Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1- 120 mM and 5.2-90 mM for RAB sodium and DOM, respectively while SWAdSV was 7.5-803107M and 5– 703107M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binarybinary mixture in synthetic mixtures and biological fluids.

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1- 120 mM and 5.2-90 mM for RAB sodium and DOM, respectively while SWAdSV was 7.5-803107M and 5– 703107M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binarybinary mixture in synthetic mixtures and biological fluids.

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1- 120 mM and 5.2-90 mM for RAB sodium and DOM, respectively while SWAdSV was 7.5-803107M and 5– 703107M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binarybinary mixture in synthetic mixtures and biological fluids.

Lipophilicity plays a crucial role in determining the hepato-selectivity and hence, the biological activity and the associated side effects of statins. Herein, the employment of RP-TLC for estimation of lipophilicity of six statins namely; atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and fluvastatin is examined. A very good correlation between the chromatographically-determined retention parameters (relative lipophilicity (RM0) or lipophilic parameter (C0)) and both experimental and computed log P values were obtained. However, the results indicate that the type of organic modifier in the mobile phase system (methanol, acetonitrile and acetone) has a small influence on RM0 or C0 values. Higher values of RM0 or C0 are ascribed to lipophilic statins and lower values of RM0 or C0 are attributed to hydrophilic ones. Therefore, RM0 or C0 could be effectively used as simple practical predictors of extra-hepatic distributions of statins and thus their expected side effects. Furthermore, three QSPR (quantitative structure-property relationship) models were constructed to describe the relationship between RM0 with log P and log D of the statins under investigation. These models can be very useful to predict the lipophilicity of other members of statin drugs and might be expanded to newly synthesized compounds with the same structural features.

Lipophilicity plays a crucial role in determining the hepato-selectivity and hence, the biological activity and the associated side effects of statins. Herein, the employment of RP-TLC for estimation of lipophilicity of six statins namely; atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and fluvastatin is examined. A very good correlation between the chromatographically-determined retention parameters (relative lipophilicity (RM0) or lipophilic parameter (C0)) and both experimental and computed log P values were obtained. However, the results indicate that the type of organic modifier in the mobile phase system (methanol, acetonitrile and acetone) has a small influence on RM0 or C0 values. Higher values of RM0 or C0 are ascribed to lipophilic statins and lower values of RM0 or C0 are attributed to hydrophilic ones. Therefore, RM0 or C0 could be effectively used as simple practical predictors of extra-hepatic distributions of statins and thus their expected side effects. Furthermore, three QSPR (quantitative structure-property relationship) models were constructed to describe the relationship between RM0 with log P and log D of the statins under investigation. These models can be very useful to predict the lipophilicity of other members of statin drugs and might be expanded to newly synthesized compounds with the same structural features.

Lipophilicity plays a crucial role in determining the hepato-selectivity and hence, the biological activity and the associated side effects of statins. Herein, the employment of RP-TLC for estimation of lipophilicity of six statins namely; atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and fluvastatin is examined. A very good correlation between the chromatographically-determined retention parameters (relative lipophilicity (RM0) or lipophilic parameter (C0)) and both experimental and computed log P values were obtained. However, the results indicate that the type of organic modifier in the mobile phase system (methanol, acetonitrile and acetone) has a small influence on RM0 or C0 values. Higher values of RM0 or C0 are ascribed to lipophilic statins and lower values of RM0 or C0 are attributed to hydrophilic ones. Therefore, RM0 or C0 could be effectively used as simple practical predictors of extra-hepatic distributions of statins and thus their expected side effects. Furthermore, three QSPR (quantitative structure-property relationship) models were constructed to describe the relationship between RM0 with log P and log D of the statins under investigation. These models can be very useful to predict the lipophilicity of other members of statin drugs and might be expanded to newly synthesized compounds with the same structural features.

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