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Biomedical subjects

I M Warner

Publications and source records attributed to I M Warner.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterization and thermodynamic studies of the interactions of two chiral polymeric surfactants with model substances: phenylthiohydantoin amino acids.

Analytical ultracentrifugation is used for determination of the molecular weights and the sedimentation coefficients of poly(sodium undecanoyl-L-valinate) (PSUV) and poly(sodium undecanoyl-L-threoninate) (PSUT) at different temperatures. Plots of absorbance as a function of radius indicates that both PSUV and PSUT are highly monodispersed. A method for evaluating the partial specific volumes using density measurements is presented. The partial specific volumes of PSUV are slightly higher than those of PSUT. In addition, the temperature dependence of the retention factor in electrokinetic chromatography was used to estimate the enthalpy, the entropy, and the Gibbs free energy of the surfactant/analyte complexes. Five phenylthiohydantoin-DL-amino acids were separated and each enantiomeric pair was completely resolved. Comparison of the thermodynamic values obtained with PSUV vs PSUT using a van't Hoff relationship suggests that PSUT, with a less favorable free energy change (i.e., less negative delta (delta G)), generates a more positive entropy change, hence slightly less chiral resolution.

Biopolymers↗
PubMed1999

Evaluating chiral separation interactions by use of diastereomeric polymeric dipeptide surfactants.

Poly sodium N-undecyl leucine-leucine (poly SULL) is used as a diagnostic tool to investigate chiral molecular interactions via electrokinetic chromatography (EKC). Poly SULL has two chiral centers which are defined by two asymmetric carbons. Each chiral center of poly SULL can have two possible configurations (D or L). Consequently, four different optical configurations are possible within the surfactant molecule (L-L, D-D, L-D, and D-L). In this study, five chiral analytes of various charge states and hydrophobicities were used to investigate the role of electrostatic interactions and hydrophobicity on chiral recognition with polymeric dipeptide surfactants. These studies lead to a proposed hypothesis for interaction of the analytes with dipeptide surfactants. The hypothesis was tested and the contribution of the double chiral centers to this interaction was evaluated by use of two dipeptide surfactants in which one chiral amino acid is replaced by an achiral amino acid glycine, i.e., poly sodium N-undecyl L-leucine-glycine (poly L-SULG) and poly sodium N-undecyl L-glycine-leucine (poly L-SUGL). The results reported here provide new insights into the mechanism for chiral recognition of select chiral analytes by use of polymeric chiral surfactants.

Adrenergic beta-Antagonists↗
PubMed1999

Amino acid order in polymeric dipeptide surfactants: effect on physical properties and enantioselectivity.

The effect of amino acid order on chiral selectivity in polymeric dipeptide surfactants, as well as the physical properties of the surfactants, is investigated. An understanding of enantioselectivity of such dipeptide surfactants is crucial to the design of more efficient polymeric surfactants and has implications in other areas of research such as enantioselective interactions of amino acid based compounds (i.e., enzymes, hemoglobin, antibodies, etc.). It should be noted that such polymeric surfactants are not easily crystallized. Therefore, in a manner similar to the study of proteins, fluorescence spectroscopy is a powerful tool used to study the structure-function relationship of these polymeric surfactants. The microenvironments inside the core of 18 polymeric surfactants were characterized using the environmentally sensitive probes pyrene and 6-propionyl-2-(dimethylamino)naphthalene (Prodan). The surfactants examined in this study include all possible dipeptide combinations of the L-form of alanine, valine, and leucine and the achiral amino acid glycine (except glycine-glycine) as well as the single amino acid surfactants of alanine, valine, and leucine. The results of the fluorescent probe studies led to a proposed structure of the polymeric dipeptide surfactants in solution. The implications of the proposed structure for chiral selectivity were tested with two model atropisomers, (+/-)1,1'-bi-2-naphthol and (+/-)1,1'-bi-2-naphthyl-2,2'-diyl hydrogen phosphate, using capillary electrokinetic chromatography.

Amino Acid Sequence↗
PubMed1999

Electrokinetic chromatography of twelve monomethylbenz[a]anthracene isomers using a polymerized anionic surfactant.

A method for the separation of twelve monomethyl-substituted benz[a]anthracene isomers using poly-(sodium undecylenic sulfate) (poly-SUS) surfactant by means of electrokinetic capillary chromatography (EKC) is described. Several parameters such as concentration of acetonitrile (ACN), pH, as well as applied voltage were studied to optimize the EKC separation. ACN at a concentration of 35% v/v, 12.5 mM phosphate-borate buffer, 30 kV with 0.5% w/v poly-SUS at a pH of 9.5 provided a resolution of a mixture of nine out of twelve methylbenz[a]anthracene (MBA) isomers in 50 min. The results of this study suggest that molecular length of MBA rather than length-to-breath ratio plays an important role in the elution order of some isomers.

Acetonitriles↗
PubMed1999

Chiral electrokinetic chromatography using dipeptide polymeric surfactants: present state of the art.

Polymeric amino acid based surfactants have been recently employed as pseudostationary phases in capillary electrophoresis. These phases are effective for chiral separation of analytes in different charge states and hydrophobicities. This review paper focuses on polymeric dipeptide surfactants. The benefits of dipeptide over single amino acid micelle polymers are shown. Some aspects of dipeptide surfactants that are presented here includes the amino acid order, effect of number and position of chiral centers, and steric factors on enantiomeric separation of chiral compounds in different charge states. In addition, the preferential site of interaction of the chiral analyte using diastereomers of polymeric dipeptide surfactants is discussed.

Amino Acids↗
PubMed1999

NMR and molecular mechanics study of pyrethrins I and II.

Bioassay-directed fractionation of the organic extract of the Kenyan pyrethrum flowers (Chrysanthemum cinerariaefolium Vissiani) resulted in the isolation of two natural pyrethrin esters, pyrethrin I (PI) and pyrethrin II (PII) as the major constituents. These esters elicited inhibition of the multiple drug resistant (MDR) Mycobacterium tuberculosis. The high-field (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of PI and PII were unequivocally assigned using modern two-dimensional (2D) proton-detected heteronuclear multiple-quantum coherence (HMQC) and heteronuclear multiple-bond correlation (HMBC) experiments. The conformations of both esters were deduced from (1)H-(1)H vicinal coupling constants and confirmed by 2D nuclear Overhauser effect spectroscopy (NOESY). Computer molecular modeling (MM) studies revealed that PI and PII molecules adopt a "love-seat" conformation in chloroform (CDCl(3)) solution.

Chrysanthemum cinerariifolium↗
PubMed1998

Cationic beta-cyclodextrin derivative for chiral separations.

A novel hepta-substituted beta-cyclodextrin bearing the methoxyethylamine group linked to the upper cyclodextrin rim was successfully used as a chiral selector for enantiomeric separation of non-steroidal anti-inflammatory drugs (NSAIDs) and phenoxypropionic acid herbicides (PPAHs). Separation parameters such as pH and concentration were found to have major influences on enantiomeric resolution of the NSAIDs and PPAHs. Results indicate that heptakis(6-methoxyethylamine-6-deoxy)-beta-cyclodextrin [beta-CD-OMe (VII)] performs exceptionally well for the enantiomeric resolution of NSAIDs: indoprofen and fenoprofen (Rs = 11 and 14, respectively). In addition, baseline enantiomeric separation of a mixture of six pairs of PPAHs was achieved in under 30 min. Compared to other cationic beta-cyclodextrins reported in the literature, the beta-CD-OMe (VII) showed improved selectivity for both classes of the aforementioned anionic racemates.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Capillary zone electrophoresis of bile acids with indirect photometric detection.

Investigations in our laboratory have demonstrated that capillary zone electrophoresis (CZE) with indirect photometric detection is a viable approach to the separation and identification of free bile acids along with their taurine and glycine derivatives. Various parameters such as pH, organic solvent concentrations, column temperature, and type of chromophore electrolyte were investigated to optimize the electrophoretic separation and to maximize the peak capacity. The quality of separation of bile acids can be dramatically improved by incorporating gamma-cyclodextrin (gamma-CD) in the running electrolyte. This improvement in resolution is accompanied by a decreased migration time, suggestive of an increase in association of gamma-CD with bile acids. As a result, a CZE separation of all 15 bile acids was possible in approximately 30 min using 5 mM adenosine 5'-monophosphate, 7 mM gamma-CD in 75% (v/v) methanol at pH 7.0.

Adenosine Monophosphate↗
PubMed1998

Chiral separations using dipeptide polymerized surfactants: effect of amino acid order.

Chiral separations using various polymerized dipeptide surfactants in electrokinetic capillary chromatography (EKC) are investigated. The two main dipeptide surfactants used in this study were sodium N-undecylenyl-L-valine-L-leucine (L-SUVL), and sodium N-undecylenyl-L-leucine-L-valine (L-SULV). These studies were performed in order to determine if the order of amino acids in dipeptide surfactants is important in terms of chiral recognition and separations. Both the monomer and the polymer of these two surfactants were compared for the separation of two model atropisomers, (+/-)-1,1-bi-2-naphtol (BOH) and (+/-)-1,1'-bi-2-naphthyl-2,2'-diyl hydrogen phosphate (BNP). Some advantages and disadvantages of the polymer relative to the monomer are discussed. Four other surfactants, the polymers of sodium N-undecylenyl-L-leucine-L-leucine (L-SULL), sodium N-undecylenyl-L-valine-L-valine (L-SUVV), sodium N-undecylenyl-L-valine (L-SUV), and sodium N-undecylenyl-L-leucine (L-SUL), were also used in this study, and their performance was compared to that of poly(L-SULV). These data show conclusively that the order of amino acids in dipeptide surfactants has a dramatic effect on chiral recognition. Our investigations indicate that poly-(L-SULV) provides the best enantioselectivity among the four dipeptide and two single amino acid surfactants for the separation of BNP and BOH. The advantages of poly-(L-SULV) are demonstrated via the ultrafast separation of the enantiomers of BNP and BOH in less than 1 min.

Amino Acids↗
PubMed1998

Enhanced separation of antidepressant drugs using a polymerized nonionic surfactant as a transient capillary coating.

The separation of seven structurally similar antidepressant drugs (amitriptyline, nortriptyline, imipramine, desipramine, protriptyline, doxepin, and nordoxepin) was achieved in under 15 min using a novel nonionic micelle polymer, poly(n-undecyl-alpha-D-glucopyranoside) (PUG) by use of capillary zone electrophoresis (CZE). Systematic studies with varying polymer concentration, pH, and percent organic modifier were conducted in order to find the optimum conditions for baseline separation of the seven tricyclic antidepressants. In addition, equations for capacity factor were used to estimate the extent of what was initially thought to be micelle analyte interaction. A series of calculations show that a modified CZE system (PUG-CZE) was the actual mode of separation. Thus, our study concluded that PUG functioned in a non-electrokinetic chromatography mode.

Antidepressive Agents↗
PubMed1998

On-line capillary electrophoresis-electrospray ionization mass spectrometry using a polymerized anionic surfactant.

On-line capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has been used to determine the tricyclic antidepressant drugs (imipramine, doxepin, and amitriptyline) as well as the beta-adrenergic blocker drugs (propranolol and alprenolol). A CE-ESI-MS interface linking a manually operated CE system and a Finnigan MAT-900 sector mass spectrometer (with an Analytica electrospray ionization source) has been constructed in-house and employed for this study. Although a water/methanol based capillary zone electrophoresis (CZE) buffer was initially used to determine these analytes, enhanced resolution was obtained by addition of a polymerized surfactant, i.e., poly-sodium undecylenic sulfate (poly-SUS), into the electrokinetic chromatography (EKC) buffer. When a low concentration of this poly-SUS surfactant was added to a volatile EKC buffer, these structurally similar cationic drugs were EKC separated and on-line detected by ESI-MS.

Adrenergic beta-Antagonists↗
PubMed1997

A persubstituted cationic beta-cyclodextrin for chiral separations.

The applications of a novel polycationic derivative of beta-cyclodextrin (beta-CD), heptakis(6-hydroxyethylamino-6-deoxy-beta-cyclodextrin) (beta-CD-EA), as a chiral host--guest additive for the enantioseparation of various classes of chiral anionic analytes are presented. The cationic beta-CD described in this paper is persubstituted with seven ethanolamine side arms at the primary rim of each cyclodextrin (CD) molecule. It is found that the electrophoretic mobility of beta-CD-EA can be adjusted to influence the chiral selectivity by changing the pH of the background electrolyte. Most of the observed CD capillary zone electrophoresis (CZE) separations of anionic drugs and herbicides were accomplished in the pH range of 4.0-7.0 with a reverse polarity configuration. At pH 5.0, enantioseparation of a mixture of three structurally related antiinflammatory agents (fenoprofen, flurbiprofen, and ibuprofen) was possible in about 30 min. However, other chiral acids, such as a series of phenoxypropionic acid herbicides and dansylated amino acids (glutamic acid and aspartic acids), were best separated at pH 6.0 or 7.0. An impressive separation of a mixture of six structurally related anionic herbicides [(+/-)-2-phenoxypropionic acid, (+/-)-2-(2-chlorophenoxy)propionic acid, (+/-)-2-(3-chlorophenoxy)propionic acid, (+/-)-2-(4-chlorophenoxy)propionic acid, (+/-)-2-(2,4-dichlorophenoxy)propionic acid, and (+/-)-2-(2,4,5-trichlorophenoxy)propionic acid] was achieved for the first time in about 15 min during a single run with 20 mM beta-CD-EA. The analytical applicability of this cationic CD molecule for chiral separations is discussed in detail.

Amino Acids↗
PubMed1997

Improved chiral separations using a polymerized dipeptide anionic chiral surfactant in electrokinetic chromatography: separations of basic, acidic, and neutral racemates.

Two polymeric chiral anionic surfactants [poly(sodium N-undecylenyl-L-valine) (poly-L-SUV) and poly(sodium N-undecylenyl-L-valine-valine) (poly-L-SUVV)] are compared as pseudostationary phases for chiral separations of basic, acidic, and neutral enantiomers. Parameters such as pH, concentration and type of background electrolyte, concentration of polymerized chiral surfactants, and injection size were studied to investigate the migration behavior and optimize the chiral resolution of several racemic analytes. At equivalent monomer concentrations, the migration factors for cationic enantiomers were larger with poly-L-SUV than with poly-L-SUVV. In contrast, the reverse was true for anionic enantiomers. However, in both cases, chiral recognition was significantly enhanced with poly-L-SUVV as compared to that with poly-L-SUV. It is interesting to note that the separation selectivity and resolution of a neutral racemate were slightly better with the latter, but only at the expense of longer analysis time and lower efficiencies.

Buffers↗
PubMed1997

Improved chiral separation using achiral modifiers in cyclodextrin modified capillary zone electrophoresis.

The influence of achiral modifiers on the chiral separation of propranolol is examined by cyclodextrin modified capillary zone electrophoresis. The improved chiral separation of propranolol is by molecules previously identified in our group as forming ternary complexes with cyclodextrin and pyrene. The polarity, chain size and heteroatom composition of the functional groups on the comodifiers was systematically varied in order to study the influence of these variables on the separation of propranolol. The improved chiral separation is accompanied by a decrease in retention time. The decrease in retention time is suggestive of a decrease in the association of beta-cyclodextrin (beta-CD) with propranolol which was verified by calculation of apparent association constants using fluorometric methods.

Cyclodextrins↗
PubMed1997

Studies of polymerized sodium N-undecylenyl-L-valinate in chiral micellar electrokinetic capillary chromatography of neutral, acidic, and basic compounds.

The polymerized surfactant poly(sodium N-undecylenyl amino L-valinate) [poly(L-SUV)] has been used in micellar electrokinetic capillary chromatography for the chiral separation of various acidic and basic drugs, as well as neutral compounds. Under the conditions studied, poly(L-SUV) was shown to be a very versatile anionic chiral selector in the pH range of 5.6-11. The micelle was used for the enantioseparation of coumarinic anticoagulant drugs with various buffers under moderately acidic conditions. Neutral and alkaline buffer conditions were used to successfully separate the neutral atropisomers (+/-)-1,1'-bi-2-naphthol, (+/-)-1,1'-binaphthyl-2,2'-diamine, and Tröger's base. Chiral separation of the cationic paveroline drugs, laudanosine, norlaudanosoline, and laudanosoline, was influenced by pH and the use of coated capillaries. The acquired data focused on optimizing the migration times, capacity and separation factors, and electrophoretic mobilities of the various racemic mixtures.

Chromatography↗
PubMed1997

Phosphated surfactants as pseudostationary phase for micellar electrokinetic chromatography: separation of polycyclic aromatic hydrocarbons.

A double alkyl chain di(2-ethylhexyl)phosphate (DEHP) is introduced as a potential anionic micellar pseudophase for a wide range of benzene derivatives and/or polycyclic aromatic hydrocarbons (PAHs). Several parameters such as concentration of phosphated surfactant, type and concentration of organic solvents (acetonitrile, isopropanol, and methanol), as well as capillary electrophoresis separation voltage were optimized to enhance resolution, efficiency and selectivity as well as to maximize peak capacities. The migration times and selectivity order for a number of PAHs differ significantly, depending on the type of organic solvent added to the DEHP surfactant. Acetonitrile at a concentration of 30% v/v in combination with 100 mM DEHP gave optimum separation for a mixture of 21 benzene derivatives and PAHs in under 16 min.

Benzene Derivatives↗