Abstract  The nasal mucociliazy apparatus is an important component of the airway defenses. Studies were undertaken to determine the nature and distribution of acute effects of inhaled formaldehyde on the nasal mucociliary apparatus of male F-344 rats using whole body exposures. Formaldehyde exposures ranged from a single 6-hr period up to multiple 6-hr exposures daily for 3 weeks, with exposure concentrations of 15, 6, 2, 0.5, and 0 ppm. Within I hr of the last exposure, the rats were kilied and the nasal passages examined for effects on nasal mucociliary function. Exposure to 15 ppm formaldehyde induced inhibition of mucociliary function in specific regions of the nose, and mucostasis was generally more extensive than ciliastasis. These effects, which were initially confined to the anterior regions of the nose, became progressively more extensive for up to 2 weeks of exposure with only very slight progression during the third week. Inhibition of mucociliary function was much less severe with 6 ppm, minimal at 2 ppm, and not detected in rats following exposure to 0.5 ppm. The distribution of epithelial lesions, identified by histopathology, correlated well with the distribution of defective mucociliary function, but mucociliaiy function was a more sensitive indicator of toxicity. Localized defects in mucociliary function represent a potentially important consequence of exposure to formaldehyde.

Abstract  The fact that the chlorinated dioxins are highly toxic, teratogenic, and acnegenic does not of necessity indicate they are carcinogens as well. However, in view of the widespread use of products that might contain dioxins as contaminants and their extreme stability under environmental conditions, examination of their possible long term effects is imperative. This program was initiated to determine the chronic toxicity and potential carcinogenicity of a series of chlorinated dibenzodioxins by oral administration and skin application. The unsubstituted, 2,7 dichloro- and octachlorodibenzodioxins are relatively innocuous with regard to toxicity. The 2,3,7 trichloro-, 2,3,7,8 tetrachloro- and hexachlorodibenzodioxins, however, are quite toxic and require the use of specialized facilities to minimize the possibility of human exposure. This report describes the authors' results to date with the nontoxic dioxins. Work is being initiated with the toxic dioxins as they become available. These preliminary results are by no means conclusive with regard to the carcinogenicity of the chlorinated dioxins. The oral studies indicate primarily hepatotoxicity, expecially in the case of octachlorodibenzodioxin. The skin carcinogenesis assay for the nontoxic compounds is nearing completion, and no skin tumors have been observed in the complete carcinogenesis studies. The nature of the internal growths must still be determined at necropsy.

Abstract  Retinoids are potent forms of vitamin A and are involved in a broad range of physiological processes and the pharmacological effects of retinoids are primarily mediated by the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Several natural and synthetic RAR modulators have proven to be clinically useful for a number of therapeutic indications including cancer, psoriasis, and diabetes. Unfortunately, these agents lead to a number of significant side effects. Most synthetic retinoid ligands are based on the retinoid scaffold and thus have similarities to the natural ligand with all previously disclosed RAR ligands having a carboxylic acid that makes a critical ionic bridge within the ligand binding domain of the receptors. The potential therapeutic value offered from RAR modulation provides the impetus to identify novel ligands based on unique scaffolds that may offer improved toxicity and pharmacokinetic profiles. Here we describe the identification of an atypical RAR inverse agonist that represents the first non-acid, non-retinoid direct modulator of RAR receptor subfamily. SR-0065 functions as a pan-RAR inverse agonist suppressing the basal activity of RARα, RARβ, and RARγ, as well as inhibiting agonist-induced RAR activity. SR-0065 treatment enhanced receptor interaction with a peptide representative of the corepressor SMRT, and in cells SR-0065 enhances recruitment of SMRT to the promoter of the RARγ dependent gene, Cyp26A1. The acid form of SR-0065, SR-1758, was inactive in all assays. Thus, SR-0065 represents a new class of non-acid, non-retinoid RAR modulator that may be used as a point to initiate development of improved RAR-targeted drugs.

Abstract  The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to 1,4-dioxane. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of 1,4-dioxane. The intent of Section 6, Major Conclusions in the Characterization of Hazard and Dose Response, is to present the major conclusions reached in the derivation of the reference dose, reference concentration, and cancer assessment, where applicable, and to characterize the overall confidence in the quantitative and qualitative aspects of hazard and dose response by addressing the quality of the data and related uncertainties. The discussion is intended to convey the limitations of the assessment and to aid and guide the risk assessor in the ensuing steps of the risk assessment process.

Abstract  In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the β-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications.

Abstract  We present a video-densitometric quantification method for benzocaine in lozenges. The quantification is based on a derivatisation reaction with 4-dimethylaminobenzaldehyde. Measurements were carried out using a 16-bit flatbed scanner. Benzocaine was separated to a distance of 50 mm in a vertical developing chamber without vapour saturation. We present an RP-18 phase separation on a cyanopropyl plate (Merck, Darmstadt, Germany) using water, CH3CN, dioxane, ethanol, and NH3 (25 %) (8 + 2 + 1 + 1 + 0.05, v/v) as the mobile phase. We also separated benzocaine in a normal phase system on silica gel 60 LiChrospere(A (R)) plates (Merck, Darmstadt, Germany) with the mobile phase MTBE/cyclohexane (1 + 1, v/v). The calibration functions for benzocaine in both separations were linear in the range from 1 to 1,000 ng per spot. The range of linearity covers two magnitudes of power because the Kubelka-Munk expression was used for data transformation. In the cyanopropyl-system, the benzocaine amount was quantified as 242.5 +/- A 18.2 ng in a spot or 6.86 +/- A 0.52 mg in a single lozenge. The amount of 7.0 mg benzocaine per lozenge was labelled. The combined uncertainty of sample and calibration measurements was statistically calculated using a significance level of alpha = 0.05 to a total relative uncertainty of 7.49 %. The separation method is inexpensive, fast and reliable.

Abstract  Soda lignin, dioxane lignin and milled lignin were isolated from Alfa grass (Stipatenacissima L.). The physico-chemical characterization of three different lignins: one industrial lignin precipitated from soda spent liquor and two lignin preparations isolated under laboratory conditions from Alfa grass (also know as Esparto grass) was performed. The structures of lignins were studied by three non-destructive (FT-IR, solid state (13)C NMR and UV/visible spectroscopy) and two destructive (nitrobenzene oxidation and thermogravimetric analysis) methods. Elemental analysis and the methoxyl content determination were performed in order to determine the C(9) formulae for the studied lignins. The total antioxidant capacity of the studied lignins has been determined and compared to commercial antioxidants commonly used in thermoplastic industry.

Abstract  INTRODUCTION: A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [¹⁸F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT4 in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [¹⁸F]MNI-698.

METHODS: Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [¹⁸F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software.

RESULTS: The radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys' organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq.

CONCLUSION: The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [¹⁸F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [¹⁸F]MNI-698, in order to minimize the subject absorbed doses.

Abstract  The acid-base and complex-formation equilibria of [Ru(H(2)dtpa)(H(2)O)], where dtpa = diethylenetriaminepentaacetate, with a series of bio-relevant ligands having various functional groups, viz. thiol, amine, imidazole and carboxylate, were investigated using potentiometric and spectrophotometric techniques. The pK(a) values for [Ru(H(2)dtpa)(H(2)O)] were found to be 2.28 and 3.48 for the uncoordinated carboxylic acid groups and 8.83 for the coordinated water molecule. The complexes formed are of 1:1 stoichiometry and their formation-constants were determined. The effect of dioxane on the acid-base and complex-formation equilibria of the Ru(III) complex was studied. The displacement reaction of coordinated NO by the investigated ligands showed that thiols can compete with NO in their reaction with [Ru(III)(dtpa)(H(2)O)](2-). The results reveal that the Ru(III) complex is deactivated as a NO scavenger by thiolate ligands.

Abstract  Delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality for patients surviving the rupture of an intracranial aneurysm. Despite an association between vasospasm and DCI, thrombosis and thromboembolism may also contribute to DCI. In this study we investigate the time course of intravascular microclot formation after experimental subarachnoid hemorrhage (SAH) and assess the effects of the following two drugs on microclot burden: mutant thrombin-activated urokinase-type plasminogen activator (scFv/uPA-T), which is bound to red blood cells for use as a thromboprophylactic agent, and clazosentan, an endothelin antagonist. In the first study, adult male C57BL/6 mice were sacrificed at 24 (n=5), 48 (n=6), 72 (n=8), and 96 (n=3) hours after SAH induced by filament perforation of the anterior cerebral artery. Sham animals (n=5) underwent filament insertion without puncture. In the second study, animals received scFv/uPA-T (n=5) 3 hours after hemorrhage, clazosentan (n=5) by bolus and subcutaneous pump after SAH just prior to skin closure, or a combination of scFv/uPA-T and clazosentan (n=4). Control (n=6) and sham (n=5) animals received saline alone. All animals were sacrificed at 48 hours and underwent intra-cardiac perfusion with 4% paraformaldehyde. The brains were then extracted and sliced coronally on a cryostat and processed for immunohistochemistry. An antibody recognizing thrombin-anti-thrombin complexes was used to detect microclots on coronal slices. Microclot burden was calculated for each animal and compared among groups. Following SAH, positive anti-thrombin staining was detected bilaterally in the following brain regions, in order of decreasing frequency: cortex; hippocampus; hypothalamus; basal ganglia. Few microclots were found in the shams. Microclot burden peaked at 48 hours and then decreased gradually. Animals receiving scFv/uPA-T and scFv/uPA-T+clazosentan had a lower microclot burden than controls, whereas animals receiving clazosentan alone had a higher microclot burden (p<0.005). The overall mortality rate in the time course study was 40%; mortality was highest among control animals in the second study. Intravascular microclots form in a delayed fashion after experimental SAH. Microclots may be safely reduced using a novel form of thromboprophylaxis provided by RBC-targeted scFv/uPA-T and represent a potential target for therapeutic intervention in the treatment of DCI.

Abstract  5-(Hetero)aryl-3-(4-carboxamidophenyl)-2-aminopyridine inhibitors of CHK2 were identified from high throughput screening of a kinase-focussed compound library. Rapid exploration of the hits through straightforward chemistry established structure-activity relationships and a proposed ATP-competitive binding mode which was verified by X-ray crystallography of several analogues bound to CHK2. Variation of the 5-(hetero)aryl substituent identified bicyclic dioxolane and dioxane groups which improved the affinity and the selectivity of the compounds for CHK2 versus CHK1. The 3-(4-carboxamidophenyl) substituent could be successfully replaced by acyclic omega-aminoalkylamides, which made additional polar interactions within the binding site and led to more potent inhibitors of CHK2. Compounds from this series showed activity in cell-based mechanistic assays for inhibition of CHK2.

Abstract  Ion mobility and mass spectrometry measurements have been used to examine the populations of different solution structures of the nonapeptide bradykinin. Over the range of solution compositions studied, from 0:100 to 100:0 methanol:water and 0:100 to 90:10 dioxane:water, evidence for 10 independent populations of bradykinin structures in solution is found. In some solutions as many as eight structures may coexist. The solution populations are substantially different than the gas-phase equilibrium distribution of ions, which exhibits only three distinct states. Such a large number of coexisting structures explains the inability of traditional methods of characterization such as nuclear magnetic resonance spectroscopy and crystallography to determine detailed structural features for some regions of this peptide.

Abstract  "Push-pull" purines have been synthesized by the introduction of electron-accepting functional groups (A = CN, CO(2)Me, and CONHR) to the heterocyclic C(8) position to complement typical electron-donating substituents at C(2) (D(1)) and C(6) (D(2)). The donor-acceptor purines show significantly altered, and overall improved photophysical properties relative to their acceptor-free precursors (A = H); these include red-shifted (20-50 nm) absorption maxima, highly solvatochromic emission profiles (em lambda(max) from 355-466 nm depending on substitution pattern and solvent) with excellent linear correlations between emission energy and solvent polarity (E(T)(N)), improved photochemical stability upon continuous irradiation, and enhanced (up to 2500%) fluorescence quantum yields. Comprehensive structure-property studies show how the absorption/emission maxima and quantum yields depend on donor and acceptor structure, relative donor position (C(2) or C(6)), and solvent (1,4-dioxane, dichloromethane, acetonitrile, methanol, and in some cases water). Further insight regarding electronic structure comes from a quantitative treatment of the solvent-dependent emission data (that provides Delta mu(ge) values ranging from 1.9 to 3.4 D) and DFT (B3LYP/6-311++G**) electronic structure calculations. X-ray crystal structures of several derivatives showcase the molecular recognition capabilities of the donor-acceptor chromophores that overall have photophysical and structural properties suitable for applications in biosensing and materials.

Abstract  A new synthetic route to 2,2-bis(sulfanylmethyl)propane-1,3-diol, (II), is described starting from the commercially available 2,2-bis(hydroxymethyl)propane-1,3-diol. The structures of two intermediates on this route are described. 5,5-Dimethenyl-2,2-dimethyl-1,3-dioxane bis(thiocyanate) (systematic name: {[5-(cyanosulfanyl)-2,2-dimethyl-1,3-dioxan-5-yl]sulfanyl}formonitrile), C(10)H(14)N(2)O(2)S(2), (X), crystallizes in the space group P2(1)/c with no symmetry relationship between the two thiocyanate groups. There is a short intramolecular N...S contact for one thiocyanate group, while the second group is positioned such that this type of interaction is not possible. 1,3-(Hydroxymethyl)propane-1,3-diyl bis(thiocyanate), C(7)H(10)N(2)O(2)S(2), (XI), also features a single short N···S contact in the solid state. Hydrogen bonding between two molecules of compound (XI) results in the formation of dimers in the crystal, which are then linked together by a second hydrogen-bond interaction between the dimers. In addition, the structures of two intermediates from an unsuccessful alternative synthesis of (II) are reported. 2,2-Bis(chloromethyl)propane-1,3-diol, C(5)H(10)Cl(2)O(2), (VI), crystallized as an inversion twin with a minor twin fraction of 0.43 (6). It forms a zigzag structure as a result of intermolecular hydrogen bonding. The structure of 9,9-dimethyl-2,4,8,10-tetraoxa-3λ(4)-thiaspiro[5.5]undecan-3-one, C(8)H(14)O(5)S, (VII), shows evidence for a weak S···O contact with a distance of 3.2529 (11) Å.

Abstract  New 17-picolyl and 17-picolinylidene androstane derivatives, 3-10, 15, 18, 19, 22 and 23, were synthesized starting from 17α-picolyl-androst-5-en-3β,17β-diol (1) and 17(Z)-picolinylidene-androst-5-en-3β-ol (2). Reaction of 1 with m-chloroperoxybenzoic acid gives 5α,6α-epoxy N-oxide derivative 3, or, with Jones reagent, 3,6-dione derivative 4; while 17α-picolyl-androst-5-en-3β,4α,17β-triol (5) or 3β,4β,17β-triol (6) derivatives are obtainable from 1 using SeO(2) in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10. Oppenauer oxidation of 1 and 2 yields 4-en-3-one derivatives 11 and 12, which, with H(2)O(2) in 4 M NaOH, affords 4α,5α and 4β,5β-epoxides 13, 14, 16 and 17. New 4-methoxy-3-keto derivatives 15 and 18 were obtained from 13 and 14, or, with methanol in 4 M NaOH, from 16 and 17. Reduction of 11 with NaBH(4) gives 22, which was then acetylated to obtain 23. All new derivatives were screened for antitumor activity against human breast adenocarcinoma ER+, MCF-7; human breast adenocarcinoma ER-, MDA-MB-231; prostate cancer AR-, PC-3; human cervix carcinoma, HeLa; and colon cancer, HT-29 cells; as well as one human non-tumor cell line, MRC-5. Compounds 3, 5, 6, 8, 10, 18, 19 and 22 exhibited significant antitumor activity against MDA-MB-231 breast cancer cells; while 5, 6 and 10 also showed strong cytotoxicity against HT-29. Only compound 19 exhibited significant activity against MCF-7 breast cancer cells. No compounds displayed cytotoxicity against non-tumor MRC-5 cells.

Abstract  Six hybrid N-ureidoethylamides of octapeptides in which an N-terminal cyclic structure related to enkephalin was elongated by a C-terminal fragment of deltorphin were synthesized on MBHA resin. The synthetic procedure involved deprotection of Boc groups with HCl/dioxane and cleavage of the peptide resin with 45 % TFA in DCM. d-Lys and d-Orn were incorporated in position 2, and Lys, Orn, Dab, or Dap in position 5. The side chains of the dibasic amino function were protected with the Fmoc group. This protection was removed by treatment with 55 % piperidine in DMF, and cyclization was achieved by treatment with bis-(4-nitrophenyl)carbonate. Using various combinations of dibasic amino acids, peptides containing a 17-, 18-, 19- or 20-membered ring structure were obtained. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse opioid activities were observed, depending on the size of the ring. Extension of the enkephalin sequence at the C-terminus by a deltorphin fragment resulted in a change of receptor selectivity in favor of the δ receptor. The conformational propensities of selected peptides were determined using the EDMC method in conjunction with data derived from NMR experiments carried out in water. This approach allowed proper examination of the dynamical behavior of these small peptides. The results were compared with those obtained earlier with corresponding N-(ureidoethyl)pentapeptide amides.

Abstract  1,4-Dioxane, is a synthetic organic compound used widely throughout industry as a solvent. 1,4-Dioxane causes liver damage and kidney failure and has been shown to be carcinogenic to animals, and is a potential carcinogen to humans. Its recalcitrant nature means that conventional water treatment methods are ineffective in removing it from water. A class of technologies called advanced oxidation technologies has been shown to completely mineralise 1,4-dioxane. In this study the effects of pH on TiO(2) photocatalysis reactor systems were investigated. pH was found to significantly affect the efficiencies of these processes with neutral pH conditions the most effective.

Abstract  A novel, standardized geometry of the human nasal cavity was created by aligning and processing 30 sets of computed tomography (CT) scans of nasal airways of healthy subjects. Digital three-dimensional (3-D) geometries of the 60 single human nasal cavities (30 right and 30 mirrored left cavities) were generated from the CT scans and measurements of physical parameters of each single nasal cavity were performed. A methodology was developed to scale, orient, and align the nasal geometries, after which 2-D digital coronal cross-sectional slices were generated. With the use of an innovative image processing algorithm, median cross-sectional geometries were created to match median physical parameters while retaining the unique geometric features of the human nasal cavity. From these idealized 2-D images, an original 3-D standardized median human nasal cavity was created. This new standardized geometry was compared against the original geometries of all subjects as well as limited existing data from the literature. The new model has potential for use as a geometric standard in future experimental and numerical studies of deposition of inhaled aerosols, as well as for use as a reference during diagnosis of unhealthy patients. The specific procedure developed could also be applied to build standard nasal geometries for different identifiable groups within the larger population.

Abstract  A bottom-up approach is presented here for morphology control of Ln-asparagine (Asn) coordination polymers (CPs) from the macro to nanoscopic regime by tuning solvent polarity based on the π* solvent polarity scale in polar solvent-water mixed solutions. By a simple hydrothermal treatment, large macroporous spheres with sizes up to millimeters were obtained in ethanol (π*: 0.54)-water mixtures, and their formation mechanism was proved to be particle aggregation together with a hollowing process based on Ostwald ripening. Other solvents with increasing polarity were also used, and submicrometer spheres as well as fine nanoparticles were prepared in acetone (π*: 0.71) and DMF (π*: 0.88), respectively. When dioxane (π*: 0.55) was used here, whose π* value is similar to ethanol, large macroporous spheres were also prepared. Furthermore, with Ce- and La-Asn CPs large spheres as precursors, after calcination, ceria and lanthana large spheres with hierarchical structures were fabricated, respectively. Considering that many growth media of CPs are single solvent systems, designing certain solvents mixtures and tuning their polarity would bring us new opportunities to achieve morphology and composition control of CPs materials.

Abstract  The quenching of pyrene and 1-methylpyrene fluorescence by nitroanilines (NAs), such as 2-, 3-, and 4-nitroaniline (2-NA, 3-NA, and 4-NA, respectively), 4-methyl-3-nitroaniline (4-M-3-NA), 2-methyl-4-nitroaniline (2-M-4-NA), and 4-methyl-3,5-dinitroaniline (4-M-3,5-DNA), are studied in toluene and 1,4-dioxane. Steady-state fluorescence data show the higher efficiency of the 4-NAs as quenchers and fit with a sphere-of-action model. This suggests a 4-NA tendency of being in close proximity to the fluorophore, which could be connected with their high polarity/hyperpolarizability. In addition, emission and excitation spectra evidence the formation of emissive pyrene-NA ground-state complexes in the case of the 4-NAs and, in a minor degree, in the 2-NA. Moreover, time-resolved fluorescence experiments show that increasing amounts of NA decrease the pyrene fluorescence lifetime to a degree that depends on the NA nature and is larger in the less viscous solvent (toluene). Although the NA absorption and the pyrene (Py) emission overlap, we found no evidence of dipole-dipole energy transfer from the pyrene singlet excited state ((1)Py) to the NAs; this could be due to the low NA concentration used in these experiments. Transient absorption spectra show that the formation of the pyrene triplet excited state ((3)Py) is barely affected by the presence of the NAs in spite of their efficiency in (1)Py quenching, suggesting the involvement of (1)Py-NA exciplexes which--after intersystem crossing--decay efficiently into (3)Py.

Abstract  Binary complexes of L-glutamic acid with toxic metal ions such as Pb(II), Cd(II) and Hg(II) in 0.0-60.0% v/v 1,4 dioxan-water media at 303.0 K and an ionic strength of 0.16 mol dm(-3) of sodium nitrate has been studied pH-metrically. The active forms of ligand are LH3, LH2 and LH. The best fit chemical models are chosen based on statistical parameters like crystallographic R-factor, X-2, skewness and kurtosis. The predominant species detected are ML2H4, ML2H3, ML2H2, ML2 and ML. Models containing different numbers of species were refined by using the computer program MINIQUAD75. The trend in variation of complex stability constants with changes in the dielectric constant of the medium is explained on the basis of electrostatic and non-electrostatic forces. The species distribution with pH at different compositions of dioxan-water mixture and plausible equilibria for the formation of species are also presented.

Abstract  A series of zinc complexes based on asymmetrical N,N,O-tridentate ligands were prepared via binaphthyl diamine derivatives. These complexes were characterized and employed as catalysts in lactide polymerization. The X-ray diffraction analyses revealed that molecular structures of 1b and 2b were mononuclear complexes with zinc atoms in distorted octahedral geometries. Upon co-catalysis with isopropanol, complex 2a showed the highest activity among these zinc complexes for the ring-opening polymerization of L-lactide, and complex 3a exhibited the highest stereoselectivity for the ring-opening polymerization of rac-lactide affording substantially isotactic polylactide (PLA) with a P(m) of 0.62. The polymerization kinetics using 2a as a catalyst was studied in detail. The kinetics of the polymerization results revealed that the rates of polymerization were first-order both in the monomer and the catalyst, and there was a linear relationship between the L-LA conversion and the number-average molecular weight of PLA with a narrow molecular distribution (1.07-1.17). The activation energy (31.49 kJ mol(-1)) was deduced according to the Arrhenius equation.