Hydrogen atom transfer (HAT) underlies free-radical chain-breaking by phenolic compounds. Using linear free energy relationship (LFER) analysis, proton transfer kinetics was hypothesized as a surrogate rate process for HAT. Phenol red is a probe that is easily oxidized to highly absorbing specie by hydroxyl ion. Absorbance decay of oxidized phenol red was induced by incremental proton transfer from a model phenolic (resorcinol). Global best-fit kinetics profile of resorcinol approximates a mono-exponential decay model (R 2 = 0.991) as a limiting law. Proton transfer rate constant (K ptt ) versus concentration reveal the utility of the slope (α aoc ) of the linear plot (r 2 = 0.990) as a sensitive predictor of phenolic antioxidant capacity. Superior antioxidant capacity profile of a polyphenol-rich dietary supplement: Garcinia kola seed extract, optimally obeyed a mixed linear/mono-exponential decay equation. Model robustness and selectivity for phenolics was achieved by specifying mathematical constraints as acceptance criteria. The method is more biologically relevant for chain-breaking antioxidants than free-radical-based assays because it captures antioxidant structure-function relationships. Further validation studies, using structurally diverse polyphenols, are warranted to ascertain general utility of the kinetic assay for achieving quality by design (QbD) in phenolic dietary supplement products.

Mechanosynthesis and solvent – based syntheses of transition metals (Ni, Co and Zn) complexes of Sodium diclofenac has been carried out by 1:1 molar ratio of the ligand to metal salts respectively. The synthesis of the metal complexes were confirmed by melting point determination, FT-IR (Fourier Transform Infra-red) and UV-visible spectroscopies. The ligand showed bidentate coordination to the metal ions through carboxylate moiety. Octahedral geometry was proposed for all the metal complexes. The antioxidant property of metal complexes was determined using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay with Ascorbic acid as control. The antioxidant evaluation results revealed that the synthesized metal complexes are promising antioxidant agents.

Polypharmacological activities of the biflavonoid fraction of Garcinia kola seed justify its development as a nutraceutical, however, quality assurance of active nutraceutical ingredient (ANI) requires conformance to appropriate standards of composition and quality. It was hypothesized that variation in extraction protocols, as previously reported for the biflavonoid fraction, would lead to variation in extract composition and potency. Computational antioxidant capacity simulation (CAOCS) assay of G. kola extracts obtained by different extraction protocols tested the hypothesis, through incremental addition (250 and 100 µL) of standard antioxidant (AOX) extract solutions in a photometric titration. Preferred model fitting was then statistically selected between mono-and bi-exponential decay. Bestfit reaction constant (k ptt ) was integrated into a metric for ranking antioxidant capacity (AOC) of the extracts. The AOC metric is a molecular descriptor for kinetics of phenolic bond cleavage. Three AOX extracts, namely, ethyl acetate seed extract, kolaviron and acetone seed extract were found to vary in composition, and produced optimal AOC values of 1500/g, 1150/g, and 1050/g respectively. Our findings demonstrated that the composition and potency of biflavonoid fraction of G. kola seed are critically dependent on solvent extraction protocol, and hence, consistent with the hypothesis. CAOCS assay is a suitable analytical tool for ensuring batch-to-batch sameness of ANI prepared from G. kola seed.

BackgroundLipophilicity is a crucial physicochemical parameter that predicts in vivo pharmacokinetics and should be reliably estimated in early stage drug discovery to reduce incidence of attrition. Previous methodologies for its measurement often lead to technically incorrect decisions due to simplistic architecture and poor biomimetic attributes. Significantly, a certain seed oil, used for biomembrane modelling on planar chromatographic platform, was reported to be sufficiently biomimetic and fit for purpose.ObjectivesTo evaluate olive oil (OL) and olive-castor oil (OL-C) equi-mixture as lipids for biomembrane simulation on planar chromatographic platform.Material and MethodRetention behavior of nabumetone, a model compound was used to optimize these potential lipid membranes using a thin film engineered from 5% Liquid paraffin (LP) as benchmark, while halofantrine, nabumetone , α-naphthol and β-naphthol representing varying molecular polarities, were used for validation studies. The validation involved 2-way analysis of variance (ANOVA) associated with variability in Basic lipophilicity parameter (Rmw), and Specific hydrophobic surface area (SHSA) for the optimized surfaces, relative to LP and octadecylsilane (ODS) Further validation entailed correlation of the lipophilicity descriptor i.e. isocratic chromatographic hydrophobicity index (ICHI) on OL, OL-C, ODS and LP with experimental Log P(octanol/water).ResultsOptimized film thicknesses were produced by 5% OL and 1.25% OL-C (p > 0.05). The 2-way ANOVA revealed great variability in performance characteristics of the surfaces (p < 0.0001), and the new surfaces also gave poorer correlation with Log P values (R2= 0.502 and 0.449 respectively).ConclusionThe 1.25 % OL-C demonstrated a higher biomimetic attribute and warrants further validation studies to ascertain biorelevance, of lipophilicity measurement on this platform, in predicting oral drug absorption. Keywords: Lipophilicity, Reversed-phase Thin Layer Chromatography, Retention behaviour, Olive oil, Castor oil

There is an urgent need for a biorelevant antioxidant capacity assay, which is crucial to quality-assured polyphenol dietary supplements. We hypothesize that the 'position', more than the 'number' of phenolic groups, is critical to the antioxidant capacity of polyphenols. Computational Antioxidant Capacity Simulation (CAOCS) assay was implemented to test the hypothesis, while refinement of existing assay protocol was aimed at reducing the cost of analysis. The antioxidant capacities of resorcinol, catechol and hydroquinone (3 diphenol positional isomers) were determined by CAOCS assay. Photometric titration experiments and associated informatics that constitute CAOCS assay were evaluated through the use of small increments (< 1 mL) of antioxidant solution. Antioxidant capacity ranking of the positional isomers was found to be; hydroquinone > catechol > resorcinol, (60/g, 46/g and 28/g respectively). The relative bond strength of the phenolic groups, which governs the ranking, was accounted for by structural theory. Optimal 250 µL increment of antioxidant solution afforded a 75% reduction of the amount of antioxidant required in the original assay protocol, where a 1 mL increment was used. CAOCS values vary widely for the positional isomers. The unique structure-antioxidant capacity-correlation (SACC) which confirmed our hypothesis is a signature of biorelevance. Significantly, microliter increments reduced the amount of active material required and hence, the cost of analysis. The methodology is thus attractive for profiling exotic and more expensive polyphenols. CAOCS assay holds a great promise of enabling quality-by-design (QbD) of polyphenol dietary supplements.