Sayo O. Fakayode

Lanthanide Complexes as Fluorescent Indicators for Neutral Sugars and Cancer Diagnosis

Simple water-soluble lanthanum and europium complexes are effective at detecting neutral sugars as well as glycolipids and phospholipids. In solutions at physiologically relevant pH the fluorescent lanthanum complex binds neutral sugars with apparent binding constants comparable to those of arylboronic acids. Interference from commonly occurring anions is minimal. The europium complex detects sialic acid-containing gangliosides at pH 7.0 over an asialoganglioside. This selectivity is attributed, in large part, to the cooperative complexation of the oligosaccharide and sialic acid residues to the metal center, based on analogous prior studies. In MeOH, lysophosphatidic acid (LPA), a biomarker for several pathological conditions including ovarian cancer, is selectively detected by the europium complex. LPA is also detected via a fluorescence increase in human plasma samples. The 2-sn-OH moiety of LPA plays a key role in promoting binding to the metal center. Other molecules found in common brain ganglioside and phospholipid extracts do not interfere in the ganglioside or LPA fluorescence assays.

Determination of pharmacologically active compounds in root extracts of Cassia alata L. by use of high performance liquid chromatography

A simple high performance liquid chromatography (HPLC) method was developed and validated for the determination of six phenolic compounds, five anthraquinones (rhein, aloe-emodin, emodin, chrysophanol and physcion) and a flavonoid (kaempferol), in root extracts from Cassia alata L. Solid-phase extraction, using C(18) cartridges, was used to remove interfering substances from the root extracts. The extracts were analyzed on a C(18) column using an isocratic mobile phase which consisted of acetonitrile, methanol, and 10mM aqueous ammonium acetate (25:55:20, v/v). Identification of the analytes was performed by use of standards and on-line mass spectrometric detection using atmospheric pressure chemical ionization. The concentration of the phenolic compounds in the root extracts was determined using HPLC with ultraviolet detection at 260nm. The limits of detection obtained for the anlytes were in the range of 0.23-4.61ppm. The overall R.S.D. precision values (intra- and inter-day) for the retention times and peak-areas were lower than 0.16 and 2.10%, respectively. In addition, the recovery of the developed method for the analysis of these phenolic compounds was determined, and ranged from 81.2+/-4.3 to 106+/-2%.

Determination of the enantiomeric composition of some molecules of pharmaceutical interest by chemometric analysis of the UV spectra of guest–host complexes formed with modified cyclodextrins

Multivariate regression modeling techniques (PLS-1 regression modeling) were applied to ordinary UV spectral absorption data obtained on solutions containing inclusion complexes formed between homochiral modified cyclodextrins (methyl-beta-cyclodextrin, alpha-, beta-, and gamma-carboxymethyl cyclodextrins and alpha-, beta-, and gamma-hydroxypropyl cyclodextrins) and four guest molecules of pharmaceutical interest (ephedrine, norephedrine, norepinephrine-l-bitartrate, and tryptophan methyl ester). The PLS-1 regression models were developed by correlating the known enantiomeric composition of laboratory prepared samples with ordinary UV absorption spectral data. The regression models were subsequently validated with laboratory-prepared test sets. The rms percent relative error in the predicted mol fraction of (1S, 2R)-(+)-ephedrine, (1S, 2R)-(+)-norephedrine, (R)-(-)-norepinephrine-l-bitartrate, and d-tryptophan methyl ester obtained with the independently prepared test sets was heavily dependent on the host molecule used.

Controllable formation of ionic liquid micro- and nanoparticles via a melt-emulsion-quench approach.

We present a facile, scalable, and general method for the size-variable generation of monodispersed, near-spherical solid-state (frozen) ionic liquid nanoparticles based on a novel melt-emulsion-quench approach. Simple manipulation of the internal templating droplets within oil-in-water (o/w) microemulsions also permits the formation of well-defined microspheres. This simple and rapid preparation, requiring neither specialized equipment nor harsh conditions, suggests a wealth of potential for these designer nanomaterials within the biomedical, materials, and analytical communities.

Gold Nanoparticle Sensor for Homocysteine Thiolactone-Induced Protein Modification

Homocysteine thiolactone-induced protein modification (HTPM) is a unique post-translational protein modification that is recognized as an emergent biomarker for cardiovascular disease. HTPM involves the site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HTL) to produce protein homocystamide, which has been found at elevated levels in patients with coronary heart disease. Herein, we report the development of a novel gold nanoparticle (GNP) biochemical sensor for detection of protein homocystamide in an in vitro serum protein-based model system. Human serum albumin (HSA) and human sera were subjected to HTPM in vitro to produce HSA-homocystamide or serum protein homocystamide, respectively, which was subsequently treated with citrate-capped GNPs. This GNP sensor typically provided instantaneous visual confirmation of HTPM in the protein model systems. Transmission electron microscopy images of the GNPs in the presence of HSA-homocystamide suggest that modification-directed nanoparticle assembly is the mechanism by which the biochemical sensor produces a colorimetric signal. The resultant nanoparticle-protein assembly exhibited excellent thermal and dilutional stability, which is expected for a system stabilized by chemisorption and intermolecular disulfide bonding. The sensor typically provided a linear response for modified human sera concentrations greater than approximately 5 mg/mL. The calculated limit of detection and calibration sensitivity for the method in human sera were 5.2 mg/mL and 13.6 AU . (microg/mL)-1, respectively.

Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro

Hypoxia is a hallmark of solid tumors, including breast cancer, and the extent of tumor hypoxia is associated with treatment resistance and poor prognosis. Considering the limited treatment of hypoxic tumor cells and hence a poor prognosis of breast cancer, the investigation of natural products as potential chemopreventive anti-angiogenic agents is of paramount interest. Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the primary anthraquinone in the roots of Cassia alata L., is a naturally occurring quinone which exhibits a variety of biologic activities including anti-cancer activity. However, the effect of rhein on endothelial or cancer cells under hypoxic conditions has never been delineated. Therefore, the aim of this study was to investigate whether rhein inhibits angiogenesis and the viability of hormone-dependent (MCF-7) or -independent (MDA-MB-435s) breast cancer cells in vitro under normoxic or hypoxic conditions. Rhein inhibited vascular endothelial growth factor (VEGF(165))-stimulated human umbilical vein endothelial cell (HUVEC) tube formation, proliferation and migration under normoxic and hypoxic conditions. In addition, rhein inhibited in vitro angiogenesis by suppressing the activation of phosphatidylinositol 3-kinase (PI3K), phosphorylated-AKT (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) but showed no inhibitory effects on total AKT or ERK. Rhein dose-dependently inhibited the viability of MCF-7 and MDA-MB-435s breast cancer cells under normoxic or hypoxic conditions, and inhibited cell cycle in both cell lines. Furthermore, Western blotting demonstrated that rhein inhibited heat shock protein 90alpha (Hsp90α) activity to induce degradation of Hsp90 client proteins including nuclear factor-kappa B (NF-κB), COX-2, and HER-2. Rhein also inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF(165)), epidermal growth factor (EGF), and the phosphorylation of inhibitor of NF-κB (I-κB) under normoxic or hypoxic conditions. Taken together, these data indicate that rhein is a promising anti-angiogenic compound for breast cancer cell viability and growth. Therefore, further studies including in vivo and pre-clinical need to be performed.

Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml( - 1) TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 +/- 0.002 mg ml( - 1)) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 +/- 5.6% after 96 h.

Trace metal content and estimated daily human intake from chicken eggs in Ibadan, Nigeria.

A total of 151 chicken eggs and 4 local chicken feeds purchased directly from the poultry farms, at the local markets, and along the roadsides of Ibadan, Nigeria, were analyzed for lead, cadmium, copper, iron, nickel, zinc, and cobalt by carbon graphite atomic absorption spectrophotometry. The authors found strong, positive correlations between the levels of metals in the feeds and the corresponding levels of metals in the eggs. The overall average concentrations (mg/kg) of each metal in eggs were as follows: lead, 0.59; cadmium, 0.07; copper, 0.78; iron, 23.20; nickel, 0.03; zinc, 13.75; and cobalt, 0.01. The average estimated daily intake of lead, cadmium, copper, and iron per person was 19.5 μg, 2.4 μg, 25.6 μg, and 762.3 μg, respectively, whereas daily intakes of nickel, zinc, and cobalt were 0.9 μg, 452.1 μg, and 0.2 μg per person. The concentrations of some metals in eggs from this study did not differ appreciably from levels determined in eggs from other countries; concentrations of lead and cadmium in the current study, however, were comparatively greater than levels found in other countries. Therefore, the estimated daily intakes of lead and cadmium in this region slightly exceeded the normal reported daily intakes of lead and cadmium from eggs in some other countries.

Determination of the enantiomeric composition of phenylalanine samples by chemometric analysis of the fluorescence spectra of cyclodextrin guest–host complexes

A novel strategy for determining the enantiomeric composition of phenylalanine samples that combines ordinary fluorescence spectroscopy, guest-host cyclodextrin chemistry, and multivariate regression modeling is investigated. Partial-least-squares regression (PLS-1) models were developed from fluorescence spectral data obtained with a series of samples containing cyclodextrin guest-host complexes of phenylalanine with different known enantiomeric compositions. The regression models were subsequently validated by determining the enantiomeric composition of a set of independently prepared phenylalanine samples. The ability of the models to correctly predict the enantiomeric compositions of future samples was evaluated in terms of the root-mean-square percent relative error (RMS%RE). The RMS%RE in the mol fraction of D-phenylalanine ranged from 1.3% to 3.0% when beta-cyclodextrin was used as the host molecule for different guest-host concentrations. The RMS%RE in the mol fraction of D-phenylalanine obtained in a similar validation study conducted with gamma-cyclodextrin ranged between 1.8% and 4.0% for different guest-host concentrations. Compared with previous studies done in absorption, fluorescence data were found to be more sensitive and the spectral differences observed as a function of enantiomeric composition were more uniformly spaced, making regression modeling more reliable. As a result, good regression models could be made at lower concentrations than were possible previously when absorption measurements were used.

Fluorescence, Phosphorescence, and Chemiluminescence

Noureen Siraj,† Bilal El-Zahab,‡ Suzana Hamdan,† Tony E. Karam,† Louis H. Haber,† Min Li, Sayo O. Fakayode, Susmita Das, Bertha Valle, Robert M. Strongin, Gabor Patonay, Herman O. Sintim, Gary A. Baker, Aleeta Powe, Mark Lowry, Jan O. Karolin, Chris D. Geddes, and Isiah M. Warner*,† †Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States ‡Department of Mechanical and Materials Engineering, Florida International University, Miami, Florida 33174, United States Process Development Center, Albemarle Corporation, Baton Rouge, Louisiana 70805, United States Department of Chemistry, Winston-Salem State University, Winston-Salem, North Carolina 27110, United States Department of Civil Engineering, Adamas Institute of Technology, Barasat, Kolkata 700126, West Bengal India Department of Chemistry, Texas Southern University, Houston, Texas 77004, United States Department of Chemistry, Portland State University, Portland, Oregon 97207, United States Department of Chemistry, Georgia State University, Atlanta, Georgia 30302-4098, United States Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States Department of Chemistry, University of Missouri Columbia, Columbia, Missouri 65211-7600, United States Department of Chemistry, University of Louisville, Louisville, Kentucky 40208, United States Institute of Fluorescence, University of Maryland Baltimore County, Baltimore, Maryland 21202, United States