Haplotyping by capillary electrophoresis

The investigation of the genetic background and phenotype structures of complex diseases, such as cardiovascular or psychiatric disorders and tumors, is one of the most scrutinized fields of the post genomic era. Besides the multiplex analysis of genetic markers and polymorphisms throughout the whole genome, more and more attention is focused on the interaction between the etiological factors of these traits. Haplotype determination, rather than multiplex genotyping seems to be one of the first building blocks of this endeavor. This review focuses on the importance and theoretical background of haplotyping, and summarizes the recent examples of novel and emerging haplotyping techniques by capillary gel electrophoresis based DNA fragment analysis, a powerful tool for the examination of the inheritance of complex traits.     

Preparation of new 2,3-diphenylpropenoic acid esters - good yields even for the more hindered Z isomers

The potassium salt of E- and Z-2,3-diphenylpropenoic acids prepared in situ could be esterified efficiently in DMSO with the appropriate alkyl halides at room temperature. In this way 10 previously undescribed esters of these acids were synthesised and characterised. Excellent yields were observed for most of the E isomers and the more hindered Z esters were also obtained in good yields, far better than those obtained applying the classical acid-catalysed esterification reaction.     

Chemical reactivity of [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts

The chemical reactivity of the [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts towards morpholine, water and sodium methoxide have been studied. Among others, new 1-aza and 2-azabutadienes substituted by a [1,2,3]-triazole ring were obtained in the course of the opening of the positively charged pyrimidine ring.     

Stereocontrolled synthesis of cis-dibenzoquinolizine chlorofumarates: curare-like agents of ultrashort duration

The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]quinolizine methiodide 10 and the analogous quaternizations of 1-benzyl- and 1-phenylisoquinoline congeners 5b and 5c. In this report, we describe stereoselective preparation of the unique cis-dibenzoquinolizinium propanols 15 and 16and their transformation into bis- and mixed-onium chlorofumarates 19, 20ab, and 26. Dibenzo[a,g]quinolizinium propanol 15 was prepared enantioselectively in three steps from dihydroisoquinoline 11. Asymmetric transfer hydrogenation of 11 in the presence of triethylamine/formic acid and Noyori's chiral ruthenium catalyst 12 produced R-(-)-5',8-dimethoxynorlaudanosine (13) in 98% yield and 87% ee. Pictet-Spengler cyclization of 13 in formalin/formic acid afforded the dibenzo[a,g]quinolizine 14 in 65% yield. Quaternization of 14 with 3-chloro-1-propanol under Finkelstein conditions generated cis-dibenzoquinolizinium propanol 15 in 85% yield with >94% cis-selectivity. The cis-dibenzo[a,h]quinolizinium propanol 16 was obtained as a single stereoisomer by reaction of the known tetramethoxyquinolizine 9 with neat 3-iodo-1-propanol. Bis-onium chlorofumarates 18 and 19 and the mixed-onium derivative 20ab were prepared by a pool synthesis procedure from (1R)-trans-6a, 16, and chlorofumaryl chloride (17). Mixed-onium alpha-chlorofumarate 26 was synthesized from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.     

Cyclocondensation reaction of a 1,5-diketone with 1,2-diamines

Reaction of 2-acetonyl-4,5-dimethoxy-3′-chlorobenzophenone (1) with ethylenediamine afforded the imidazo[2,1-a]isoquinoline 2, whereas 6-(3-chlorophenyl)-8,9-dimethoxybenzo[b]phenazine (3) and naphthol 4 were obtained with ortho-phenylenediamine.     

Material transport between the atmosphere and sediment of the Lake Balaton

A monitoring system was developed to gain information on the present level of pollutants in the Lake Balaton, Hungary. Determination of 13 polycyclic aromatic hydrocarbons (PAHs) and inorganic pollutants (mostly toxic metals) in aerosol, precipitation and sediment samples was carried out. The aim of collecting aerosol and precipitate samples in the same site at the same period was to determine the distribution of elements in two depositions. For the fractionation by particle size, aerosols were sampled by a cascade impactor. A simple three-stage sequential leaching procedure was applied to establish the distribution of metals among environmentally mobile, bound to carbonates and oxides, and environmentally immobile, (bound to silicates) fractions in aerosols. Sediment samples were collected from 17 different sites inside of the lake and 10 sites at harbors at 30–70 cm in depth. Core samples were cut to 10-cm pieces, dried at room temperature, and finally passed through a 63-μm sieve. Total concentrations of elements were determined by atomic absorption spectrometry (AAS) after an acidic digestion. The concentrations of PAHs were determined by HPLC method with fluorescence detection.In aerosol samples collected from September 6, 2002 to January 26, 2003, concentration of Cd was <0.1 μg/m³, and the majority of Cd has been found in the mobile fraction. Cadmium was associated to particles between 0.25 and 2 μm indicating the anthropogenic origin. Similar distribution of Pb was obtained in all seasons, and the highest concentration of Pb was found as 8.6 ng/m³ in particle size of 0.7 and 1.4 μm. Results of total concentration of elements of bottom sediments of the Lake Balaton and harbors were compared to Interim Sediment Quality Guideline (ISQG) values and the Probable Effect Level (PEL) values. Data showed that the average concentrations of elements were usually less than those of ISQGs and other background data for soils and geochemical values. The sediment is not polluted and its disposal is feasible. There is no direct correlation between the concentration of elements deposited onto the surface of the lake from dry and wet deposition and the upper part of the sediment. So, from the budget of the deposition, the concentration of elements in the upper layer of the sediment cannot be predicted.Seasonal changes of the concentration of PAHs in aerosol was observed, samples collected at winter contained the highest values. In December–January 2002/2003, the wet deposition was found as 64 μg/m² period. Among the individual compounds, the wet deposition rate of phenantrane, fluoranthene and pyrene was dominant, while for dry deposition, these compounds were fluoranthene and pyrene. The concentrations of ∑PAHs found for all sites and depth of sediment samples ranged from 11 to 1734 μg/kg dry weight with an average of 132 μg/kg. These values represent a quite low pollution level compared to other sediment with anthropogenic influence. Based on the results, it can be definitely confirmed that the chemical quality of the water and sediment of the Lake Balaton is satisfactory.     

Effect of pressure on retention factors in HPLC using a non-porous stationary phase

Summary Pressure and temperature have significant influence on retention in HPLC. This study investigates the effect of pressure and temperature on the retention behavior of aromatic hydrocarbons (toluene, ethyl benzene, butyl benzene, pentyl benzene) and polar, acidic and basic samples (phenol, acetophenone, N,N-dimethyl aniline, benzophenone) on a reversed phase column. The effect has been studied on non-porous, tetradecyl (C₁₄) coated silica particles. We found that the adsorption-induced decrease of the partial molar volume of the solutes investigated was between ΔV _m =5–15 cm³ mol⁻¹. The increment of the decrease of the partial molar volume due to the addition of one CH₂ group, for the homologous series of the aromatic hydrocarbons is approximately ΔV _CH2 =2.3 cm³mol⁻¹. Presented at Balaton Symposium '01 on High-Performance Separation Methods, Siófok, Hungary, September 2–4, 2001.     

Comparison of the fragility index of different eudragit polymers determined by activation enthalpies

The present study aimed to apply fragility index (m) of polymers in the determination of the optimal amount of plasticizer in polymer films. The fragility index of different Eudragit polymers (RS, RL, EPO) was assessed by differential scanning calorimerty (DSC), applying the Arrhenius connection (logq–1/T _g). The fragility of Eudragit EPO films proved to be the highest, while in the case of RS and RL, the increase of the alkyl-chain length caused the increase of fragility. Studying the effect of plasticizer (triethyl citrate, TEC) on the m value of Eudragit RL and RS films, a near linear reduction of the fragility index could be observed between 5–30% TEC concentration, but above 30%, this value leveled out to constant.     

Ruthenium Carbonyl Cluster Complexes with Phenylgermyl Ligands from the Reactions of Ph<Subscript>3</Subscript>GeH with Ru(CO)<Subscript>5</Subscript> and Ru<Subscript>3</Subscript>(CO)<Subscript>12</Subscript>

Four new triphenylgermylruthenium carbonyl compounds HRu(CO)₄GePh₃, 14; Ru(CO)₄(GePh₃)₂, 15; Ru₂(CO)₈(GePh₃)₂, 16; and Ru₃(CO)₉(GePh₃)₃(μ-H)₃, 17 were obtained from the reaction of Ru(CO)₅ with Ph₃GeH in hexane solvent at reflux, 68 °C. The major product 14 was formed by loss of CO from the Ru(CO)₅ and an oxidative addition of the GeH bond of the Ph₃GeH to the metal atom. This six coordinate complex contains one terminal hydrido ligand. Compound 15 is formed from 14 and contains two trans-positioned GePh₃ ligands in the six coordinate complex. Compound 16 contains two Ru(CO)₄(GePh₃) fragments joined by an Ru–Ru single bond. Compound 17 contains a triangular cluster of three ruthenium atoms with three bridging hydrido ligands and one terminal GePh₃ ligand on each metal atom. When heated to 125 °C, 14 was converted to the new triruthenium compound Ru₃(CO)₁₀(μ-GePh₂)₂, 18. Compound 18 consists of a triangular tri-ruthenium cluster with two GePh₂ ligands bridging two different edges of the cluster and one bridging CO ligand. Ru₃(CO)₁₂ was found to react with Ph₃GeH at 97 °C to yield three products: 15, and two new compounds Ru₃(CO)₉(μ-GePh₂)₃, 19 and Ru₂(CO)₆(μ-GePh₂)₂(GePh₃)₂, 20 were obtained. Compound 19 is similar to 18 having a triangular tri-ruthenium cluster but has three bridging GePh₂ ligands, one on each Ru–Ru bond. Compound 20 contains only two ruthenium atoms joined by a single Ru–Ru bond that has two bridging GePh₂ ligands and a terminal GePh₃ ligand on each metal atom. All compounds were characterized by a combination of IR, ¹H NMR, single-crystal X-ray diffraction analyses. This report is dedicated to Professor Dieter Fenske on the occasion of his 65th birthday for his many pioneering contributions to the chemistry of metal chalcogenide cluster complexes.