Fluoroquinolone use for uncomplicated urinary tract infections in women: a retrospective cohort study.

OBJECTIVES: The United States Food & Drug Administration released an advisory in 2016 that fluoroquinolones be relegated to second-line agents for uncomplicated urinary tract infections (UTIs) given reports of rare but serious side effects; similar warnings have followed from Health Canada and the European Medicines Agency. The objective was to determine whether alternative non-fluoroquinolone agents are as effective as fluoroquinolones in the treatment of UTIs. METHODS: We conducted a retrospective population-based cohort study using administrative health data from six Canadian provinces. We identified women (n = 1 585 997) receiving antibiotic treatment for episodes of uncomplicated UTIs (n = 2 857 243) between January 1 2005 and December 31 2015. Clinical outcomes within 30 days from the initial antibiotic dispensation were compared among patients treated with a fluoroquinolone versus non-fluoroquinolone agents. High-dimensional propensity score adjustments were used to ensure comparable treatment groups and to minimize residual confounding. RESULTS: Fluoroquinolone use for UTI declined over the study period in five of six Canadian provinces and accounted for 22.3-48.5% of treatments overall. The pooled effect across the provinces indicated that fluoroquinolones were associated with fewer return outpatient visits (OR 0.89, 95%CI 0.87-0.92), emergency department visits (OR 0.74, 95%CI 0.61-0.89), hospitalizations (OR 0.83, 95%CI 0.77-0.88), and repeat antibiotic dispensations (OR 0.77, 95%CI 0.75-0.80) within 30 days. CONCLUSIONS: Fluoroquinolones are associated with improved clinical outcomes among women with uncomplicated UTIs. This benefit must be weighed against the risk of fluoroquinolone resistance and rare but serious fluoroquinolone side effects when selecting first-line treatment for these patients.

Enantiopure Phospha[1]ferrocenophanes: Textbook Examples of Through-Space Nuclear Spin-Spin Coupling.

Three enantiopure phospha[1]ferrocenophanes (2R ) equipped with either a phenyl, an isopropyl, or a tert-butyl group at the bridging phosphorus atom were synthesized by a salt-metathesis approach in isolated yields between 52 and 63 %. The chirality in these strained sandwich compounds stems from the planar-chiral ferrocene moiety, which is symmetrically equipped with two iPr groups adjacent to phosphorus. Surprisingly, all three phospha[1]ferrocenophanes show an uncommon through-space nuclear 1 H-31 P coupling. As a result of the embedded symmetry, these new compounds are ideal examples to differentiate between through-space and through-bond coupling mechanisms in NMR spectroscopy.

Substrate-Controlled Diastereoselectivity Reversal in NHC-Catalyzed Cross-Benzoin Reactions Using N-Boc-N-Bn-Protected α-Amino Aldehydes.

The effectiveness of utilizing N-Bn-N-Boc-α-amino aldehydes in cross-benzoin reactions with heteroaromatic aldehydes is demonstrated. The reaction is both chemoselective and syn-selective, making it complementary to the anti-selective cross-benzoin reaction of NHBoc-α-amino aldehydes. Good diastereoselectivity is obtained for a variety of amino aldehydes, including nonhindered ones. A Felkin-Anh model can be used to rationalize the observed diastereoselectivity.

Chiral bora[1]ferrocenophanes: syntheses, mechanistic insights, and ring-opening polymerizations.

A series of new boron-bridged [1]ferrocenophanes ([1]FCPs) was prepared by salt-metathesis reactions between enantiomerically pure dilithioferrocenes and amino(dichloro)boranes (Et2 NBCl2 , iPr2 NBCl2 , or tBu(Me3 Si)NBCl2 ). The dilithioferrocenes were prepared in situ by lithium-bromine exchange from the respective planar-chiral dibromides (Sp ,Sp )-[1-Br-2-(HR2 C)H3 C5 ]2 Fe (R=Me or Et). In most of the cases, mixtures of the targeted [1]FCPs 4 and the unwanted 1,1'-bis(boryl)ferrocenes 5 were formed. The product ratio depends on the bulkiness of the amino group, the speed of addition of the amino(dichloro)borane, the alkyl group on Cp rings, and in particular on the reaction temperature. The formation of strained [1]FCPs is strongly favored by increased reaction temperatures. Secondly, CHEt2 groups at Cp rings favored the formation of the targeted [1]FCPs stronger than CHMe2 groups. These discoveries open up new possibilities to further suppress the formation of unwanted byproducts by a careful choice of the reaction temperature and through tailoring the bulkiness of CHR2 groups on ferrocene. Thermal ring-opening polymerizations of selected boron-bridged [1]FCPs gave metallopolymers with a Mw of 10 kDa (GPC).

Tautomerism and metal complexation of 2-acylmethyl-2-oxazolines: a combined synthetic, spectroscopic, crystallographic and theoretical treatment.

A synthetic, structural and theoretical investigation into the solid-state, solution and gas phase structure(s) of six 2-acylmethyl-4,4-dimethyl-2-oxazolines is reported. Four of these materials, viz.α-[(4,5-dihydro-4,4-dimethyl-2-oxazolyl)methylene]benzenemethanol (3a), α-[(4,5-dihydro-4,4-dimethyl-2-oxazolyl)methylene]-(4-nitrobenzene)methanol (3b), 1-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-3,3-dimethyl-1-buten-2-ol (3d) and (E)-1-phenyl-2-((3aR)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-ylidene)ethanone (3f) have been characterised in the solid-state by single crystal X-ray diffraction studies. These data represent the first solid-state structural studies of this class of compounds and details the first synthesis and full characterisation of chiral derivative 3f. All four of these materials are shown to exist in the solid phase in the enamine tautomeric form (e.g., 3a is best described as 2-[4,4-dimethyl-2-oxazolidinylidene]-1-phenylethanone) and it is suggested (NMR, IR) that this isomeric form is likely also retained in solution (e.g., CDCl3) as the more stable isomer. An investigation of the relative gas phase stabilities of the three possible (i.e., the (Z)-enol, keto and enamine) isomers of all five compounds by DFT at the B3LYP/6-311G(d) level of theory confirms the latter as the most stable form. The energy differences between the enamine and keto tautomers have been calculated to be the lowest for derivative 3d. These results are compared and contrasted with the previously reported NMR studies of such compounds which have identified the keto form as being a minor (albeit solution) tautomer. Equilibrium solution tautomer distributions for 3d are found to be solvent dependent. The protonated form of 3a, isolated as the HSO4(-) salt (i.e.4a), has been further characterised in the solid state by single crystal X-ray diffraction. These data represent the first example of a protonated oxazoline to be structurally elucidated and confirms that upon protonation, the keto (oxazoline) tautomer is the energetically favoured form in the solid-state. This observation is further supported by DFT studies for the gas phase protonated forms of such materials. Further DFT (B3LYP/6-311G(d)) calculations employing the SM8 or SMD solvation models were then applied to address the observed solution isomeric distribution for 3d; these results corroborate the gas phase theoretical treatment and also yield values that predict the higher solution stability of the enamine form as observed, although they fail to account for the existence of the keto form as a minor solution state tautomer. To access the availability of an enol-form, via hypothetical de-protonation to the enolate, compound 3a was treated with hydrated Cu(NO3)2 in EtOH solution. The resulting isolated green-coloured product (5), the first metal derivative of this entire class of ligands, is best described (IR, X-ray diffraction) as a coordinated enolate complex, i.e., Cu(3a-H)2. Complex 5 crystallizes in the P21/c space group with four molecules in the unit cell. The coordination geometry around the formal Cu(2+) metal centre is determined to be highly distorted square planar in nature (τ4 = 0.442). TD-DFT is used to give a reasonable explanation for the intensity of the absorbance band observed in the visible region for solutions of 5. These latter experiments strongly suggest that the title class of compounds may have considerable potential as ligands in coordination chemistry and/or metal-mediated catalysis.

Bis-diimidazolylidine complexes of nickel: investigations into nickel catalyzed coupling reactions.

Air and moisture stable homoleptic bis(diimidazolylidine)nickel(II) complexes, ([(diNHC)(2)Ni](2+)) 3a,b and their corresponding silver(I) 4a,b and palladium(II) 5a,b complexes were synthesized and characterized by NMR and single crystal X-ray analysis. The catalytic potential of complex 3a was assessed in Mizoroki-Heck and Suzuki-Miyaura coupling reactions. In the Suzuki-Miyaura coupling reaction, nickel precatalyst 3a was active for the coupling of aryl chlorides as well as aryl fluorides. The analogously synthesized Pd(II) complexes resulted in formation of (diNHC)PdCl(2) species which were not active for the coupling of aryl fluorides. For the Mizoroki-Heck reaction, it was found that aryl iodides could be activated in the absence of nickel or palladium precatalysts when using Na(2)CO(3) or NEt(3) as base while aryl iodides and aryl bromides could be activated in the Suzuki-Miyaura reaction sans precatalyst when K(3)PO(4) was used as base.

Unusual cationic trinuclear nickel clusters incorporating oxazolines or N,N,N',N'-tetramethylethylene-1,2-diamine: applications in olefin polymerization.

The synthesis and characterization of two rare examples of the nickel(II)-containing trinuclear clusters of the general formula µ(3)-halido-µ(3)-hydroxotris(µ-halido)tris(L) trinickel(II) halide [halide = Cl (2), Br (3); L = 4,4-dimethyl-2-(o-anilinyl)-2-oxazoline] are described. These materials are compared and contrasted to the "parent" chloride salt (1) of this series (L = N,N,N',N'-tetramethylethylene-1,2-diamine and halide = Cl) and its congeners; 2 and 3 represent the first oxazoline-containing clusters of this structural class. Both 1 and 2 are shown to be active catalysts for the polymerization of olefins (styrene, methyl methacrylate, etc.) using a stoichiometric equivalent of methylaluminoxane as the copromoter, a situation that gives good yields of syndiotactic rich polymers. Density functional theory (B3LYP/6-31G*/LANL2DZ) is employed to hypothesize the likely origin of the activity demonstrated by these compounds.

Performance of comorbidity measures for predicting outcomes in population-based osteoporosis cohorts.

UNLABELLED: The performance of five comorbidity measures, including the Charlson and Elixhauser indices, was investigated for predicting mortality, hospitalization, and fracture outcomes in two osteoporosis cohorts defined from administrative databases. The optimal comorbidity measure depended on the outcome of interest, although overall the Elixhauser index performed well. INTRODUCTION: Studies that use administrative data to investigate population-based health outcomes often adopt risk-adjustment models that include comorbidities, conditions that coexist with the index disease. There has been limited research about the measurement of comorbidity in osteoporotic populations. The study purpose was to compare the performance of comorbidity measures for predicting mortality, fracture, and health service utilization outcomes in two cohorts with diagnosed or treated osteoporosis. METHODS: Administrative data were from the province of Saskatchewan, Canada. Osteoporosis cohorts were identified from diagnoses in hospital and physician data and prescriptions for osteo-protective medications using case definitions with high sensitivity or high specificity. Five diagnosis- and medication-based comorbidity measures and five 1-year outcomes, including mortality, hospitalization (two measures), osteoporotic-related fracture, and hip fracture, were defined. Performance of the comorbidity measures was assessed using the c-statistic (discrimination) and Brier score (prediction error) for multiple logistic regression models. RESULTS: In the specific cohort (n = 9,849) for the mortality outcome, the Elixhauser index resulted in the largest improvement (8.96%) in the c-statistic and lowest Brier score compared to a model that contained demographic and socioeconomic variables, followed by the Charlson index (6.06%). For hospitalization, the number of different diagnoses resulted in the largest improvement (14.01%) in the c-statistic. The Elixhauser index resulted in significant improvements in the c-statistic for osteoporosis-related and hip fractures. Similar results were observed for the sensitive cohort (n = 28,068). CONCLUSIONS: Recommendations about the optimal comorbidity measure will vary with the outcome under investigation. Overall, the Elixhauser index performed well.

Oxazoles revisited: On the nature of binding of benzoxazole and 2-methylbenzoxazole with the zinc and palladium halides.

A synthetic and structural (X-ray) investigation into the bonding modes of benzoxazole (box) and 2-methylbenzoxazole (Mebox) ligands with halide precursors of Zn and Pd has been undertaken to clarify earlier discrepancies concerning the nature of the bonding mode(s) of the two azoles. In four structurally characterised examples, all contain the title ligands in a κ(1)N bonding motif. Calculations at the density functional level (DFT) of theory (B3LYP) confirm the ground state stability of this class of coordination for several hypothetical Pd and Zn (gas phase) compounds. The attempt to obtain suitable crystalline material of PdCl(2)(box)(2) (i.e., 5) leads to substantial complex degradation. One minor product of this process has been identified (X-ray) as the diarylformamidinato complex C(26)H(22)N(4)O(4)Pd, presumably formed via a complex combination of the decomposition products of both free box and 5.

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones.

This study demonstrated that replacement of the axial protons on the C2 and C6 atoms of various 1-methyl-3,5-bis(benzylidene)-4-piperidones 3 by a dimethylene bridge leading to series 2 lowered cytotoxic potencies. Four compounds 2a and 3a-c emerged as lead molecules based on their toxicity towards different neoplasms and their selective toxicity for malignant rather than normal cells. Some possible reasons for the disparity between the IC(50) values in the two series of compounds are presented based on molecular modeling, logP values and respiration in rat liver mitochondria.

Cyclo-linopeptide A methanol solvate.

Crystals of the title compound, C(57)H(85)N(9)O(9)·CH(4)O, the methanol solvate of a nine peptide polypeptide, cyclo-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val), were obtained after separation of the cyclic peptide from flax oil. The cyclo-linopeptide A (CLP-A) mol-ecules are linked in chains along the a axis by N-H⋯O hydrogen bonds. Each methanol O atom is hydrogen bonded to one O atom and two N-H groups in the same CLP-A mol-ecule. There are a total of eight hydrogen bonds in each CLP-A-MeOH unit.

Synthesis of palladacycles employing iminoisoindolines as monoanionic bidentate ligands.

A series of air- and moisture-stable iminoisoindoline-based palladacycles have been prepared in two operationally simple steps from commercially available reagents. para-Substituted N,N'-diphenyliminoisoindoline ligands are easily synthesized from phthalaldehyde and para-substituted anilines and further reaction of the iminoisoindoline ligands with Pd(OAc)(2) in dichloromethane at room temperature results in formation of six-membered [C,N] dinuclear cyclopalladated complexes with the general formula [(iminoisoindoline)Pd(micro-OAc)](2). The resulting palladacyclic complexes were tested as precatalysts in Heck and Suzuki coupling reactions.

Synthesis and characterization of aluminum- and gallium-bridged [1.1]chromarenophanes and [1.1]molybdarenophanes.

The synthesis and structural characterization of the first [1.1]chromarenophanes and the first [1.1]molybdarenophanes are described. A salt-metathesis reaction of [2-(Me 2NCH 2)C 6H 4]AlCl 2 with freshly prepared [Cr(LiC 6H 5) 2].TMEDA (TMEDA = N, N, N', N'-tetramethylethylenediamine) resulted in the dialumina[1.1]chromarenophane [{2-(Me 2NCH 2)C 6H 4}Al(eta (6)-C 6H 5) 2Cr] 2 ( 2a). The poor solubility of 2a in organic solvents prompted us to synthesize the new intramolecularly coordinated aluminum- and gallium dichlorides [5- tBu-2-(Me 2NCH 2)C 6H 3]ECl 2 [E = Al ( 3a), Ga ( 3b)] in which the phenyl group was equipped with a tert-butyl group. Salt-metathesis reactions of 3a and 3b, respectively, with freshly prepared [M(LiC 6H 5) 2].TMEDA (M = Cr, Mo) resulted in four new [1.1]metallarenophanes of the general type [{5- tBu-2-(Me 2NCH 2)C 6H 3}E(eta (6)-C 6H 5) 2M] 2 [E = Al, M = Cr ( 4a); E = Ga, M = Cr ( 4b); E = Al, M = Mo ( 5a); E = Ga, M = Mo ( 5b)]. 2a, 4a, b, and 5a, b have been structurally characterized by single-crystal analysis [ 2a.1/2C 6H 12: C 48H 56Al 2Cr 2N 2, monoclinic, P2 1/ c, a = 9.9117(9) A, b = 19.9361(16) A, c = 10.638(2) A, alpha = 90 degrees , beta = 112.322(5) degrees , gamma = 90 degrees , Z = 2; 4a.2C 6H 6: C 62H 72Al 2Cr 2N 2, monoclinic, P2 1/ c, a = 10.9626(9) A, b = 19.3350(18) A, c = 12.4626(9) A, alpha = 90 degrees , beta = 100.756(5) degrees , gamma = 90 degrees , Z = 2; 4b.2C 6H 6: C 62H 72Cr 2Ga 2N 2, monoclinic, P2 1/ c, a = 10.8428(2) A, b = 19.4844(4) A, c = 12.4958(2) A, alpha = 90 degrees , beta = 100.6187 degrees , gamma = 90 degrees , Z = 2; 5a.2C 6H 6: C 62H 72Al 2Mo 2N 2, triclinic, P1, a = 10.4377(4) A, b = 11.6510(4) A, c = 11.6514(4) A, alpha = 73.545(3) degrees , beta = 89.318(2) degrees , gamma = 76.120(2) degrees , Z = 1; 5b.2C 6H 6: C 62H 72Ga 2Mo 2N 2, triclinic, P1, a = 10.3451(5) A, b = 11.6752(6) A, c = 11.6900(5) A, alpha = 73.917(3) degrees , beta = 89.550(3) degrees , gamma = 76.774(2) degrees , Z = 1]. All five [1.1]metallarenophanes 2a, 4a, b, and 5a, b crystallize as anti isomers with both Me 2N donor groups in exo positions ( C i point group symmetry). The new [1.1]metallarenophanes show NMR spectra that can be interpreted as being caused by time-averaged C 2 h symmetrical species, which is consistent with the findings of their molecular structures in the solid state. Variable-temperature (1)H NMR measurements for 4a, b and 5a, b (500 MHz; -90 to 90 degrees C) revealed only peak broadening in the lower temperature range of -70 to -90 degrees C. (1)H NMR saturation transfer difference experiments did not show an expected anti-to-anti isomerization, rendering the new [1.1]metallacyclophanes rigid on the NMR time scale. Electrochemical measurements were performed for 4a, b and 5a, b. However, reproducible cyclic voltammograms could only be obtained for the two gallium species 4b and 5b, revealing the expected weak communication between the two transition-metal atoms in both compounds (class II).

N-(2,6-Diisopropyl-phen-yl)formamide.

The title compound, C(13)H(19)NO, exhibits a non-planar structure in which the 2,6-diisopropyl-phenyl ring is tilted at a dihedral angle of 77.4 (1)° with respect to the formamide group. This is the largest dihedral angle known among structurally characterized formamides. The mol-ecules are linked via N-H⋯O hydrogen bonds, forming infinite chains which run along the b-axis directions.

The galla[1]ferrocenophane {[dimeth-yl(2-pyrid-yl)sil-yl]bis-(trimethyl-silyl)methyl-κC,N}(ferrocene-1,1'-di-yl)gallium(III).

The title compound, [GaFe(C(5)H(4))(2)(C(14)H(28)NSi(3))] or [{(2-H(4)C(5)N)Me(2)Si}(Me(3)Si)(2)C]Ga(C(5)H(4))(2)Fe, a galla[1]ferrocenophane, crystallizes with two independent mol-ecules in the asymmetric unit. In these strained sandwich compounds, the angles between the planes of the two π-ligands are 15.4 (2) and 16.4 (2)°, with gallium in a distorted tetrahedral coordination environment.

Bis[2-phenyl-1-(phenyl-iminio)isoindo-line] di-µ-chlorido-bis-[dichloridopalladate(II)] benzene disolvate.

In the title compound, (C(20)H(17)N(2))(2)[Pd(2)Cl(6)]·2C(6)H(6), the dichloride-bridged [Pd(2)Cl(6)](2-) anion lies across an inversion center with each Pd(II) ion in a slightly distorted square-planar environment. In the crystal structure, two cations and an anion are connected via N-H⋯Cl hydrogen bonds between the NH groups of the iminioisoindoline cations and terminal Cl atoms of a hexa-chloridodipalladate(II) anion. The Pd-Cl distance of the terminal chloride engaged in hydrogen bonding is slightly longer than the Pd-Cl distance of the adjacent terminal chloride which is not involved in hydrogen bonding.

Cytotoxic 3,5-bis(benzylidene)piperidin-4-ones and N-acyl analogs displaying selective toxicity for malignant cells.

A series of 3,5-bis(benzylidene)piperidin-4-ones 1, 1-acryloyl-3,5-bis(benzylidene)piperidin-4-ones 2 and adducts of 2 with sodium 2-mercaptoethanesulfonate (mesna), namely series 3, were prepared as candidate cytotoxic agents. These compounds were examined against neoplastic HSC-2, HSC-4 and HL-60 cells as well as HGF, HPC and HPLF normal cell lines and many of the compounds displayed selective toxicity for malignant cells. The CC50 values of the analogs in series 2 towards the cancer cell lines were mainly submicromolar. The relative potencies, selectivity and logP values were in the order of 2>1>3. The sulfonic acid group of a representative compound in series 3 was replaced by a thiol function to produce 4 leading to substantial increases in cytotoxic potencies and hydrophobicity indicating that the presence of a hydrophilic sulfonic acid group was disadvantageous in terms of potency. Molecular modeling suggested that the superior cytotoxicity of various members of series 1-3 over an acyclic analog 5 may have been due to the greater torsion angles theta1 and theta2 created between the arylidene aryl rings and the adjacent olefinic groups in series 1-3.

Host factors, occupation, and testicular cancer in Saskatchewan, Canada: 1979-2002.

The incidence rates of testicular cancer are increasing in several countries, especially among younger adults. The role of agricultural exposure in the etiology of testicular cancer is contentious. We extracted information related to the host, lifestyle, and tumor characteristics from the files of the Saskatchewan Cancer Agency for all cases (n = 517) of testicular cancer diagnosed in Saskatchewan between 1979 and 2000. The following questions were the subject of this initial inquiry: (1) Are tumor characteristics similar or different among occupational groups dichotomized into farmer/nonfarmer? (2) Are host characteristics similar or different among occupational groups? (3) Is farming as an occupation one of the independent predictors of tumor stage at diagnosis? Statistical analyses were restricted on 486 cases. The nonfarmers (n = 349) had smaller tumors in length on average, and more of them were diagnosed at stage I compared to farmers (n = 72). Occupation was not recorded for 65 cases. Farmers were older than nonfarmers. In logistic regression analyses with adjustment for relevant variables as cited in the literature, individuals with nonseminomas [OR (95% CI) 1.99 (1.30-3.31)] and < or = 26 years old at diagnosis [2.12 (1.15-3.93)] were significantly more likely to be diagnosed with a stage 2 or higher tumor. Farmers were significantly more likely than nonfarmers to be diagnosed at stage 2 or higher [1.76 (1.00-3.10)]. Based on our data, the significant predictors of being diagnosed with stage 2 and higher are: presence of nonseminoma, < or = 26 years old, and farming as an occupation.

[1]molybdarenophanes: strained metallarenophanes with aluminum, gallium, and silicon in bridging positions.

The first [1]molybdarenophanes were synthesized and structurally characterized. The aluminum and gallium compounds [(Me2Ntsi)Al(eta6-C6H5)2Mo] (2a) and [(Me2Ntsi)Ga(eta6-C6H5)2Mo] (2b) [Me2Ntsi = C(SiMe3)2(SiMe2NMe2)] were obtained from [Mo(LiC6H5)2].TMEDA and (Me2Ntsi)ECl2 [E = Al, Ga] in analytical pure form with isolated yields of 74% (2a) and 52% (2b). The silicon-bridged species [Ph2Si(eta6-C6H5)2Mo] (2c) was synthesized from [Mo(LiC6H5)2].TMEDA and Ph2SiCl2. Compound 2c was isolated as a crystalline material in an approximately 90% overall purity, from which a single crystal was used for X-ray analysis. The molecular structures of all three [1]molybdarenophanes 2a-c were determined by single-crystal X-ray analysis. The ring-tilt angle alpha was found to be 18.28(17), 21.24(10), and 20.23(29) degrees for 2a, 2b, and 2c, respectively. Variable temperature NMR measurements of 2a and 2b (-80 to 80 degrees C; 500 MHz) showed a dynamic behavior of the gallium species 2b but not of compound 2a. The dynamic behavior of 2b was rationalized by assuming that the Ga-N donor bond breaks, inversion at the nitrogen atom occurs, and a rotation of the Me2Ntsi ligand takes place followed by a re-formation of the Ga-N bond on the other side of the gallium atom. The analysis of the signals of meta and ortho protons of 2b gave approximate values of DeltaG not equal of 59.6 and 59.1 kJ mol-1, respectively. Compound 2b reacted with [Pt(PEt3)3] to give the ring-open product [(eta6-C6H6)Mo{eta6-C6H5[GaPh(Me2Ntsi)]}] (3b). The molecular structure of 3b was deduced from a single-crystal X-ray determination. The formation of the unexpected platinum-free product 3b can be rationalized by assuming that benzene reacted with 2b in a 1:1 ratio. Through a series of 1H NMR experiments with 2b it was shown that small amounts of donor molecules (e.g., THF) in benzene are needed to form 3b; in the absence of a donor molecule, 2b is thermally stable.

Synthesis and biological activity of tetralone abscisic acid analogues.

Bicyclic analogues of the plant hormone abscisic acid (ABA) were designed to incorporate the structural elements and functional groups of the parent molecule that are required for biological activity. The resulting tetralone analogues were predicted to have enhanced biological activity in plants, in part because oxidized products would not cyclize to forms corresponding to the inactive catabolite phaseic acid. The tetralone analogues were synthesized in seven steps from 1-tetralone and a range of analogues were accessible through a second route starting with 2-methyl-1-naphthol. Tetralone ABA 8 was found to have greater activity than ABA in two bioassays. The absolute configuration of (+)-8 was established by X-ray crystallography of a RAMP hydrazone derivative. The hydroxymethyl compounds 10 and 11, analogues for studying the roles of 8- and 9-hydroxy ABA 3 and 6, were also synthesized and found to be active.