Photochemical Electrocyclic Ring Closure and Leaving Group Expulsion from N-(9-oxothioxanthenyl)Benzothiophene Carboxamides

N-(9-Oxothioxanthenyl)benzothiophene carboxamides bearing leaving groups (LG− = Cl−, PhS−, HS−, PhCH2S−) at the C-3 position of the benzothiophene ring system photochemically cyclize with nearly quantitative release of the leaving group, LG−. The LG− photoexpulsions can be conducted with 390 nm light or with a sunlamp. Solubility in 75% aqueous CH3CN is achieved by introducing a carboxylate group at the C-6 position of the benzothiophene ring. The carboxylate and methyl ester derivatives regiospecifically cyclize at the more hindered C-1 position of the thioxanthone ring. Otherwise, the photocyclization favors the C-3 position of the thioxanthone. Quantum yields for reaction are 0.01–0.04, depending on LG− basicity. Electronic structure calculations for the triplet excited state show that excitation transfer occurs from the thioxanthone to the benzothiophene ring. Subsequent cyclization in the triplet excited state is energetically favourable and initially generates the triplet excited state of the zwitterionic species. Expulsion of LG− is thought to occur once this species converts to the closed shell ground state

No Longer a Complex, Not Yet a Molecule: A Challenging Case of Nitrosyl O-Hydroxide, HOON

N-(9-Oxothioxanthenyl)benzothiophene carboxamides bearing leaving groups (LG− = Cl−, PhS−, HS−, PhCH2S−) at the C-3 position of the benzothiophene ring system photochemically cyclize with nearly quantitative release of the leaving group, LG−. The LG− photoexpulsions can be conducted with 390 nm light or with a sunlamp. Solubility in 75% aqueous CH3CN is achieved by introducing a carboxylate group at the C-6 position of the benzothiophene ring. The carboxylate and methyl ester derivatives regiospecifically cyclize at the more hindered C-1 position of the thioxanthone ring. Otherwise, the photocyclization favors the C-3 position of the thioxanthone. Quantum yields for reaction are 0.01–0.04, depending on LG− basicity. Electronic structure calculations for the triplet excited state show that excitation transfer occurs from the thioxanthone to the benzothiophene ring. Subsequent cyclization in the triplet excited state is energetically favourable and initially generates the triplet excited state of the zwitterionic species. Expulsion of LG− is thought to occur once this species converts to the closed shell ground state

Preservation of Bovine Hide using Less Salt with Low Concentration of Antiseptic

Content: A Conventional technique of bovine hide preservation requires approximately 40-50% sodium chloride or table salt on raw hide weight or 95% saturated brine in case of wet salting. This salt resides in wastewater after the soaking process and generates a huge environmental pollution in the form of total dissolved solids (TDS) and chloride (Cl-) during leather processing. The current research has developed an antiseptic based hide curing formulation using 45% saturated brine solution which reduces 50% salt usage in compare to the traditional method. For hide preservation, it is essential to arrest microbial attack on hide as the main constituent of raw hide is protein which is very susceptible for bacterial degradation. The newly developed formulations have been found more effective in limiting microbial growth on cured hide than the conventional method preserving the bovine hide for more than 30 days. In-process analysis of cured hides during storage period reveals the compatibility of the alternative curing process. Post-leather analysis e.g. grain pattern, scanning electron microscopic images, mechanical properties and organoleptic evaluation reveal that the crust leather produced from alternatively cured hides are comparable to the control obtained from traditionally preserved hide. The efficacy of the alternative system is also assessed by monitoring the environmental impacts caused by the leather processing effluents on the basis of TDS and chloride content, total solids (TS), total aerobic bacterial counts in soaking liquor, Bio-Chemical oxygen demand (BOD) and Chemical oxygen demand (COD). The environmental advantages of the alternative hide curing method are determined particularly by 50% reduction of TDS and chloride content. Therefore, this new development will not only preserve hide through better protection from microorganisms but also offer improved conservation of the environment. Take-Away: Environmentally friendly technique of animal hide preservation Hide preservation through better protection from microbial degradatoin than the traditional techniqu

Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets

Background: Dual-specificity phosphatase-5 (DUSP5) plays a central role in vascular development and disease. We present a p-nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5. Methods: pNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds the DUSP5 phosphatase domain with a Km of 7.6 ± 0.4 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual-phosphorylated ERK2 substrate tripeptide (pThr-Glu-pTyr). Secondary assays were performed with full length DUSP5 with ERK2 as substrate. Results: The most potent inhibitor has a naphthalene trisulfonate (NTS) core. A search for similar compounds in a drug database identified suramin, a dimerized form of NTS. While suramin appears to be a potent and competitive inhibitor (25 ± 5 μM), binding to the DUSP5 phosphatase domain more tightly than the monomeric ligands of which it is comprised, it also aggregates. Further ligand-based screening, based on a pharmacophore derived from the 7 Å separation of sulfonates on inhibitors and on sulfates present in the DUSP5 crystal structure, identified a disulfonated and phenolic naphthalene inhibitor (CSD3 _2320) with IC50 of 33 μM that is similar to NTS and does not aggregate. Conclusions: The new DUSP5 inhibitors we identify in this study typically have sulfonates 7 Å apart, likely positioning them where the two phosphates of the substrate peptide (pThr-Glu-pTyr) bind, with one inhibitor also positioning a phenolic hydroxyl where the water nucleophile may reside. Polysulfonated aromatic compounds do not commonly appear in drugs and have a tendency to aggregate. One FDA-approved polysulfonated drug, suramin, inhibits DUSP5 and also aggregates. Docking and modeling studies presented herein identify polysulfonated aromatic inhibitors that do not aggregate, and provide insights to guide future design of mimics of the dual-phosphate loops of the ERK substrates for DUSPs. Keywords: DUSP5, Phosphatase, Drug discovery, Docking, Suramin, Vascular anomalie

Preservation of Bovine Hide using Less Salt with Low Concentration of Antiseptic

Content: A Conventional technique of bovine hide preservation requires approximately 40-50% sodium chloride or table salt on raw hide weight or 95% saturated brine in case of wet salting. This salt resides in wastewater after the soaking process and generates a huge environmental pollution in the form of total dissolved solids (TDS) and chloride (Cl-) during leather processing. The current research has developed an antiseptic based hide curing formulation using 45% saturated brine solution which reduces 50% salt usage in compare to the traditional method. For hide preservation, it is essential to arrest microbial attack on hide as the main constituent of raw hide is protein which is very susceptible for bacterial degradation. The newly developed formulations have been found more effective in limiting microbial growth on cured hide than the conventional method preserving the bovine hide for more than 30 days. In-process analysis of cured hides during storage period reveals the compatibility of the alternative curing process. Post-leather analysis e.g. grain pattern, scanning electron microscopic images, mechanical properties and organoleptic evaluation reveal that the crust leather produced from alternatively cured hides are comparable to the control obtained from traditionally preserved hide. The efficacy of the alternative system is also assessed by monitoring the environmental impacts caused by the leather processing effluents on the basis of TDS and chloride content, total solids (TS), total aerobic bacterial counts in soaking liquor, Bio-Chemical oxygen demand (BOD) and Chemical oxygen demand (COD). The environmental advantages of the alternative hide curing method are determined particularly by 50% reduction of TDS and chloride content. Therefore, this new development will not only preserve hide through better protection from microorganisms but also offer improved conservation of the environment. Take-Away: Environmentally friendly technique of animal hide preservation Hide preservation through better protection from microbial degradatoin than the traditional techniqu

Preservation of Bovine Hide using Less Salt with Low Concentration of Antiseptic

Content: A Conventional technique of bovine hide preservation requires approximately 40-50% sodium chloride or table salt on raw hide weight or 95% saturated brine in case of wet salting. This salt resides in wastewater after the soaking process and generates a huge environmental pollution in the form of total dissolved solids (TDS) and chloride (Cl-) during leather processing. The current research has developed an antiseptic based hide curing formulation using 45% saturated brine solution which reduces 50% salt usage in compare to the traditional method. For hide preservation, it is essential to arrest microbial attack on hide as the main constituent of raw hide is protein which is very susceptible for bacterial degradation. The newly developed formulations have been found more effective in limiting microbial growth on cured hide than the conventional method preserving the bovine hide for more than 30 days. In-process analysis of cured hides during storage period reveals the compatibility of the alternative curing process. Post-leather analysis e.g. grain pattern, scanning electron microscopic images, mechanical properties and organoleptic evaluation reveal that the crust leather produced from alternatively cured hides are comparable to the control obtained from traditionally preserved hide. The efficacy of the alternative system is also assessed by monitoring the environmental impacts caused by the leather processing effluents on the basis of TDS and chloride content, total solids (TS), total aerobic bacterial counts in soaking liquor, Bio-Chemical oxygen demand (BOD) and Chemical oxygen demand (COD). The environmental advantages of the alternative hide curing method are determined particularly by 50% reduction of TDS and chloride content. Therefore, this new development will not only preserve hide through better protection from microorganisms but also offer improved conservation of the environment. Take-Away: Environmentally friendly technique of animal hide preservation Hide preservation through better protection from microbial degradatoin than the traditional techniqu