Outer-Sphere Ligand Exchange Chromatography on Bonded Chiral Silica Gel

Abstract

A bonded chiral phase for HPLC, obtained by reaction between a porous silica gel modified with N(aminoethylamino)propyl groups, and A(+)[Co(en)₂(NO₂)] Br, was prepared in order to sepa rate optical isomers by a outer-sphere complex mechanism. The extent of the stereoselectivity of this support was tested by sampling racemates of organics acids and of tris-oxalate complexes of cobalt(III) and chromium(III). Good resolution was achieved when strong interactions of the solute (tri-oxalates complexes) with the support were involved.     

THE PHENOMENON OF KRYPTORACEMIC CRYSTALLIZATION. PART 1. COUNTERION CONTROL OF CRYSTALLIZATION PATHWAY SELECTION. PART 4. THE CRYSTALLIZATION BEHAVIOR OF (+/−)-[Co(tren)(NO2)2]Br(I), (+/−)-[Co(tren)(NO2)2]2Br(ClO4) · H2O(II), (+/(−)-[Co(tren)(NO2)2]ClO4(III) AND ATTEMPTS TO SOLVE THE STRUCTURE OF (+/−)-[Co(tren)(NO2)2]NO3(IV)

Abstract

Racemic aqueous solutions of (+/?)-[Co(tren)(NO₂)₂]Br (I), (+/?)-[Co(tren)(NO₂)₂]ClO₄ (III) and [Co(tren)(NO₂)₂]NO₃(IV) crystallize as racemates. By contrast, the double salt, (+/?)-[Co(tren)(NO₂)₂]₂Br(ClO₄) · H₂O(II), produces kryptoracemic crystals belonging to the enantiomorphic space group P2₁2₁2₁ (No. 19). The former three species crystallize with one molecule in the asymmetric unit; in the latter, a racemic pair is the asymmetric unit, a fact which is hidden by the enantiomorphic nature of its space group – thus the name of the crystallization phenomenon reported. In (II) pairs of cations are related by an approximate, non-crystallographic, inversion center. The crystal structure and polarity of (I) and the absolute configuration of (II) were determined by refinement. The crystalline contents of (I) to (III) consist of infinite strings of hydrogen bonded cations, the counter ions and (where relevant) waters of crystallization acting as a hydrogen-bonding glue linking the spiral strings

In (II), the N-CH₂-CH₂-NH₂-Co rings of Co(1) are (δδλ) and those of Co(2) are (λλδ) and adjacent strings are linked by the counter-anions and the water of crystallization. Pairs of Co(1) and of Co(2) cations are hydrogen bonded to one another by two N-O···H-N linkages. Finally, pairs of composition Co(1)-Co(1) as well as of Co(2)-Co(2) share another pseudo-inversion center which is approximately valid for the CoN₆ portion of each cation. Since the atoms of the cation are ordered, it is impossible for the pseudo-inversion center to be valid for the -CH₂-CH₂- fragment of the Co(1)-Co(1) or of Co(2)-Co(2) pairs. (I) and (III) crystallizes as racemates whose five-membered rings have chiroptical symbols (δδλ), or its enantiomer.     

Investigation of Enantiomer Separation by LC with a New Bonded Cellulose 3,5-Dimethylphenylcarbamate Chiral Stationary Phase

A chiral stationary phase has been prepared from the 3,5-dimethylphenylcarbamate of cellulose chemically bonded to 3-aminopropylsilica gel at the 6-positions of the glucose units. The phase has been used to study direct liquid chromatographic enantioselective separation of five racemates. The effects on resolution of modifiers (alcohols, THF, and chloroform), flow rate, and temperature were investigated. It was found that the concentration and structure of the alcohol modifier can affect the separation; enantiomer separations were improved to different extents by addition of THF or chloroform to the mobile phase. Flow rate and temperature can also effect the resolution of racemates. In the range 10–40°C there was a linear relationship between ln k (or ln α) and 1/T (r > 0.98) for four of the compounds. These results indicate retention mechanism does not change as a function of temperature.     

Applications of Cellulose-Based Chiral Stationary Phases in the Resolution of Some Beta-Adrenoceptor Antagonists

Abstract

Cellulose tris (3,5-dimethylphenyl carbamate) known as Chiralcel OD chiral stationary phase (CSP) is one of the most commonly used cellulosic CSPs which have been successfully used for separation, enantiomeric purity determination and analysis of several drug racemates including β-adrenoceptor antagonists.

Resolution of timolol, penbutolol, celiprolol and carazolol enantiomers are achieved using this CSP. A possible chiral recognition mechanism(s) for these β-adrenergic blockers and this chiral stationary phase is presented.     

HPLC separation of the enantiomers of racemic benzergoline derivatives on a chiral binaphthalene covalently bonded to silica gel

A novel chiral stationary phase (CSP) derived from the atropisomeric enantiomer S-3,3′-dicarboxy-2,2′-dihydroxy-1,1′-binaphthyl (S-DDBN) has been synthesized and its use for the separation of enantiomers demonstrated. The chiral selector is covalently bonded to amino-functionalized silica gel, thus enabling the use of alcohols as mobile phases. Good chiral discrimination was obtained for the pharmacologically interesting class of benzergoline derivatives which act as selective dopamine D₁ receptor agonists. This paper reports the successful separtion of fifteen structurally related benzergoline racemates with separation factors up to 3.5. The influence of small differences in molecular structure on chiral discrimination was examined.     

Reverse-Phase HPLC of Proteins: Effects of Various Bonded Phases

Abstract

A variety of organic phases bonded to silica can be used effectively for the reverse-phase high performance liquid chromatography of large proteins. These include octyl, octadecyl, cyanopropyl and diphenyl bonded phases. The differences in retention characteristics and selectivity among these bonded phases is demonstrated with several standard proteins.     

Liquid Chromatographic Resolution of Enantiomers on Chiral Amide Bonded-Silica Gel Normal Phase Separation of Racemic α-Amino Acid Derivatives by N-Acetyl-L-valyl-aminopropyl-silanized Silica (AVA) Phase

Abstract

A new optically active stationary phase obtained by grafting N-acetyl-L-valine with 3-aminopropylsilanized silica was developed. The high-efficiency chiral column was prepared by slurry packing procedure. Direct resolution of the racemates of α-amino acid derivatives was accomplished by using normal phase liquid chromatography.     

Preparation and chromatographic evaluation of a chiral stationary phase based on carboxymethyl-β-cyclodextrin for high-performance liquid chromatography

A novel chiral stationary phase (CSP) was prepared by chemically bonding carboxymethyl-β-cyclodextrin (CM-β-CD) onto 3-aminopropyl silica gel and showed excellent enantioseparation abilities for a broad range of chiral compounds and drugs.     

Synthesis of the Racemates of the b-Carboline Alkaloid Chrysotricine and its Diastereomer

Summary.  The racemates of the rubiacea alkaloid Chrysotricine (1) and its diastereomer are synthesized from the isomeric mixture of linalyl oxides 3 and tryptamine in six steps, followed by separation of the diastereomers. Received November 11, 1999. Accepted November 25, 1999     

L-N-(3,5-Dimethoxybenzoyl)isoleucine chiral stationary phase for separation of enantiomers by HPLC

Summary L-N-(3,5-dimethoxyoxybenzoyl)isoleucine, ionically bonded to γ-aminopropyl silica, has been tested as a chiral stationary phase for the separation of racemates by HPLC. The phase shows good selectivity towards different types of racemates and in particular for those having an electron-poor aromatic group in their molecule. The separation of benzoin racemate can be achieved on the developed chiral phase with an α value of 1.10.     

Preparation of Various Bonded Phases for HPLC Using Monochlorosilanes

Abstract

Monochlorosilanes have been prepared with yields of about 80% through a catalytic hydrosilylation of terminal olefins. Subsequently, the silanes are chemically bonded to silica to obtain: (i) n-octyldimethylsilyl bonded phases with reproducible surface coverage ranging from 0.8 to 3.5 μmol/m², (ii) propyldimethylsilyl bonded phases with different functional groups at the γ-position, all showing a nearly equal surface coverage of some 3.3 μmol/m², and (iii) n-alkyldimethylsilyl bonded phases with chainlengths ranging from 1 to 22 carbon atoms and with surface coverages ranging from 3.9 μmol/m² for RP-1 to 3.0 μmol/m² for the RP-22 bonded phase. A simplified model based on the pore structure of silica allows an explanation and estimation of the maximum surface coverage as a function of the chainlength of the bonded phase.     

Synthesis,structure, and electrochemistry of mer[RuCl3(DMSO–S)(DMSO–O)(py)]

Reaction of mer-[RuCl₃(DMSO–S)₂(DMSO–O] (1) with pyridine (py) in dichloromethane yields mer-[RuCl₃(DMSO–S)(DMSO–O)(py)] (2). A single crystal suitable for X-ray diffraction was obtained by recrystalization with dichloromethane and diethyl ether. X-ray diffraction analysis revealed an unusual case in which two independent molecules (2a and 2b) are present in the asymmetric unit cell. Both molecules have distorted octahedral geometry in which DMSO is bound through oxygen and sulfur. Density functional theory (DFT) calculations were performed for 2a and 2b in gas phase to investigate bonding shown by the two DMSO ligands. Optimizations were done on both DMSO ligands bonded through S, both DMSO ligands bonded through O, one DMSO bonded through O, and the other through S but opposite to the actual molecule. The energy differences of the optimized structures were calculated.     

Synthesis of Chemically Bonded Polystyrene-Divinylbenzene on Silica by Free Radical Initiation with Gamma Radiation Cross-Linking

Abstract

A procedure is described for direct chemical bonding of polystyrene-divinylbenzene (PS-DVB) to silica. The method is a two-step process which first bonds and polymerizes the material via peroxide initiation in the presence of azobisisobutyronitrile (AIBN). The second step involves cross-linking the bonded polymer by gamma irradiation. The success of the procedure is evaluated by carbon-hydrogen analysis and DRIFT spectroscopy of the product. Chromatographically the bonded material is tested by separations of alkylarylketones.     

The induced circular dichroism of helically shaped racemic bilatrienes

Summary The imperfect mirror image relationship of the circular dichroism of (M) and (P) helical biliverdins bound to a homochiral entity (ICD) has been studied using the kinetically stable racemates (M+P)2 and (M+P)3. The phenomena associated with and eventual implications for the interpretation of ICD spectra of naturally occurring kinetically labile biliverdins in terms of chiral recognition are discussed.Dedicated to ProfessorKarl Schlögl on the occasion of his 70^th birthday     

Enantiomeric Resolution of Amino Acids by Reversed Phase High Performance Liquid Chromatography Using a New Chiral Mobile Phase

Abstract

The synthesis of a new chiral agent, (R,R) (-)N, N'-trans-1, 2-dihexylcyclohexanediamine, for the chromatographic resolution of racemates is reported. Highly selective separations of D- and L-isomers of free and Dns-amino acids were accomplished on a reversed-phase column using in the mobile phase a Cu(II) complex of the above chiral selector. The procedure was extended to resolve diastereomeric derivatives, which were obtained by reaction of an optically active amine with o-phthaldeyde in the presence of N-acetyl-L-cysteine.     

Comparison of Reagents for Lipid and Phospholipid Detection and Densitometric Quantitation on Silica Gel and C18 Reversed Phase Thin Layers

Abstract

A variety of chromogenic and fluorogenic detection reagents were evaluated for detection and densitometric quantification of lipids and phospholipids on silica gel and chemically bonded octadecylsilane reversed phase thin layer plates. Phosphosphomolybdic acid (PMA) was found to be the most generally favorable reagent, followed by cupric acetate and ethanolic sulfuric acid. The quantification of lipids in blood serum by chemically bonded RP-TLC was demonstrated using PMA with direct sample application to preadsorbent plates.     

Stereoselective Synthesis and Resolution of P-Chiral Phosphine Chalcogenides.

Abstract

New synthetic methods and resolution procedures securing ready access to the resolved P-chiral phosphinoylethenes, phosphinoylacetates and secondary phosphine oxides of diversified structures have been developed. The methods are based on processes employing stereoselective nucleophilic displacement at phosphorus, asymmetric deprotonation, immolative vinyl and chirality transfer from sulfur to phosphorus, chemical and enzymatic kinetic resolution, resolution via covalent diastereoisomers, as well as direct resolution of racemates by classical resolving agents and by chromatography on chiral stationary phases.     

Influence of Bonded-Phase Column Type,Mobile Phase Composition,Temperature and Flow-Rate in the Analysis of Triglycerides by Reverse-Phase High Performance Liquid Chromatography

Abstract

Two chromatographic systems for RP-HPLC analysis of triglycerides, operating under isocratic conditions using octadecylsilane and octylisilane bonded phases, are described.

The influence of such chromatographic factors as bonded phase column type, mobile phase composition, temperature and flow rate on retention, analysis selectivity and efficiency, and separation of mixtures of homogeneous triglycerides was assessed. Linear relationships were established for the logarithm of the capacity factor and selectivity for each triglyceride in relation to temperature, the proportion of certain mobile phase components and flow rate.

The octadecylsilane bonded phase was more selective when analyzing triglycerides with a partition number below 48, while octylsilane was appropiate for separating mixtures of long chain saturated triglycerides to the detriment of the resolution of triglycerides with low partition numbers. ACN/ACE/THF (58/38/4) was a suitable mobile phase for use with the octadecylsilane bonded phase, and ACN/THF /H₂O (60/40/1) for the octylsilane bonded phase. A column temperature of 30°C and a flow rate of 1.5 mL/min resulted in acceptable resolution and analysis time in both systems.     

The Determination of Sodium Monofluoroacetate (Compound 1080) in Formulation and Technical Samples by High Pressure Liquid Chromatography

Abstract

A high pressure liquid chromatographic (HPLC) procedure was developed for the determination of sodium monofluoroacetate (Compound 1080). The procedure utilized an amine (NH₂) bonded column for the reverse phase determination of sodium monofluoroacetate in formulation and technical samples.     

Chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin immobilized on porous silica for enantioseparation

In this work, a series of chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin bonded stationary phase for high performance liquid chromatography (HPLC) were synthesized via a simple one-pot synthesis approach. Various racemates (aryl alcohols, flavanones, triazoles, benzoin, etc.) were well separated on the tricarboxylic acid modified chiral stationary phases in both normal and reversed modes with good reproducibility and stability, and the influence of mobile phase composition on resolution (R_s) were deeply investigated. The RSD values of R_s for repeatability and column-to-column were below 1.28% and 3.05%, respectively. Hence, the fabrication of tricarboxylic acid modified chiral stationary phase (CSPs) is a new efficient strategy to improve the application of β-cyclodextrin as CSPs in the field of chromatography.