Iron(III) and iron(II) complexes of 1-thia-4,7-diazacyclononane ([9]aneN(2)S) and 1,4-dithia-7-azacyclononane ([9]aneNS(2)). X-Ray structural analyses, magnetic susceptibility, Mossbauer, EPR and electronic spectroscopy

The complexes [Fe([9]aneN(2)S)(2)][ClO4](2), [Fe([9]aneN(2)S)(2)][ClO4](3) and [Fe([9]aneNS(2))(2)][ClO4](2) ([9]aneN(2)S = 1-thia-4. 7-diazacyclononane and [9]aneNS(2) = 1,4-dithia-7-azacyclononane) have been prepared and the latter two characterised by X-ray crystallography. The Mossbauer spectra (isomer shift/mm s(-1), quadrupole splitting/mm s(-1), 4.2 K) for [Fe([9]aneN(2)S)(2)][ClO4](2) (0.52, 0.57), [Fe([9]aneN(2)S)(2)][ClO4](3) (0.25, 2.72) and [Fe([9]aneNS(2))(2)][ClO4](2) (0.43, 0.28) are typical for iron(II) and iron(III) complexes. Variable-temperature susceptibility measurements for [Fe([9]aneN(2)S)(2)][ClO4](2) (2-300 K) revealed temperature-dependent behaviour in both the solid state [2.95 mu(B) (300 K)-0.5 mu(B) (4.2 K)] and solution (Delta H degrees 20-22 kJ mol(-1), Delta S degrees 53-60 J mol(-1) K-1). For [Fe([9]aneN(2)S)(2)][ClO4](3) in the solid state [2.3 mu(B) (300 K)-1.9 mu(B) (4.2 K)] the magnetic data were fit to a simple model (H = -lambda L . S + mu L-z) to give the spin-orbit coupling constant (lambda) of -260 +/- 10 cm(-1). The solid-state X-band EPR spectrum of [Fe([9]aneN(2)S)(2)][ClO4](3) revealed axial symmetry (g(perpendicular to) = 2.607, g(parallel to) = 1.599). Resolution of g(perpendicular to) into two components at Q-band frequencies indicated a rhombic distortion. The low-temperature single-crystal absorption spectra of [Fe([9]aneN(2)S)(2)][ClO4](2) and [Fe([9]aneNS(2))(2)][ClO4](2) exhibited additional bands which resembled pseudotetragonal low-symmetry splitting of the parent octahedral (1)A(1g) --> T-1(2g) and (1)A(1g) ---> T-1(1g) transitions. However, the magnitude of these splittings was too large, requiring 10Dq for the thioether donors to be significantly larger than for the amine donors. Instead, these bands were tentatively assigned to weak, low-energy S --> Fe-II charge-transfer transitions. Above 200 K, thermal occupation of the high-spin T-5(2g) ground state resulted in observation of the T-5(2g) --> E-5(g) transition in the crystal spectrum of [Fe([9]aneN(2)S)(2)][ClO4](2). From a temperature-dependence study, the separation of the low-spin (1)A(1g) and high-spin T-5(2g) ground states was approximately 1700 cm(-1). The spectrum of the iron(III) complex [Fe([9]aneN(2)S)(2)][ClO4](3) is consistent with a low-spin d(5) configuration.

Flexible synthesis of enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro[4.5]decanes from propargylic and homopropargylic alcohols

A new approach to enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro [4.5] decanes is described and utilizes enantiomerically pure homopropargylic alcohols obtained from lithium acetylide opening of enantiomerically pure epoxides, which are, in turn, acquired by hydrolytic kinetic resolution of the corresponding racemic epoxides. Alkyne carboxylation and conversion to the Weinreb amide may be followed by triple-bond manipulation prior to reaction with a second alkynyllithium derived from a homo- or propargylic alcohol. In this way, the two ring components of the spiroacetal are individually constructed, with deprotection and cyclization affording the spiroacetal. The procedure is illustrated by acquisition of (2S,5R,7S) and (2R,5R,7S)-2-n-butyl-7-methyl-1,6-dioxaspiro[4.5]-decanes (1), (2S,6R,8S)-2-methyl-8-n-pentyl-1,7-dioxaspiro[5.5]undecane (2), and (2S,6R,8S)-2-methyl-8-n-propyl-1,7-dioxaspiro[5.5]undecane (3). The widely distributed insect component, (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (4), was acquired by linking two identical alkyne precursors via ethyl formate. In addition, [H-2(4)]-regioisomers, 10,10,11,11-[H-2(4)] and 4,4,5,5-[H-2(4)] of 3 and 4,4,5,5-[H-2(4)]-4, were acquired by triple-bond deuteration, using deuterium gas and Wilkinson's catalyst. This alkyne-based approach is, in principle, applicable to more complex spiroacetal systems not only by use of more elaborate alkynes but also by triple-bond functionalization during the general sequence.

Who fails to complete tuberculosis treatment? Temporal trends and risk factors for treatment interruption in a community-based directly observed therapy programme in a rural district of South Africa

SETTING: Hlabisa Tuberculosis Programme, Hlabisa, South Africa. OBJECTIVE: To determine trends in and risk factors for interruption of tuberculosis treatment. METHODS: Data were extracted from the control programme database starting in 1991. Temporal trends in treatment interruption are described; independent risk factors for treatment interruption were determined with a multiple logistic regression model, and Kaplan-Meier survival curves for treatment interruption were constructed for patients treated in 1994-1995. RESULTS: Overall 629 of 3610 surviving patients (17%) failed to complete treatment; this proportion increased from 11% (n = 79) in 1991/1992 to 22% (n = 201) in 1996. Independent risk factors for treatment interruption were diagnosis between 1994-1996 compared with 1991-1393 (odds ratio [OR] 1.9, 95% confidence interval [CT] 1.6-2.4); human immunodeficiency virus (HIV) positivity compared with HIV negativity (OR 1.8, 95% CI 1.4-2.4); supervised by village clinic compared with community health worker (OR 1.9, 95% CI 1.4-2.6); and male versus female sex (OR 1.3, 95% CI 1.1-1.6). Few patients interrupted treatment during the first 2 weeks, and the treatment interruption rate thereafter was constant at 1% per 14 days. CONCLUSIONS: Frequency of treatment interruption from this programme has increased recently. The strongest risk factor was year of diagnosis, perhaps reflecting the impact of an increased caseload on programme performance. Ensuring adherence to therapy in communities with a high level of migration remains a challenge even within community-based directly observed therapy programmes.

Evaluation of eight spring onion genotypes, sulphur nutrition and soil-type effects with an electronic nose

Genotype, sulphur (S) nutrition and soil-type effects on spring onion quality were assessed using a 32-conducting polymer sensor E-nose. Relative changes in sensor resistance ratio (% dR/R) varied among eight spring onion genotypes. The % dR/R was reduced by S application in four of the eight genotypes. For the other four genotypes, S application gave no change in % dR/R in three, and increased % dR/R in the other. E-nose classification of headspace volatiles by a two-dimensional principal component analysis (PCA) plot for spring onion genotypes differed for S fertilisation vs. no S fertilisation. Headspace volatiles data set clusters for cv. 'White Lisbon' grown on clay or on sandy loam overlapped when 2.9 [Mahalanobis distance value (D2) = 1.6], or 5.8-(D2 = 0.3) kg S ha-1 was added. In contrast, clear separation (D2 = 7.5) was recorded for headspace volatile clusters for 0 kg S hd-1 on clay vs. sandy loam. Addition of 5.8 kg S ha-1 increased pyruvic acid content (mmole g-1 fresh weight) by 1.7-fold on average across the eight genotypes. However, increased S from 2.9 to 5.8 kg ha-1 did not significantly (P > 0.05) influence % dR/R, % dry matter (DM) or total soluble solids (TSS) contents, but significantly (P < 0.05) increased pyruvic acid content. TSS was significantly (P < 0.05) reduced by S addition, while % DM was unaffected. In conclusion, the 32-conducting polymer E-nose discerned differences in spring onion quality that were attributable to genotype and to variations in growing conditions as shown by the significant (P < 0.05) interaction effects for % dR/R.

Isomers of 1,4,8,11-tetraazacyclotetradecane-6,13-dicarboxylate characterized as cobalt(III) complexes

The major trans (1) and minor cis (2) isomers of 1,4,8,11-tetraazacyclotetradecane-6,13-dicarboxylate have been characterized as the complexes [Co(1)](ClO4) and [Co(H-2)(OH2)]Cl(ClO4).H2O. The former crystallized in the C-2/c space group and the latter in the P2(1)/c space group, with cell parameters a 16.258(7), b 9.050(3), c 15.413(6) Angstrom, beta133.29(3)degrees, and a 9.694(4), b 16.135(1), c 12.973(5) Angstrom, beta 93.00(2)degrees, respectively. Their characterization completes identification of the respective trans and cis isomers for the series of C-pendant macrocycles also including 1,4,8,11-tetraazacyclotetradecane-6-amine-13-carboxylate ((3), (4)) and 1,4,8,11-tetraazacyclotetradecane-6,13-diamine ((5), (6)). The complexes show limited distortion from octahedral geometry with the strain in the presence of the coordinated C-pendant carboxylate significantly reduced compared with that for the C-pendant amine in analogues, a consequence mainly of six-membered as opposed to five-membered chelate rings involving the pendant donor. A comparison of the physical properties for the trans isomers of the octahedral complexes of (1), (3), and (5), which reflect progressively increasing strain, is presented.

Validity of (-)-[H-3]-CGP 12177A as a radioligand for the 'putative beta(4)-adrenoceptor' in rat atrium

1 We have recently suggested the existence in the heart of a 'putative beta(4)-adrenoceptor' based on the cardiostimulant effects of non-conventional partial agonists, compounds that cause cardiostimulant effects at greater concentrations than those required to block beta(1)- and Bz-adrenoceptors. We sought to obtain further evidence by establishing and validating a radioligand binding assay for this receptor with (-)-[H-3]-CGP 12177A ((-)-4-(3-tertiarybutylamino-2-hydroxypropoxy) benzimidazol-2-one) in rat atrium. We investigated (-)-[H-3]-CGP 12177A for this purpose for two reasons, because it is a nonconventional partial agonist and also because it is a hydrophilic radioligand. 2 Increasing concentrations of(-)-[H-3]-CGP 12177A, in the absence or presence of 20 mu M (-)-CGP 12177A to define non-specific binding, resulted in a biphasic saturation isotherm. Low concentrations bound to beta(1)- and beta(2)-adrenoceptors (pK(D) 9.4+/-0.1, B-max 26.9+/-3.1 fmol mg(-1) protein) and higher concentrations bound to the 'putative beta(4)-adrenoceptor' (pK(D) 7.5+/-0.1, B-max 47.7+/-4.9 fmol mg(-1) protein). In other experiments designed to exclude beta(1)- and beta(2)-adrenoceptors, (-)-[H-3]-CGP 12177A (1-200 nM) binding in the presence of 500 nM (-)-propranolol was also saturable (pK(D) 7.6+/-0.1, B-max 50.8+/-7.4 fmol mg(-1) protein). 3 The non-conventional partial agonists (-)-CGP 12177A (pK(i) 7.3+/-0.2), (+/-)-cyanopindolol (pK(i) 7.6+/-0.2), (-)-pindolol (pK(i) 6.6+/-0.1) and (+)-carazolol (pk(i), 7.2+/-0.2) and the antagonist (-)-bupranolol (pK(i) 6.6+/-0.2), all competed for (-)-[H-3]-CGP 12177A binding in the presence of 500 nM (-)-propranolol at the 'putative beta(4)-adrenoceptor', with affinities closely similar to potencies and affinities determined in organ bath studies. 4 The catecholamines competed with (-)-[H-3]-CGP 12177A at the 'putative beta(4)-adrenoceptor' in a stereoselective manner, (-)-noradrenaline (pK(iH) 6.3 +/- 0.3, pK(i), 3.5 +/- 0.1), (-)-adrenaline (pK(iH) 6.5 +/- 0.2, pK(iL) 2.9 +/- 0.1), (-)-isoprenaline (pK(iH) 6.2 +/- 0.5, pK(iL) 3.3 +/- 0.1), (+)-isoprenaline (pK(i) < 1.7), (-)-R0363 ((-)-(1-(3,4-dimethoxyphenethylamino)-3-(3,4-dihydroxyphenoxy)-2-propranol)oxalate, pK(i) 5.5 +/- 0.1). 5 The inclusion of guanosine 5-triphosphate (GTP 0.1 mM) had no effect on binding of (-)-CGP 12177A or (-)-isoprenaline to the 'putative beta(4)-adrenoceptor'. In competition binding studies, (-)-CGP 12177A competed with (-)-[H-3]-CGP 12177A for one receptor state in the absence (pK(i) 7.3 +/- 0.2) or presence of GTP (pK(i) 7.3 +/- 0.2). (-)-Isoprenaline competed with (-)-[H-3]-CGP 12177A for two states in the absence (pK(iH) 6.6 +/- 0.3, pK(iL) 3.5 +/- 0.1; % H 25 +/- 7) or presence of GTP (pK(iH) 6.2 +/- 0.5, pK(iL) 3.4 +/- 0.1; % H 37 +/- 6). In contrast, at beta(1)-adrenoceptors, GTP stabilized the low affinity state of the receptor for (-)-isoprenaline. 6 The specificity of binding to the 'putative beta(4)-adrenoceptor' was tested with compounds active at other receptors. High concentrations of the beta(4)-adrenoceptor agonists, BRL 37344 ((RR + SS)[4-[2-[[2-(3-chlorophenyl)-2-hydroxy -ethyl]amino]propyl]phenoxy]acetic acid, 6 mu M), SR 58611A (ethyl((7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphtyl-2-yloxy) acetate hydrochloride, 6 mu M), ZD 2079 ((+/-)-1-phenyl-2-(2-4-carboxymethylphenoxy)-ethylamino)ethan-1-ol, 60 mu M), CL 316243 (disodium (R,R)-5-[2-[2-(3-chlorophenyl)-2-hydroxyethyl-amino]propyl]- 1,3-benzodioxole-2,2-dicarboxylate, 60 mu M) and antagonist SR 59230A (3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-2S-2-propanol oxalate, 6 mu M) caused less than 22% inhibition of (-)-[H-3]-CGP 12177A binding in the presence of 500 nM (-)-propranolol. Histamine (1 mM), atropine (1 mu M), phentolamine (10 mu M), 5-HT(100 mu M) and the 5-HT4 receptor antagonist SE 207710 ((1-butyl-4-piperidinyl)-methyl 8-amino-7-iodo-1 ,4-benzodioxan-5-carboxylate, 10 nM) caused less than 26% inhibition of binding. 7 Non-conventional partial agonists, the antagonist (-)-bupranolol and catecholamines all competed for (-)-[H-3]-CGP 12177A binding in the absence of (-)-propranolol at beta(1)-adrenoceptors, with affinities (pK(i)) ranging from 1.6-3.6 log orders greater than at the 'putative beta(4)-adrenoceptor'. 8 We have established and validated a radioligand binding assay in rat atrium for the 'putative beta(4)-adrenoceptor' which is distinct from beta(1)-, beta(2)- and beta(3)-adrenoceptors. The stereoselective interaction with the catecholamines provides further support for the classification of the receptor as 'putative beta(4)-adrenoceptor'.

Macrocycle formation through carbon acid-formaldehyde condensation reactions of bis(propane-1,2-diamine)- and bis (2-methylpropane-1,2-diamine)-copper(II) ions

The reaction of the bis(1,2-diamine) copper(II) complexes of racemic propane-1,2-diamine (pn) and 2-methylpropane-1,2-diamine (dmen) with formaldehyde and nitroethane in methanol under basic conditions yields minor macrocyclic condensation products in addition to the major acyclic products. Where C-pendant methyl groups on the pair of coordinated diamines are in cis dispositions, the first -NH-CH2-C(CH3)(NO2)-CH2-NH- ring formation occurs at amine pairs distant from these C-methyl substituents, and further reaction to yield a macrocycle is not observed. However, where the C-methyl substituents are in trans dispositions, the chemistry proceeds to yield the macrocycle. Commencing with pn, trans-(6,13-diammonio-2,6,9,13-tetramethyl-1,4,7,10-tetraazacyclotetradecane)copper(II) perchlorate formed and crystallized in the space group P2(1)/n, with a 9.782(2), b 9.2794(6), c 17.017(4) Angstrom, beta 103.24(1)degrees. The copper ion is found in a square-planar environment, with the two methyl groups of the pn residues and the pairs of introduced pendant groups all in trans arrangements.

Rearrangement of diflunisal acyl glucuronide into its beta-glucuronidase-resistant isomers facilitates transport through the small intestine to the colon of the rat

Many non-steroidal anti-inflammatory drugs (NSAIDs) which form acyl glucuronide conjugates as major metabolites have shown an antiproliferative effect on colorectal tumors. This study assesses the extent to which rearrangement of an acyl glucuronide metabolite of a model NSAID into beta -glucuronidase-resistant isomers facilitates its passage through the small intestine to reach the colon. Rats were dosed orally with diflunisal (DF), its acyl glucuronide (DAG) and a mixture of rearrangement isomers (iso-DAG) at 10 mg DF equivalents/kg. The parent drug DF appeared in plasma after all doses, with maximum concentrations of 20.5 +/- 2.5, 28.8 +/- 8.3 and 11.0 +/- 1.6 mug DF/ml respectively, obtained at 3.8 +/- 0.3, 3.6 +/- 1.8 and 7.5 +/- 0.9 hr after the DF, DAG and iso-DAG doses respectively. At 48 hr, 16.2 +/- 3.3, 19.8 +/- 0.8 and 42.9 +/- 10.1% of the doses respectively were recovered in feces, with less than or equal to 1% remaining in the intestine. About half of each dose was recovered as DF and metabolites in 48 hr urine: for DF and DAG doses, the majority was in the first 24 hr urine. whereas for iso-DAG doses, recoveries in the first and second 24 hr periods were similar. The results show that hydrolysis of both DAG and iso-DAG, and absorption of liberated DF, occur during passage through the gut, but that these processes occur more slowly and to a lesser degree for iso-DAG. The intrinsic hydrolytic capacities of various intestinal segments (including contents) towards DAG and iso-DAG were obtained by incubating homogenates under saturating concentrations of DAG/iso-DAG at 37 degreesC. Upper small intestine, lower small intestine, caecum and colon released 2400, 3200, 9200 and 22800 mug DF/hr/g tissue plus contents respectively from DAG substrate, and 18, 10, 140 and 120 mug DF/hr/g tissue plus contents respectively from iso-DAG substrate. The much greater resistance of iso-DAG to hydrolysis appears attributable to its resistance to beta -glucuronidases. The data suggest that in rats dosed with DF, DAG excreted in bile would be substantially hydrolysed in the small intestine and liberated DF reabsorbed, but that portion which rearranges to iso-DAG would likely reach the colon. (C) 2001 Elsevier Science Inc. All rights reserved.

Energy profiles for ketene cyclizations. interconversion of 1,3-oxazin-6-ones, mesoionic 1,3-oxazinium olates and acylketenes, imidoylketenes, oxoketenimines, and cyclization products

The energy surface connecting oxazinium olates 9, several possible conformers of ketenes 10 and 11, and the final cyclization products 12, 13 and 14, as well as the isomeric 1,3-oxazine-6-ones 15, ring opening of the latter to N-acylimidoylketenes 16, and subsequent rearrangement of 16 to oxoketenimines 17, azetinones 18, and the cyclization products 19 and 20 are evaluated computationally at the B3LYP/6-31G* and B3LYP/6-311+G*//B3LYP/6-31G* levels. The cyclizations of ketenes to oxazinium olates 9 and oxazines 15 have the characteristics of pseudopericyclic reactions. Plots of the energy vs internal reaction coordinate for the cyclization of transoid acylketenes such as 10 to 9 (via TS1) and 16 to 15 (via TS7) feature two inflection points and indicate that the part of the energy surface above the lower inflection points describe internal rotation of the acyl function in the ketene moiety, and the part below this point describes the cyclization of the cisoid ketene to the planar mesoionic oxazinium olate 9 or oxazinone 15. The 1,3-shifts of the OR group that interconvert ketenes 16 and ketenimines 17 via four-membered cyclic transition states TS8 behave similarly, the first portion (from the ketenimine side) of the activation barrier being due largely to internal rotation of substituents, and the top part being due to the 1,3-shift proper.

Outcome with calcium channel antagonists after myocardial infarction: A community-based study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared,vith patients taking neither calcium antagonists nor beta-blockers. Conclusions. These results are consistent with randomized trial data showing benefit from beta blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists. (C) 1998 by the American College of Cardiology.

Lemon oil to beta-cyclodextrin ratio effect on the inclusion efficiency of beta-cyclodextrin and the retention of oil volatiles in the complex

Microencapsulation of lemon oil was undertaken with beta-cyclodextrin using a precipitation method at the five lemon oil to beta-cyclodextrin ratios of 3:97, 6:94, 9:91, 12:88, and 15:85 (w/w) in order to determine the effect of the ratio of lemon oil to beta-cyclodextrin on the inclusion efficiency of beta-cyclodextrin for encapsulating oil volatiles. The retention of lemon oil volatiles reached a maximum at the lemon oil to beta-cyclodextrin ratio of 6:94; however, the maximum inclusion capacity of beta-cyclodextrin and a maximum powder recovery were achieved at the ratio of 12:88, in which the beta-cyclodextrin complex contained 9.68% (w/w) lemon oil. The profile and proportion of selected flavor compounds in the beta-cyclodextrin complex and the starting lemon oil were not significantly different.

N-methylation of diamino-substituted macrocyclic complexes: Intermolecular reactions

Two N-based isomeric copper(II) complexes of the macrocycle trans-6,13-dimethyl-6,13-bis(dimethylamino)1,4,8,11-tetraazacyclotetradecane (L(3)) have been synthesized and characterised spectroscopically and structurally: alpha-[CuL(3)(OH2)(2)]Cl-2, monoclinic, space group C2/m, a = 12.908(4), b = 12.433(2), c = 7.330(2) Angstrom, beta = 105.87(2)degrees, Z = 2; beta-[CuL(3)(OClO3)(2)]. 2H(2)O, monoclinic, space group P2(1)/c, a = 9.708(3), b = 9.686(3), c = 14.202(4) Angstrom, beta = 106.17(1)degrees, Z = 2. The two isomers exhibit very similar co-ordination spheres but significantly different visible electronic maxima. This difference is attributed to an intramolecular N ... H contact between the pendant dimethylamino group and an adjacent secondary amine H atom.

N-methylation of diamino-substituted macrocyclic complexes: Intramolecular cyclisation

Two new macropolycyclic hexaamines L(2) and L(4) as their copper(II) complexes have been isolated as products from the condensation of the diamino-substituted macrocyclic complex trans-(6,13-dimethyl-1,4,8,11-tetraazacyclo-tetradecane-6,13-diamine)copper(II) [CuL(1)](2+) with aqueous formaldehyde. Both of the complexes exhibit methylene bridges between the pendant amine and the adjacent co-ordinated macrocyclic N-donors. Their crystal structures have been determined: [CuL(2)(NCS)][SCN], triclinic, space group P (1) over bar, a = 7.133(2), b = 9.813(2), c = 16.745(3) Angstrom, alpha = 101.05(2), beta = 99.36(2), gamma = 99.77(2)degrees, Z = 2; [CuL(4)Cl][ClO4]. H2O, triclinic, space group P (1) over bar, a = 9.3327(8), b = 10.8989(6), c = 12.672(1) Angstrom, alpha = 68.591(6), beta = 78.899(6), gamma = 87.384(6)degrees, Z = 2. The complexes exhibit square-pyramidal geometries, and significantly lower-energy electronic maxima relative to their parent complex [CuL(1)](2+). Electrochemistry of [CuL(2)](2+) revealed a reversible Cu-II-Cu-I redox couple, by contrast to those of macromonocyclic analogues.

Diverse solid-state and solution structures within a series of hexaamine dicopper(II) complexes

Mono- and dicopper(II) complexes of a series of potentially bridging hexaamine ligands have been prepared and characterized in the solid state by X-ray crystallography. The crystal structures of the following Cu-II complexes are reported: [Cu(HL3)](ClO4)(3), C11H31Cl3CuN6O12, monoclinic, P2(1)/n, a = 8.294(2) Angstrom, b = 18.364(3) Angstrom, c = 15.674(3) Angstrom, beta = 94.73(2)degrees, Z = 4; {[Cu-2(L-4)(CO3)](2)}(ClO4)(4). 4H(2)O, C40H100Cl4Cu4N12O26, triclinic, P (1) over bar, a = 9.4888(8) Angstrom, b=13.353(1) Angstrom,. c = 15.329(1) Angstrom, alpha = 111.250(7)degrees, beta = 90.068(8)degrees, gamma = 105.081(8)degrees, Z=1; [Cu-2(L-5)(OH2)(2)](ClO4)(4), C(13)H(36)Cl(4)Cu(2)Z(6)O(18), monoclinic, P2(1)/c, a = 7.225(2) Angstrom. b = 8.5555(5) Angstrom, c = 23.134(8) Angstrom, beta = 92.37(1)degrees, Z = 2; [Cu-2(L-6)(OH2)(2)](ClO4)(4). 3H(2)O, C14H44Cl4Cu2N6O21, monoclinic, P2(1)/a, a = 15.204(5) Angstrom, b = 7.6810(7) Angstrom, c = 29.370(1) Angstrom, beta = 100.42(2)degrees, Z = 4. Solution spectroscopic properties of the bimetallic complexes indicate that significant conformational changes occur upon dissolution, and this has been probed with EPR spectroscopy and molecular mechanics calculations.

Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-l/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines. (C) 2002 Lippincott Williams Wilkins.