DMSO, and DMPU; a bifunctional dipolar ligand nonamethylimidodiphosphoramide (NIPA); polyamines ,,,'-tetramethylenediamine (TMEDA), ,,,,″-pentamethyldiethylenetriamine (PMDTA), ,,,'-tetramethylcyclohexanediamine (TMCDA), and 2,2'-bipyridine; polyethers 12-crown-4, 15-crown-5, 18-crown-6, and diglyme; 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane ([2.2.2] cryptand); and tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1). Combinations of H, C, N, and Si NMR spectroscopies, the method of continuous variations, X-ray crystallography, and density functional theory (DFT) computations reveal ligand-modulated aggregation to give mixtures of dimers, monomers, triple ions, and ion pairs. N-Si coupling constants distinguish dimers and monomers. Solvation numbers are determined by a combination of solvent titrations, observed free and bound solvent in the slow exchange limit, and DFT computations. The relative abilities of solvents to compete in binary mixtures often match that predicted by conventional wisdom but with some exceptions and evidence of both competitive and cooperative (mixed) solvation. Crystal structures of a NaHMDS cryptate ion pair and a 15-crown-5-solvated monomer are included. Results are compared with those for lithium hexamethyldisilazide, lithium diisopropylamide, and sodium diisopropylamide.
Topics: Ligands; Molecular Structure; Organosilicon Compounds; Solvents
PubMed: 33471993
DOI: 10.1021/acs.joc.0c02546 -
Neoplasia (New York, N.Y.) Dec 2021A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is...
A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is imperative to discover effective therapies to overcome drug resistance and improve clinical outcomes. We have developed a novel class of silicon-containing compounds and evaluated the anticancer activities and mechanism of action using cellular and animal models of drug-resistant PCa. Five organosilicon compounds were evaluated for their anticancer activities in the NCI-60 panel and established drug-resistant PCa cell lines. GH1504 exhibited potent in vitro cytotoxicity in a broad spectrum of human cancer cells, including PCa cells refractory to ADT and chemotherapy. Molecular studies identified several potential targets of GH1504, most notably androgen receptor (AR), AR variant 7 (AR-v7) and survivin. Mechanistically, GH1504 may promote the protein turnover of AR, AR-v7 and survivin, thereby inducing apoptosis in ADT-resistant and chemoresistant PCa cells. Animal studies demonstrated that GH1504 effectively inhibited the in vivo growth of ADT-resistant CWR22Rv1 and chemoresistant C4-2B-TaxR xenografts in subcutaneous and intraosseous models. These preclinical results indicated that GH1504 is a promising lead that can be further developed as a novel therapy for drug-resistant PCa.
Topics: Animals; Antineoplastic Agents; Cell Line; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Male; Mice; Organosilicon Compounds; Prostatic Neoplasms, Castration-Resistant; Xenograft Model Antitumor Assays
PubMed: 34781084
DOI: 10.1016/j.neo.2021.11.006 -
Plant silicon-cell wall complexes: Identification, model of covalent bond formation and biofunction.Plant Physiology and Biochemistry : PPB Oct 2020Silicon (Si) is the second most abundant element on earth crust, consisting primarily of silicate minerals. Si is found in the tissues of almost all terrestrial plants... (Review)
Review
Silicon (Si) is the second most abundant element on earth crust, consisting primarily of silicate minerals. Si is found in the tissues of almost all terrestrial plants and is mostly deposited in specialized cells or cell walls as amorphous silica. Numerous discoveries have shown that in addition to non-covalent interactions through amorphous silica, Si can form covalent bonds with plant cell wall components such as hemicelluloses, pectin and lignin. The covalent bonds may be formed via Si-O-C linkages between monosilicic acid (HSiO) and cis-diols of cell wall polysaccharides or lignin. The covalently bound organosilicon, independent of amorphous inorganic silica, may play a crucial role in plant cell wall structure and remodeling and thus plant growth and its resistance against biotic and abiotic stresses. This review discusses the existing research on the discovery of plant silicon-cell wall complexes and proposes a model of their covalent bond formation and biofunction.
Topics: Cell Wall; Lignin; Organosilicon Compounds; Plant Cells; Plants; Polysaccharides; Silicon; Silicon Dioxide
PubMed: 32736240
DOI: 10.1016/j.plaphy.2020.07.020 -
Journal of Materials Chemistry. B Aug 2020Shape amphiphiles refer to a class of molecular conjugates composed by distinct building blocks with incommensurate shapes and chemical interactions. Whilst extensive...
Shape amphiphiles refer to a class of molecular conjugates composed by distinct building blocks with incommensurate shapes and chemical interactions. Whilst extensive efforts have been devoted to the solid state self-assembly and nanolithography applications of shape amphiphiles, only very limited examples of their usage in the biomedical field have been explored. In this work, we reported a series of gallic acid functionalized polyhedral oligomeric silsesquioxane (POSS)-based shape amphiphiles with various macromolecular architectures for efficient and accelerated wound healing. These antioxidant giant amphiphiles demonstrated good biocompatibility and strong free radical scavenging activity to prevent cell oxidative damage and then promote wound recovery. We describe these POSS-based antioxidant shape amphiphiles in an initial proof-of-concept study and propose that this family of functional giant amphiphiles will be useful in regenerative biomedicine.
Topics: Antioxidants; Gallic Acid; Humans; Hydrophobic and Hydrophilic Interactions; Materials Testing; Organosilicon Compounds; Oxidative Stress; Time Factors; Wound Healing
PubMed: 32667024
DOI: 10.1039/d0tb00578a -
ChemMedChem Dec 2015The GPR81 and GPR109A receptors mediate antilipolytic effects and are potential drug targets for the treatment of metabolic disorders such as dyslipidemia and type 2...
The GPR81 and GPR109A receptors mediate antilipolytic effects and are potential drug targets for the treatment of metabolic disorders such as dyslipidemia and type 2 diabetes. There is still a need to identify potent GPR81 agonists as pharmacological tools. A high-throughput screen identified an acylurea-based GPR81 agonist lead series, with activities at the GPR109A receptor as well. To expand the chemical scope and to explore the pharmacological and pharmacokinetic consequences, a series of structurally related organosilicon compounds with a 6-sila-4,5,6,7-tetrahydrobenzo[d]thiazole skeleton was synthesized and studied for their physicochemical properties [octanol/water distribution coefficient (pH 7.4), solubility in HBSS buffer (pH 7.4)], agonistic potency at rat GPR81 and GPR109A receptors, and intrinsic clearance in human liver microsomes and rat hepatocytes. The straightforward synthesis of these organosilicon compounds offered a valuable expansion of the chemical scope in the above-mentioned GPR81 agonist lead series, provided potency and efficacy SAR, and yielded compounds with sub-micromolar GPR81 potency. This work supports the value of including silicon chemistry into the toolbox of medicinal chemistry.
Topics: Animals; Benzothiazoles; Crystallography, X-Ray; Hepatocytes; Humans; Microsomes, Liver; Molecular Conformation; Organosilicon Compounds; Protein Binding; Rats; Receptors, G-Protein-Coupled; Receptors, Nicotinic; Solubility; Structure-Activity Relationship
PubMed: 26459194
DOI: 10.1002/cmdc.201500343 -
ChemPlusChem May 2020Photodynamic therapy is an alternative modality for the therapy of diseases such as cancer in a minimally invasive manner. The essential photosensitizer, which acts as a... (Review)
Review
Photodynamic therapy is an alternative modality for the therapy of diseases such as cancer in a minimally invasive manner. The essential photosensitizer, which acts as a catalyst when absorbing light, converts oxygen into cytotoxic reactive oxygen species that ablate malignant cells through apoptosis and/or necrosis, destroy tumor microvasculature, and stimulate immunity. An activatable photosensitizer whose photoactivity could be turned on by a specific disease biomarker is capable of distinguishing healthy cells from diseased cells, thereby reducing off-target photodamage. In this Minireview, we highlight progress in activatable organic photosensitizers over the past five years, including: (i) biorthogonal activatable BODIPYs; (ii) activatable Se-rhodamine with single-cell resolution; (iii) silicon phthalocyanine targeting oxygen tension; (iv) general D-π-A scaffolds; and (v) AIEgens. The potential challenges and opportunities for developing new types of activatable organic photosensitizers to overcome the hypoxia dilemmas of photodynamic therapy are discussed.
Topics: Apoptosis; Boron Compounds; Humans; Indoles; Light; Neoplasms; Organosilicon Compounds; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Rhodamines
PubMed: 32401421
DOI: 10.1002/cplu.202000203 -
Chemical Reviews Oct 2016Unnatural α-amino acids form a family of essential molecules used for, among other applications, the synthesis of modified peptides, to improve resistance to... (Review)
Review
Unnatural α-amino acids form a family of essential molecules used for, among other applications, the synthesis of modified peptides, to improve resistance to proteolytic enzyme degradation, and to modulate physico- and biochemical properties of bioactive peptides as well as chiral inducers in asymmetric synthesis. Among them, silicon-containing unnatural amino acids are becoming an interesting new class of building blocks. The replacement of carbon atoms in bioactive substances with silicon is becoming increasingly popular. Peptides containing silyl amino acids hold great promise for maintaining or reinforcing the biological activity of active compounds, while they simultaneously enhance their resistance to enzyme degradation. In addition, the lipophilicity of the silicon atom facilitates their membrane crossing and their bioavailability. Nowadays, the interest of the pharmaceutical industry in peptide- and protein-based therapies is increasing. In this respect, silicon-containing amino acids and peptides are likely to be a significant part of future innovations in this area, and more generally in the area of biomolecules. In this process, commercial availability of silicon-containing amino acids is necessary: new syntheses have been developed, and work in this area is ongoing. This review aims to be a comprehensive and general summary of the different methods used to prepare silicon-containing amino acids and their implications on conformational structures and biological applications when they are incorporated into bioactive molecules.
Topics: Amino Acids; Animals; Molecular Conformation; Organosilicon Compounds; Peptides; Stereoisomerism; Structure-Activity Relationship
PubMed: 27529497
DOI: 10.1021/acs.chemrev.6b00122 -
Journal of Biomedical Optics Apr 2015Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy....
Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy. Therefore, the design of stable phantoms is essential to achieve semiquantitative evaluation of the performance of a photoacoustic system and can help optimize the properties of contrast agents. We designed and developed a polydimethylsiloxane (PDMS) phantom with exceptionally fine geometry; the phantom was tested using photoacoustic experiments loaded with the standard indocyanine green dye and compared to an agar phantom pattern through polyethylene glycol-gold nanorods. The linearity of the photoacoustic signal with the nanoparticle number was assessed. The signal-tonoiseratio and contrast were employed as image quality parameters, and enhancements of up to 50 and up to 300%, respectively, were measured with the PDMS phantom with respect to the agar one. A tissue-mimicking (TM)-PDMS was prepared by adding TiO2 and India ink; photoacoustic tests were performed in order to compare the signal generated by the TM-PDMS and the biological tissue. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.
Topics: Equipment Design; Models, Cardiovascular; Organosilicon Compounds; Phantoms, Imaging; Photoacoustic Techniques
PubMed: 25894254
DOI: 10.1117/1.JBO.20.4.046008 -
Bioorganic Chemistry Feb 2021Cancer has become an important public problem in worldwide since cancer incidence and mortality are growing rapidly. In this study, water soluble and non-aggregated...
Design, synthesis and biological evaluation of water soluble and non-aggregated silicon phthalocyanines, naphthalocyanines against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines as potential anticancer agents.
Cancer has become an important public problem in worldwide since cancer incidence and mortality are growing rapidly. In this study, water soluble and non-aggregated silicon (IV) phthalocyanines and naphthalocyanines containing (3,5-bis{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy groups have been synthesized and characterized to investigate their anticancer potential. Their DNA binding/nuclease, topoisomerases inhibition were investigated using UV-Vis absorption, thermal denaturation and agarose gel electrophoresis. The in vitro cytotoxic properties of the compounds on human lung (A549), breast (BT-20), liver (SNU-398), prostate (DU-145), melanoma (SK-Mel 128) carcinoma and human fibroblast (HFC) normal cell lines were evaluated by using MTT assay. In order to determine the mechanism of cancer cell growth suppression, cell cycle analysis was carried out using flow cytometer on A549 cell line. The K values of SiPc1a and SiNc2a were 6.85 ± (0.35) × 10 and 1.72 ± (0.16) × 10 M and T values of ct-DNA were calculated as 82.02 °C and 78.07 °C, respectively in the presence of both compounds. The Δ values of SiPc1a and SiNc2a were calculated as 6.45 and 2.50 °C, respectively. The nuclease effects of SiPc1a and SiNc2a with supercoiled plasmid pBR322 DNA demonstrated that both compounds did not trigger any DNA nuclease effects at the lowest concentrations without irradiation whereas both compounds in the presence of activating agent (HO) showed significant plasmid DNA nuclease actions under irradiation (22.5 J/cm). SiPc1a and SiNc2a inhibited to topoisomerase I on increasing concentrations whilst they had lower inhibition action toward topoisomerase II that of topoisomerase I. The in vitro cytotoxicity studies displayed that SiPc1a had the highest cytotoxic effects among the tested compounds against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines with CC values ranged from 0.49 to 2.99 µM. Furthermore, SiPc1a inhibited cell proliferation by cell cycle arrest in G/G phase. All of these results suggested that SiPc1a is a promising candidate as an anticancer agent.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; DNA; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Deoxyribonucleases; Drug Design; G1 Phase Cell Cycle Checkpoints; Humans; Hydrogen Peroxide; Indoles; Organosilicon Compounds; Solubility; Topoisomerase I Inhibitors; Water
PubMed: 33454505
DOI: 10.1016/j.bioorg.2021.104637