bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR studies of chiral recognition by cyclodextrins
Authors: Dodziuk Helena , Koźmiński Wiktor , Ejchart Andrzej
Published: January 2004

Chiral recognition by cyclodextrins is of considerable importance, especially for pharmaceutical industry, in view of the possible side effects of the second enantiometer of chiral drugs. In general, it manifests itself in all NMR parameters (chemical shifts, coupling constants, NOE and ROE effects, and relaxation rates) on one hand. On the other hand, it allows one to determine the thermodynamic parameters characterizing diastereomeric complexes formed by cyclodextrins with enantiomeric guests. After an introduction and a general discussion of NMR manifestations of chiral recognition by cyclodextrin, the existing literature data on this problem will be discussed herein. Chirality 16:90–105, 2004. © 2004 Wiley‐Liss, Inc
Stereospecific synthesis of “para‐hydroxymexiletine” and sodium channel blocking activity evaluation
Authors: Catalano Alessia , Carocci Alessia , Fracchiolla Giuseppe , Franchini Carlo , Lentini Giovanni , Tortorella Vincenzo , De Luca Annamaria , De Bellis Michela , Desaphy Jean‐Francois , Conte Camerino Diana
Published: January 2004

Both enantiomers of “para‐hydroxymexiletine” (PHM), one of the main metabolites of mexiletine, were synthesized and fully characterized. Properties of (R)‐ and (S)‐PHM, in terms of blocking potency and stereoselectivity on frog skeletal muscle Na+ channels, were evaluated. The presence of a hydroxy group on the aryloxy moiety in the 4‐position, as in PHM, reduced potency with respect to mexiletine in reducing INa max. However, PHM showed clear use‐dependent behavior similar to that of mexiletine and, in contrast with what is observed with the parent compound, maintained its stereoselectivity during the use‐dependent block. Chirality 16:72–78, 2004. © 2004 Wiley‐Liss, Inc.
Stereoselectivity in the placental transfer and kinetic disposition of racemic bupivacaine administered to parturients with or without a vasoconstrictor
Authors: Papini Olga , Do Carmo Silva Mathes Ângelo , Pereira Da Cunha Sergio , Lucia Lanchote Vera
Published: January 2004

The aim of the present study was to investigate the stereoselectivity in the kinetic disposition and the transplacental distribution of bupivacaine in term parturients during labor. Maternal age ranged from 18–37 years and fetal gestational age from 37.6–41.5 weeks. Healthy parturients (n = 23) received epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine (group B). Maternal venous blood was sampled at regular intervals until 8 h after drug administration and umbilical venous blood was obtained at delivery. Bupivacaine enantiomers were determined in plasma samples by HPLC using a Chiralcel® OD‐R column and a UV detector. One‐ or two‐compartment models were fitted to data and differences between the (+)‐(R) and (–)‐(S) enantiomers were compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine was evaluated using the unpaired Mann‐Whitney test (P< 0.05). The disposition of bupivacaine in maternal plasma was stereoselective, with higher Vd/f (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and Cl/f (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t1/2β (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being observed for (+)‐(R)‐bupivacaine. The combined administration of epinephrine resulted in higher Vd/f (197.86 vs. 140.60 L for (+)‐(R) and 169.46 vs. 132.81 L for (–)‐(S)) and t1/2β values (4.36 vs. 3.24 h for (+)‐(R) and 4.45 vs. 3.30 h for (–)‐(S)). The transplacental distribution of bupivacaine was stereoselective only when bupivacaine was administered without epinephrine (group B), with a higher cord blood/maternal blood ratio being observed for (–)‐(S)‐bupivacaine (0.40 vs. 0.35). Chirality 16:65–71, 2004. © 2004 Wiley‐Liss, Inc.
Enantioselective reactions of α‐lithiated allyl aryl sulfides using chiral bis(oxazoline)s
Authors: Nakamura Shuichi , Kato Toru , Nishimura Haruka , Toru Takeshi
Published: January 2004

The reaction of α‐lithio allyl aryl sulfides, generated by treatment with n‐BuLi and chiral ligands at −78°C, with ketones was examined. The α‐addition products were formed in preference to the γ‐addition products. The enantioselectivity of the α‐addition products varied depending on the chiral ligand, and bis(oxazoline)‐tBu showed the highest enantioselectivity. Chirality 16:86–89, 2004. © 2004 Wiley‐Liss, Inc.
Allylation and propargylation of chiral cyanopropanoates: An efficient route to long chain α‐substituted α‐methyl α‐amino acids
Authors: Cativiela Carlos , Díaz‐De‐Villegas María D. , Gálvez José A. , Ronco Eva
Published: January 2004

α‐Methyllysine and 2‐amino‐2‐methylundecanoic acid, two α,α‐disubstituted unnatural glycines, were synthesized using highly diastereoselective allylation or propargylation of chiral (1S,2R,4R)‐10‐dicyclohexylsulfamoylisobornyl 2‐cyanopropanoate as the key step to introduce the long side chain. Chirality 16:106–111, 2004. © 2004 Wiley‐Liss, Inc.
2‐(2,3‐Dihydro‐1H‐indol‐3‐yl)ethanol: Synthesis, separation of enantiomers, and assignment of absolute stereochemistry by X‐ray structure analysis
Authors: Frydenvang Karla , Bech Sommer Michael , Heckmann Dieter , Nielsen Ole , Bang‐Andersen Benny
Published: January 2004

The first direct resolution of racemic 2‐(2,3‐dihydro‐lH‐indol‐3‐yl)ethanol—prepared by catalytic hydrogenation of 2‐(lH‐indol‐3‐yl)ethanol—has been accomplished by chiral simulated moving bed (SMB) chromatography. The single enantiomers were isolated as their dihydrogen phosphate salts. Single‐crystal X‐ray analyses were successful, revealing that the (+)‐enantiomer of 2‐(2,3‐dihydro‐lH‐indol‐3‐yl)ethanol has the (S) configuration. Chirality 16:126–130, 2004. © 2004 Wiley‐Liss, Inc.
In vitro release and stereoselective disposition of flurbiprofen loaded to poly(D,L‐lactide‐ co‐glycolide) nanoparticles in rats
Authors: Radwan Mahasen A. , Aboul‐Enein Hassan Y.
Published: January 2004

Flurbiprofen (FL) is a chiral 2‐arylpropionate used clinically as the racemate (rac‐FL). This study was undertaken to investigate the influence of sustained release formulation on the pharmacokinetics of flurbiprofen enantiomers (−) ‐R‐FL and (+)‐S‐FL. Therefore, a stereoselective high‐performance liquid chromatographic (HPLC) method was developed and validated for the rapid, quantitative determination of (−)‐R‐FL and (+)‐S‐FL in rat plasma. Flurbiprofen‐loaded poly(D,L‐lactide‐co‐glycolide) nanoparticles (rac‐FL‐PLGA) were prepared by in emulsion–solvent evaporation technique. Optimum conditions for rac‐FL‐PLGA nanoparticle preparation were considered, and the in vitro release of rac‐FL, R‐FL, and S‐FL were followed up to 48 h in phosphate buffer (pH 7.4). The three tested formulations revealed approximately zero‐order release of either (−)‐R‐FL or S‐FL up to 24 h with r ≥ 0.97.Surprisingly, there was no significant difference between t50% of the three formulations (21.6 ± 1.1 h). The stereoselective disposition of the sustained release rac‐FL deliverv system was investigated in rats. There was a rapid release of R‐FL, S‐FL, or rac‐FL followed by a slower one and Cmax values were observed after 2.5 ± 2.5, 8.3 ± 3.4 and 8.86 ± 3.6 h of (−)‐R‐FL, (+)‐S‐FL, and rac‐FL, respectively, after nanoparticle administration. PLGA nanoparticles increased the mean retention time (MRT) of S‐FL by 2.7‐fold, from 6.8 to 16.3 h, compared to rac‐FL. Although the dose of rac‐FL‐PLGA nanoparticles was only 2.5 times higher than that of the drug in the suspension, the mean (+)‐S‐FL concentration after 12 h was 3.4 times higher in the case of nanoparticles than after the free form, 10.35 ± 1.6 and 3.04 ± 1.1 mg/l, respectively. The area under the concentration‐time curve (AUC) values of (+)‐S‐FL and rac‐FL were about 2.5‐fold higher after the nanoparticles compared to suspension, while the AUC of the (−)‐R‐FL was about 3.5 times higher. This difference may indicate that the two enantiomers have different absorption kinetics. The present study provides evidence that the sorption of racemic flurbiprofen to PLGA nanoparticles was successful in maintaining (at least up to 12 h) elevated plasma drug concentrations of (+)‐S‐FL in rats. Chirality 16:119–125, 2004. © 2004 Wiley‐Liss, Inc.
Chiral symmetry‐breaking transition in growth front of crystal phase of 1,1′‐binaphthyl in its supercooled melt
Authors: Asakura Kouichi , Nagasaka Yasushi , Hidaka Masashi , Hayashi Masato , Osanai Shuichi , Kondepudi Dilip K.
Published: January 2004

Although the theory of spontaneous chiral symmetry‐breaking in open systems was proposed some time ago, experimental realization of this phenomenon has not been achieved. In this article, we note that the crystal growth front of 1,1′‐binaphthyl shows many of the characteristics of an open system in which chiral symmetry‐breaking has occurred. We studied the temperature profiles of the crystallizing surface and obtained X‐ray diffraction data of the crystals grown from the melt under controlled conditions. The data show that, under appropriate conditions, the observed bimodal probability distribution of enantiomeric excess (ee) with maxima ∼60% is due exclusively to chiral crystals and not due to racemic crystals of 1,1′‐binaphthyl that can also form at large supercooling. The mass independence of the ee shows that the growing front maintains a constant ee, which is a clear signature of open systems in steady state. Chirality 16:131–136, 2004. © 2004 Wiley‐Liss, Inc.
Pharmacokinetics of the enantiomers of trans‐tramadol and its active metabolite, trans‐O‐demethyltramadol, in healthy male and female chinese volunteers
Authors: Hui‐chen Liu , Yang Yu , Na Wang , Ming Deng , Jian‐fang Liu , Hong‐yuan Xue
Published: January 2004

By using a high‐performance capillary electrophoresis method, the pharmacokinetics of the enantiomers of trans‐tramadol (trans‐T) and its active metabolite, trans‐O‐demethyltramadol (M1), was studied in healthy male and female Chinese volunteers after oral administration of 100 mg trans‐T hydrochloride. The values of Cmax for the enantiomers of trans‐T and M1, and AUC0–∞ for (–)‐trans T, (+)‐M1, and (–)‐M1 were higher in females than in males. The values of Vd/F for the enantiomers of trans‐T and CLr for (+)‐M1 were lower in females than in males. The value of t1/2 for (–)‐M1 was longer in females than in males. There were significant differences in pharmacokinetic parameters of the two enantiomers of trans‐T or M1 both in males and in females. The (+)/(–)‐enantiomeric ratios of tmax, Vd/F for trans‐T in males were significantly different from those in females and the (+)/(–)‐enantiomeric ratios of pharmacokinetic parameters for M1 in males were similar to those in females. There are gender‐related differences in the pharmacokinetics of the enantiomers of trans‐T and M1 which may be due to the greater body weights for men and/or the higher CYP2D6 activity in women. The pharmacokinetics of trans‐T and M1 is stereoselective in men and women. There is a gender‐related difference in the stereoselectivity in pharmacokinetics of trans‐T in human and the stereoselectivity in pharmacokinetics of M1 in men is similar to that in women. Chirality 16:112–118, 2004. © 2004 Wiley‐Liss, Inc.
“Viele Köche verderben den Brei” – H.Koch, H. P. G.Koch, K.Koch, W.Kochund W. D. J.Kochals Gefäßpflanzen‐Autoren in europäischen Basisfloren und Standardlisten
Authors: Raus Th.
Published: December 2003

Bei Namen von Gefäßpflanzentaxa mit bibliographischem Zitat wird die AutorbezeichnungKochin hohem Maße unklar und verwirrend verwendet. Rund 67 % von 1121 in fünf zeitgenössischen Basisfloren und Standardlisten exemplarisch nachgeprüftenKoch‐Zitaten entsprechen nicht dem empfohlenen internationalen Standard des Autorenlexikons vonBrummitt&Powell(Authors of Plant Names, Kew 1992). Zahlreiche Taxa werden dadurch scheinbar, einige tatsächlich nicht dem zutreffenden Beschreiber bzw. Kombinationsautor zugeschrieben. In tabellarischer Form werden Hilfen zur Überprüfung unkritischerKoch‐Zitate geboten.
Seedling diversity in Araceae and its systematic implications
Authors: Tillich H.‐J.
Published: December 2003

The paper gives a detailed morphological analysis of seedlings of 45 genera of Araceae. Including all seedling descriptions in the literature, informations for 60 genera are available now.

Generally, the cotyledon is subdivided into a bifacial hypophyll and a unifacial hyperphyll. The presumably most ancestral seedling type is characterised by a compact cotyledon, the cotyledonary hyperphyll is a haustorium inside the copious endosperm. Furthermore, it has a well growing primary root, the plumule gives rise to one to several cataphylls until the first eophylls develop. Starting from this type, two very different evolutionary lines can be followed. The first one leads to a seedling of which the cotyledonary hypophyll is transformed to an assimilating, blade‐like organ, while the minute unifacial hyperphyll is haustorial and hidden in the seed (e.g. Philodendron, Colocasia, Sauromatum ). The second line leads to endospermless seeds, the cotyledonary hyperphyll is transformed to a voluminous storage organ, hypocotyl and primary root are completely missing (e.g. Aglaonema, Arophyton, Nephthytis ). Many tribes are characterised by one or by two closely related seedling types, but a few tribes encompass a surprising diversity of seedlings (e. g. Caladieae, Spathicarpeae, Areae). The possible adaptive value of different seedlings is discussed.
Vegetationskundliche Untersuchungen im Dornod Aimak (Ost‐Aimak) der Mongolei
Authors: Hilbig W.
Published: December 2003

Während einer im Sommer 2002 durchgeführten botanischen Exkursion in den Dornod Aimak (Ost‐Aimak) der Mongolei wurden in den pflanzengeographischen Bezirken Ostmongolei und Chingan‐Vorgebirge Vegetationsuntersuchungen durchgeführt.

Vor allem den weitverbreiteten Steppen und Wiesensteppen, den Ulmen‐Buschwäldern mit Paeonio‐lactiflorae‐Ulmetum pumilae ass. nov., Dünenkiefernwäldern, Spiraea‐, Cotoneaster‐ und Armeniaca‐ Gebüschen und der Salzvegetation wurde Aufmerksamkeit geschenkt. Aber auch Weidengebüsche, Weiderasen und Wiesen sowie Hochstaudenbestände, Röhrichte und andere Pflanzenbestände der Flussauen wurden wie die Ruderalbestände der Siedlungen in die Beobachtungen und Untersuchungen einbezogen.

Als Besonderheit der Gehölzvegetation konnte in einer kleinen Schlucht im Chingan‐Vorgebirge ein Laubwaldvorkommen mit Padus avium und Malus baccata erfasst werden. Auf die Beziehungen der angetroffenen Pflanzengesellschaften zu entsprechenden Beständen in der chinesischen Barga und der Inneren Mongolei wird hingewiesen.
Plant distribution patterns in Germany – Will aliens match natives?
Authors: Kühn I. , Brandl R. , May R. , Klotz St.
Published: December 2003

Using data on the distribution of the German vascular flora and a wide selection of environmental data we address questions regarding native and alien plant distribution patterns. We found highly significant positive relationships between plant species richness of natives and aliens on three spatial scales (c. 100 km2, c. 1,000 km2, c. 10,000 km2). Given the results of major axis regressions on log‐transformed data, we conclude that alien species richness increases overproportionately compared to native species richness. To determine common factors for plant richness patterns, we used a principal component analysis (PCA) to reduce the number of environmental variables. The principal components were used in a multiple regression as independent variables to model plant species richness of aliens and natives, corrected for spatial autocorrelation. The diversity of geological substrates is considered most important for native and alien plant species richness. Furthermore, area of loess subsoils is important for archaeophyte richness, urbanisation is important for neophyte richness.

Comparisons of similarity matrices between natives and aliens using standardised similarities as well as Simpsons similarities of randomly selected grid cells showed a positive correlation. Similarity patterns provided by native plant species are traced by archaeophytes but not followed by neophytes. Similarities of archaeophytes were significantly higher than those of natives whereas similarities of neophytes where significantly lower than those of natives. Therefore, we concluded that archaeophytes lead to homogenisation of the German flora but are mainly plants of arable fields that are homogeneous due to human land use. Neophytes, however, did not lead to homogenisation but increase local biodiversity.
Patterns of species composition and species richness in most (ash‐alder) forests of northern Germany (Schleswig‐Holstein)
Authors: Härdtle W. , von Oheimb G. , Meyer H. , Westphal Chr.
Published: December 2003

In this study we analysed the relationships between the species composition/richness of moist forests and environmental variables (light conditions, soil pH, S‐value, base saturation, C/N‐ratio, lime content, soil moisture, thickness of A‐ and Gr‐horizons) on the basis of 38 soil sample plots (northern Germany, Schleswig‐Holstein) and a principal component analysis. In addition, we tried to explain the species richness of moist forests in the context of the species pool hypothesis by comparing the local species richness with the regional species pool.

Taking moist forests as an example our results confirm the findings of other studies that the species richness of basiphilous forest communities is due to the great number of basiphilous species in the Central European forest flora. In deciduous forests in northern Germany in general the species richness increases with increasing base supply. However, particularly in moist forests the species composition/richness is affected mainly by the soil moisture, as this site parameter is responsible for a certain site heterogeneity and niche availability, and therefore often masks the influence of other site factors. The lime content in the subsoil and the base supply are of subordinate importance for the species composition and are little (negatively) or not correlated with the species richness, respectively. Light conditions and the C/N‐ratio have almost no influence on the species richness. The results present evidence in favour of the species pool hypothesis.
Vom Minnesang in der Datenbank
Authors: Schlechter Armin , Zimmermann Karin , Miller Matthias
Published: December 2003

Die mittelalterlichen deutschen Handschriften der Universitätsbibliothek Heidelberg sind kulturhistorische Zeugnisse von Rang. Durch umfassende Katalogisierung wird die Sammlung für die Forschung neu erschlossen
Vom Ursprung des Sonnensystems
Authors: Többe Sandra
Published: December 2003

Der Mineraloge und Kosmochemiker Andreas Pack
Der Kampf gegen die Retroviren
Authors: Schumann Gerald G.
Published: December 2003

Ein gentherapeutischer Ansatz zur Behandlung von Virusinfektionen setzt auf eingeschleuste Enzyme, um den Lebenszyklus der Viren von innen zu zerstören
Stimulation für die Klinische Forschung
Authors: Dichgans Johannes
Published: December 2003

Mit einem neuen Förderprogramm sollen Defizite in der Gesundheitsforschung abgebaut werden — DFG und BMBF starten „Klinische Studien”︁
Elderly suicide attempters with depression are often diagnosed only after the attempt
Authors: Suominen Kirsi , Isometsä Erkki , Lönnqvist Jouko
Published: January 2004

Objective

No previous study has comprehensively investigated the pattern of health care contacts among elderly subjects attempting suicide. The present study compared elderly suicide attempters with younger attempters, before and after attempted suicide, in terms of health care contacts, clinical diagnoses of mental disorders, and characteristics predicting lack of treatment contact after the index attempt.

Methods

All consecutive 1198 suicide attempters treated in hospital emergency rooms in Helsinki, Finland, from 15.1.1997 to 14.1.1998 were identified and divided into two age groups: (1) elderly suicide attempters aged 60 years or more (n = 81) and (2) suicide attempters aged under 60 years (n = 1117).

Results

During the final 12 months before the attempt, the majority of elderly suicide attempters had a contact with primary health care, but their mood disorders were likely to have remained undiagnosed before the index attempt. In primary health care, only 4% had been diagnosed with a mood disorder before the attempt, but 57% after (p < 0.001). After the suicide attempt, most elderly suicide attempters were referred for aftercare, two thirds having contact with psychiatric care.

Conclusions

For purposes of preventing suicidal behaviour, screening for depression, plus further education on recognition, diagnosis and treatment of mood disorders among the elderly in primary health care setting are needed. Copyright © 2004 John Wiley & Sons, Ltd.
Cross‐national comparison and validation of the Alzheimer's Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO‐HARPID)
Authors: Verhey Frans R. , Houx Peter , van Lang Natascha , Huppert Felicia , Stoppe Gabriella , Saerens Jos , Böhm Peter , de Vreese Luc , Nordlund Arto , DeDeyn Peter P. , Neri Mirco , Peña‐Casanova Jordi , Wallin Anders , Bollen Eduard , Middelkoop Huub , Nargeot Marie‐Christine , Puel Michèle , Fleischmann Ulrich M. , Jolles Jellemer
Published: January 2004

Background

The Alzheimer's Disease Assessment Scale (ADAS) is often used in international multicenter trials. Use across countries presupposes correct translation and adaptation of the scale, and maintenance of its psychometric properties.

Objectives

To compare the various translations of the ADAS used in Western Europe, to design internationally harmonized translations and to validate these.

Setting

International cooperative study in eight European countries.

Methods

An inventory was made of existing versions of the ADAS‐Cog used in eight European countries, and adaptations were made. The concurrent validity of the harmonized versions of the ADAS was tested in 283 patients with probable or possible Alzheimer's disease. The Nurses Observation Scale for Geriatrics (NOSGER), CAMCOG‐R and MMSE was used to assess concordance between cognitive and behavioral measures.

Results

Differences between the versions mainly involved object naming, items for verbal memory, such as the number of trials allowed, the imagery value of the words selected as targets or distractors, and the number of parallel versions. These differences were eliminated by adapting and harmonizing the various versions of the ADAS‐Cog. Thereafter, only small differences between the different countries were found, and patterns of correlation between ADAS‐Cog, and the NOSGER, CAMCOG‐R and MMSE were consistent.

Conclusions

The study underlines the need to use harmonized versions of instruments for rating dementia in multinational studies. The findings indicate that the harmonization of the ADAS‐Cog was successful. Copyright © 2004 John Wiley & Sons, Ltd.
A multinational, randomised, 12‐week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer's disease
Authors: Jones Roy W. , Soininen Hilkka , Hager Klaus , Aarsland Dag , Passmore Peter , Murthy Anita , Zhang Richard , Bahra Ranbir
Published: January 2004

Objectives

To compare directly, in the same patient cohort, the ease of use and tolerability of donepezil and galantamine in the treatment of Alzheimer's disease (AD), and investigate the effects of both treatments on cognition and activities of daily living (ADL).

Methods

Patients with mild to moderate AD from 14 European centres were randomised to receive open‐label donepezil (up to 10 mg once daily) or galantamine (up to 12 mg twice daily) for 12 weeks, according to the approved product labelling. Physicians and caregivers completed questionnaires rating satisfaction with treatment/ease of use in daily practice. Secondary assessments were the ADAS‐cog, the MMSE, and the DAD scale to assess ADL. Tolerability was evaluated by reporting adverse events (AEs).

Results

Both physicians and caregivers reported significantly greater overall satisfaction/ease of use for donepezil (n = 64) compared with galantamine (n = 56) at weeks 4, 12, and endpoint (week 12 LOCF; all p‐values <0.05). Significantly greater improvements in cognition were also observed for donepezil versus galantamine on the ADAS‐cog at Week 12 and endpoint (p‐values <0.05). ADL improved significantly in the donepezil group compared with the galantamine group at weeks 4, 12, and endpoint (p‐values <0.05). Most AEs were mild to moderate, however, 46% galantamine‐treated patients reported gastrointestinal AEs vs 25% donepezil patients.

Conclusions

Physician and caregiver ease of use/satisfaction scores, and assessments of cognition and ADL, showed significant benefits for donepezil compared with galantamine in this direct comparative trial. Both treatments were well tolerated, with more gastrointestinal AEs reported for galantamine vs donepezil. Copyright © 2004 John Wiley & Sons, Ltd.
Obesity and depressive symptoms in Chinese elderly
Authors: Bin Li Zhi , Yin Ho Sai , Man Chan Wai , Sang Ho Kin , Pik Li Mun , Leung Gabriel M , Hing Lam Tai
Published: January 2004

Objectives

The main objective was to examine the association between obesity and depressive symptoms among Chinese elderly in Hong Kong.

Methods

Cross‐sectional data on depressive symptoms and body mass index from 56 167 clients aged 65 or over who enrolled as members of Elderly Health Centres from July 1998 to December 2000 were analysed using multiple logistic regression with adjustment of potential confounders.

Results

Among 18 750 men and 37 417 women, the prevalence [95% confidence interval (CI)] of depressive symptoms (based on the Geriatric Depression Scale) was 4.9% (4.6–5.2%) and 7.9% (7.6–8.1%) respectively (p < 0.001). The prevalence of obesity (by World Health Organisation Asian standard: body mass index ≥25.0) in women was significantly higher than that of men (42.1% (41.6–42.7%) vs 36.6% (35.9–37.3%), p < 0.001). Obese men and women were about 20% less likely to suffer from depressive symptoms compared with those with normal weight after adjustment for confounders, with odds ratios (95% CI) of 0.82 (0.69–0.97) and 0.78 (0.71–0.86) respectively. Negative linear trends were observed between depressive symptoms and BMI categories in both sexes, and women showed a greater slope and stronger statistical significance than men.

Conclusions

Both obese elderly men and women in Hong Kong were less likely to suffer from depressive symptoms than those of normal weight. The results support the ‘jolly fat’ hypothesis previously restricted to men, and extend the hypothesis to female elderly. Chinese traditional culture and positive values towards obesity may be protective against depressive symptoms. Copyright © 2004 John Wiley & Sons, Ltd.
Validity of the Telephone Interview for Cognitive Status (TICS) in post‐stroke subjects
Authors: Barber Mark , Stott David J.
Published: January 2004

Background

Cognitive impairment and dementia are very common after stroke. Telephone screening has potential advantages for clinical follow‐up and population‐based research in this group. We wished to test the validity of the Telephone Interview for Cognitive Status (TICS) for cognitive testing in post‐stroke subjects.

Methods

Cognitive function in stroke outpatients was assessed using the R‐CAMCOG (a modification of the cognitive part of the Cambridge Examination for Mental Disorders of the Elderly, for use in stroke subjects) along with the TICS and a modified version, the TICSm. The tests were administered in random order. A cut‐off point of 33 on the R‐CAMCOG was used to define post‐stroke dementia.

Results

Sixty‐four patients with a median age of 72 years were assessed. The Pearson correlation coefficients between the R‐CAMCOG and the TICS and TICSm were 0.833 and 0.855 (both p <0.001) respectively. Twenty‐four (38%) patients met R‐CAMCOG criteria for post‐stroke dementia. The area under the ROC curve for both the TICS and TICSm was 0.94. Using a cut‐off of 28 or less on the TICS produced a sensitivity of 88% and a specificity of 85% for the diagnosis of post‐stroke dementia. For the TICSm a cut‐off of 20 or lower produced a sensitivity of 92% and a specificity of 80%.

Conclusions

The TICS and TICSm telephone questionnaires are practicable and valid methods of assessing cognitive function in community outpatients following stroke. Scores of ≤28 and ≤20 respectively carry good sensitivity and specificity for the diagnosis of post‐stroke dementia. Copyright © 2004 John Wiley & Sons, Ltd.
Syntheses and biological activities of S‐1,2,4‐triazolo(1,5‐a)pyrimidinylalkyl dithiophosphates
Authors: Chen Wen‐Bin , Jin Gui‐Yu
Published: January 2004

We introduced dithiophosphate moieties into the fused heterocyclic compound to prepare the title derivatives and characterized their structures by elemental analysis, 1H NMR, and IR spectral data. We found that these compounds show good fungicidal and herbicidal activities and good plant growth regulation activity. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:607–611, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10198
Pyridazine, oxazine, pyrrole, and pyrrolo[1,2‐a]quinazoline derivatives from malononitrile dimer
Authors: Eldin Abdellatif M. Salah
Published: January 2004

2‐Amino‐1,1,3‐tricyano‐3‐bromopropene was obtained from bromination of 2‐amino‐1,1,3‐tricyanopropene (malononitrile dimer) with N‐bromosuccinimide. This bromo derivative reacts with hydrazine hydrate, phenyl hydrazine, and hydroxylamine hydrochloride to afford pyridazine and oxazine derivatives, respectively. In base‐catalyzed reactions with primary aromatic amines and anthranilic acid derivatives, it produces N‐aryl pyrrol‐3,5‐dicarbonitrile and pyrrolo[1,2‐a]quinazolin‐5‐imine, or pyrrolo[1,2‐a]quinazolin‐5‐one derivatives, respectively. The structures of the newly synthesized heterocycles were established on the basis of elemental analyses and spectral data. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:612–616, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10199
A convenient synthesis of diacyl sulfides using a novel sulfur transfer reagent
Authors: Koketsu Mamoru , Sekiya Yoji , Ishihara Hideharu
Published: January 2004

Various diacyl sulfides were synthesized by reaction of acyl chlorides with LiAlHSH. Reaction of glutaryl chloride with LiAlHSH afforded glutaric thioanhydride. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:633–635, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10217
Indole‐Diterpene Synthetic Studies: Total Synthesis of (−)‐21‐Isopentenylpaxilline
Authors: Smith Amos B. , Cui Haifeng
Published: December 2003

An efficient, stereocontrolled total synthesis of the complex indole‐diterpene alkaloid (−)‐21‐isopentenylpaxilline (1) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (−)‐68, involving a highly efficient union of the eastern and western fragments (−)‐68 and 5 exploiting our 2‐substituted indole synthesis, application of the Negishi π cycloalkylation tactic as a new, potentially general protocol for the construction of ring C, and the fragmentation of a β,γ‐epoxy ketone to introduce the tertiary OH group at C(13) in the indole diterpene skeleton.
Mechanism and Control in Biological Amine Methylation
Authors: Blackburn G. Michael , Gamblin Steven J. , Wilson Jonathan R.
Published: December 2003

Biological methylation is a subject that has fascinated mechanistically minded chemists for over 50 years. While early studies were usually directed at C‐methylation in natural products, more recent work on N‐methylation in DNA and proteins is being supported by the results of X‐ray crystallography. From this source, significant mechanistic detail can be gleaned and powerful insights gained into the nature of enzyme catalysis and selectivity in methyl‐transfer processes. The case of the human histone H3 transmethylase SET7/9 is considered in detail and compared to cognate histone lysine methylases. It provides an analysis of Nature's solution to the task of avoiding over‐methylation.
On the Formation of 2‐Sulfonylbenzo[a]heptalene‐1,3‐diols as Precursors for the Synthesis of Colchicinoids
Authors: Abou‐Hadeed Khaled , Hansen Hans‐Jürgen
Published: December 2003

The benzo[a]heptalene formation from 4‐[(R‐sulfonyl)acetyl]heptalene‐5‐carboxylates 15 and 5‐[(R‐sulfonyl)acetyl]heptalene‐4‐carboxylates 16 (R=Ph or morpholino) in the presence of R′SO2CH2Li and BuLi has been investigated (Scheme 6). Only the sulfonyl moiety linked to the CO group at C(4) of the heptalene skeleton is found at C(3) of the formed benzo[a]heptalene‐2,4‐diols 3 in accordance with the general mechanism of their formation (Scheme 3). Intermediates that might rearrange to corresponding 2‐sulfonylbenzo[a]heptalene‐1,3‐diols lose HO− under the reaction conditions to yield the corresponding cyclopenta[d]heptalenones of type 11 (Schemes 6 and 7). However, the presence of an additional Me group at C(α) of the lithioalkyl sulfones suppresses the loss of HO−, and 4‐methyl‐2‐sulfonylbenzo[a]heptalene‐1,3‐diols of type 4c have been isolated and characterized for the first time (Schemes 8 and 10). A number of X‐ray crystal‐structure analyses of starting materials and of the new benzo[a]heptalenes have been performed. Finally, benzo[a]heptalene 4c has been transformed into its 1,2,3‐trimethoxy derivative 23, a benzo[a]heptalene with the colchicinoid substitution pattern at ring A (Scheme 11).
Parity‐Violating Potentials for the Torsional Motion of Methanol (CH3OH) and Its Isotopomers (CD3OH, 13CH3OH, CH3OD, CH3OT, CHD2OH, and CHDTOH)
Authors: Berger Robert , Quack Martin , Sieben Achim , Willeke Martin
Published: December 2003

We present calculations on the parity‐conserving and the parity‐violating potentials in several MeOH isotopomers for the torsional motion by the newly developed methods of electroweak quantum chemistry from our group. The absolute magnitudes of the parity‐violating potentials for MeOH are small compared to H2O2 and C2H4, but similar to C2H6, which is explained by the high (threefold) symmetry of the torsional top in MeOH and C2H6. ‘Chiral’ and ‘achiral’ isotopic substitutions in MeOH lead to small changes only, but vibrational averaging is discussed to be important in all these cases. Simple isotopic sum rules are derived to explain and predict the relationships between parity‐violating potentials in various conformations and configurations of the several isotopomers investigated. The parity‐violating energy difference ΔpvE=Epv(R)−Epv(S) between the enantiomers of chiral CHDTOH, first synthesized by Arigoni and co‐workers, is for two conformers ca. −3.66⋅10−17 and for the third one +7.32⋅10−17 hc cm−1. Thus, for ΔpvE, the conformation is more important than the configuration (at the equilibrium geometries, without vibrational averaging). Averaging over torsional tunneling may lead to further cancellation and even smaller values.
Preparation of (S,S)‐Fmoc‐β2hIle‐OH, (S)‐Fmoc‐β2hMet‐OH, and (S)‐Fmoc‐β2hTyr(tBu)‐OH for Solid‐Phase Syntheses of β2‐ and β2/β3‐Peptides
Authors: Sebesta Radovan , Seebach Dieter
Published: December 2003

The preparation of three new N‐Fmoc‐protected (Fmoc=[(9H‐fluoren‐9‐yl)methoxy]carbonyl) β2‐homoamino acids with proteinogenic side chains (from Ile, Tyr, and Met) is described, the key step being a diastereoselective amidomethylation of the corresponding Ti‐enolates of 3‐acyl‐4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐ones with CbzNHCH2OMe/TiCl4 (Cbz=(benzyloxy)carbonyl) in yields of 60–70% and with diastereoselectivities of >90%. Removal of the chiral auxiliary with LiOH or NaOH gives the N‐Cbz‐protected β‐amino acids, which were subjected to an N‐Cbz/N‐Fmoc (Fmoc=[(9H‐fluoren‐9‐yl)methoxy]carbonyl) protective‐group exchange. The method is suitable for large‐scale preparation of Fmoc‐β2hXaa‐OH for solid‐phase syntheses of β‐peptides. The Fmoc‐amino acids and all compounds leading to them have been fully characterized by melting points, optical rotations, IR, 1H‐ and 13C‐NMR, and mass spectra, as well as by elemental analyses.
Synthesis of a Derivative of the Peptaibol‐Antibiotic Trichovirin I 1B by Means of the ‘Azirine/Oxazolone Method’
Authors: Luykx Roeland T. N. , Linden Anthony , Heimgartner Heinz
Published: December 2003

According to the earlier published synthesis of the C‐terminal nonapeptide of Trichovirin I 1B, Z‐Ser(tBu)‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (5), the complete tetradecapeptide Z‐Aib‐Asn(Trt)‐Leu‐Aib‐Pro‐Ser(tBu)‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (11b), a protected Trichovirin I 1B, has now been prepared by means of the ‘azirine/oxazolone method’. With the exception of the N‐terminal Aib(1), all Aib residues were introduced by the coupling of the corresponding amino or peptide acids with 2,2‐dimethyl‐2H‐azirine‐3‐(N‐methyl‐N‐phenylamine) (1a) and methyl N‐(2,2‐dimethyl‐2H‐azirin‐3‐yl)‐L‐prolinate (3a) as the Aib and Aib‐Pro synthons, respectively. Single crystals of two segments, i.e., the N‐terminal hexapeptide Z‐Aib‐Asn(Trt)‐Leu‐Aib‐Pro‐Ser(tBu)‐OMe (23) and the C‐terminal octapeptide Z‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (17), were obtained and their structures have been established by X‐ray crystallography. Following the same strategy, the C‐terminal nonapeptide of Trichovirin I 4A, Z‐Ala‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (26), was also synthesized and characterized by X‐ray crystallography.
Outlying Charge, Stability, Efficiency, and Algorithmic Enhancements in the Quantum‐Mechanical Solvation Method, COSab‐GAMESS
Authors: Gregerson Laura N. , Baldridge Kim K.
Published: December 2003

In this work, we present algorithmic modifications and extensions to our quantum‐mechanical approach for the inclusion of solvent effects by means of molecule‐shaped cavities. The theory of conductor‐like screening, modified and extended for quantum‐mechanical techniques, serves as the basis for our solvation methodology. The modified method is being referred to as COSab‐GAMESS and is available within the GAMESS package. Our previous work has emphasized the implementation of this model by way of a distributed multipole approach for handling the effects of outlying charge. The method has been enabled within the framework of open‐ and closed‐shell RHF and MP2. In the present work, we present a) a second method to handle outlying charge effects, b) algorithmic extensions to open‐ and closed‐shell density‐functional theory, second‐derivative analysis, and reaction‐path following, and c) enhancements to improve performance, convergence, and predictability. The method is now surtable for large molecular systems. New features of the enhanced continuum model are highlighted by means of a set of neutral and charged species. Computations on a series of structures with roughly the same molecular shape and volume provides an evaluation of cavitation effects.
Ab Initio Structure/Reactivity Investigations of Illudin‐Based Antitumor Agents: A Model for Reaction in vivo
Authors: Gregerson Laura N. , McMorris Trevor C. , Siegel Jay S. , Baldridge Kim K.
Published: December 2003

(Hydroxymethyl)acylfulvene (HMAF, irofulven; 4), a third‐generation derivative of a natural product extracted from the mushroom Omphalotus illudens, is selectively toxic towards certain forms of malignant tumors. Conversion of HMAF and cognates to stable aromatic derivatives is triggered by thiol attack in vitro and in vivo. Quantum‐chemical methods predict well the structure for several functionalized derivatives of irofulven as compared to known X‐ray crystallographic structures. Computational reaction profiles for thiol attack and aromatic rearrangement of irofulven and illudin S, a toxin from which irofulven is derived, provide insight into HMAF's selectivity and toxicity. Methods used include hybrid density‐functional theory (HDFT), HartreeFock (HF), and MøllerPlesset second‐order perturbation theory (MP2). Solvent effects have been explored by means of the new continuum‐solvation method, COSab, presented in an accompanying paper.
Synthesis, CD Spectra, and Enzymatic Stability of β2‐Oligoazapeptides Prepared from (S)‐2‐Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and Leu
Authors: Lelais Gérald , Seebach Dieter
Published: December 2003

β‐Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs. 1 and 2). We report here the synthesis and spectroscopic investigations of β2‐peptide analogs consisting of (S)‐3‐aza‐β‐amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N‐benzyl‐L‐α‐amino acids with an oxaziridine (Scheme 1). Couplings and fragment coupling of the 3‐benzylaza‐β2‐amino acids and a corresponding tripeptide (N‐Boc/C‐OMe strategy) with common peptide‐coupling reagents in solution led to β2‐di, β2‐tri‐, and β2‐hexaazapeptide derivatives, which could be N‐debenzylated (4–9; Schemes 2–4). The new compounds were identified by optical rotation, and IR, 1H‐ and 13C‐NMR, and CD spectroscopy (Figs. 4 and 5) and high‐resolution mass spectrometry, and, in one case, by X‐ray crystallography (Fig. 3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of the β2‐azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N‐Boc and C‐OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)‐314‐helical structure. The N‐Boc‐β2‐tri and N‐Boc‐β2‐hexaazapeptide esters, 7 and 9, were shown to be stable for 48 h against the following peptidases: pronase, proteinase K, chymotrypsin, trypsin, carboxypeptidase A, and 20S proteasome.
New Chromium Enolates
Authors: Kündig E. Peter , Bernardinelli Gérald , Kondratenko Mikhail , Robvieux Fabrice , Romanens Patrick
Published: December 2003

Three new (η2‐acrylate)(η6‐arene)dicarbonylchromium complexes are reported. They were obtained either by CO/acrylate exchange in [Cr(η6‐benzene)(CO)3] (1) via the photolytically generated η2‐cyclooctene intermediate or by arene exchange in [Cr(η2‐methyl acrylate)(η6‐benzene)(CO)2] (3) (Scheme 1). On crystallization, [Cr(η2‐methyl acrylate)(η6‐o‐xylene)(CO)2] (5) underwent partial resolution. The degree of this resolution was analyzed via X‐ray crystal‐structure determination (Fig. 1) and was correlated to the CD spectra in solution (Fig. 6), thus allowing the assignment of the absolute configuration. The reaction of [Cr(η2‐acrylate)(η6‐benzene)(CO)2] complexes with cyclopentad‐1,3‐diene or 1H‐indene afforded new (η6‐cyclopenta‐2,4‐dien‐1‐yl)‐ or (η6‐1H‐inden‐1‐yl)(η3‐oxaallyl)chromium complexes (Scheme 2). A mechanism is proposed that involves arene‐ligand substitution by the diene ligand, initiated by haptotropic rearrangement of the acrylate from a η2‐ to a η4‐coordination mode, followed by hydride migration from the diene to the acrylate (Scheme 3). An X‐ray crystal‐structure determination of [Cr(CO)2(η5‐1H‐inden‐1‐yl){η3‐CH(CH2CF3)C(O)OEt}] (8) reveals a metal enolate that is best described as η3‐oxaallyl species (Fig. 2). A shorter, more‐efficient route to the [Cr(η5‐1H‐inden‐1‐yl)(η3‐oxaallyl)] complexes was devised via the reaction of [Cr(CO)2(η2‐cyclooctene)(η6‐1H‐indene)] with methyl acrylate (Scheme 4).
Stereochemical Course of the Formation of the C(7)‐Formyl Group from a Chiral Methyl Group during the Transformation of Chlorophyllide a into Chlorophyllide b
Authors: Shoolingin‐Jordan Peter M. , Williams Stephen C.
Published: December 2003

The biosynthesis of chlorophyll a and chlorophyll b from (2R,3R)‐ and (2S,3S)‐5‐amino[2,3‐14C2,2,3‐2H2,2,3‐3H2]levulinic acid in greening barley has established that chlorophyllide a oxidase catalyses the transformation of the methyl group at C(7) of chlorophyllide a into the CHO group of chlorophyllide b with the loss of HSi from the 7‐(hydroxymethyl)chlorophyllide intermediate.
Building [2]Catenanes around a Tris(diimine)ruthenium(2+) ([Ru(diimine)3]2+) Complex Core Used as Template
Authors: Mobian Pierre , Kern Jean‐Marc , Sauvage Jean‐Pierre
Published: December 2003

In the course of the last two decades, the use of transition metals as templates for constructing catenanes has almost exclusively been restricted to tetrahedral copper(I). The present work is dealing with an octahedral metal, ruthenium(II), coordinated to three bidentate chelates. Incorporation of two chelates (1,10‐phenanthroline) in a ring allows to prepare a C2‐symmetric ruthenium complex, the two chelates being disposed cis to one another (see 142+ and 162+ in Scheme 5 and 6, resp.). The ring is large enough to accomodate a third chelate, thus allowing the metal‐directed threading of a long fragment containing the third chelate (2,2′‐bipyridine derivative; see 232+ and 242+ in Scheme 8). The last step consists of a ring‐closing metathesis reaction with two terminal olefins. The two ruthenium(II)‐complexed catenanes 252+ and 262+ were prepared by using this strategy, each containing a 42‐membered ring interlocked to a larger macrocycle (50‐ or 63‐membered ring) incorporating the two 1,10‐phenanthroline chelates. It is expected that these catenanes can be set in motion under light‐irradiation, thus behaving as photochemically driven molecular machines.
On Penicillin‐Binding Protein 1b Affinity‐Labeling Reagents
Authors: Volke Daniela , Daghish Mohammed , Hennig Lothar , Findeisen Matthias , Giesa Sabine , Oehme Ramona , Welzel Peter
Published: December 2003

The synthesis of some 3‐aryl‐3‐(trifluoromethyl)3H‐diazirine and benzophenone‐based photoaffinity labels is reported. The photolabile group is bound to a scaffold that also accommodates functional groups to which an indicator unit (biotin) and the bioactive ligand can be attached orthogonally. To three of the labels, moenomycin was conjugated with the aim to provide tools for the identification of the moenomycin binding site within the transglycosylase domain of the enzyme PBP 1b. Some preliminary photoaffinity‐labeling experiments were carried out.
Derivatives of Coenzyme F430 with a Covalently Attached α‐Axial Ligand. Part I
Authors: Bauer Carsten , Jaun Bernhard
Published: December 2003

X‐Ray structures of the enzyme methyl‐coenzyme M reductase show that the Ni‐center in the prosthetic group coenzyme F430 is penta‐ or hexacoordinated with the carboxamide group of a glutamine residue occupying the axial coordination site on the α‐side of the macrocycle. To obtain diastereoselectively coordinated complexes for mechanistic and spectroscopic studies of the free coenzyme in solution, we aimed to prepare partial‐synthetic derivatives of coenzyme F430 that have a coordinating group attached via a linker to one of the propanoic acid side chains. By using molecular‐mechanics calculations and two different conformational search methods, a set of 50 structures containing imidazole or pyridine units as potential ligands were computationally tested according to geometric criteria defining coordinating conformations. The best candidates proved to be proline‐containing tri‐ and tetrapeptides with a methyl‐histidine as the C‐terminal residue. These linkers were synthesized, and their conformation was determined by NMR. Refinement of the molecular modeling by using the experimentally determined geometric restraints allowed us to decide that the tripeptide Pro‐Pro‐His(π‐Me)‐OMe (10) was the most promising of all tested structures for attachment to the side chain at C(3) or C(13) of F430.