Synthesis of an allyl carbonate monomer as alternative to TEGDMA in the formulation of dental composite resins.

Over the past years, significant effort has been dedicated to synthesizing low-shrinking formulations, however, development of dental composites with low volumetric shrinkage continues to be challenging. The purpose of this study was to synthesize a bisphenol allylic derivate (BPhADAC) and evaluate its inclusion in the formulation of a photopolymerizable dental composite resin, as a BisGMA diluent. Experimental (BisGMA/BPhADAC) and control (BisGMA/TEGDMA) photopolymerizable composites were prepared. Double bond conversion, polymerization kinetics, volumetric shrinkage, water sorption, solubility, and flexural properties were investigated. The experimental composite showed higher degree of conversion values, less volumetric shrinkage and less water sorption than the control composite (p < 0.05). In addition, flexural strength between the materials was found to be similar. The overall properties prove that the allylic monomer BPhADAC could be potentially useful in the formulation of low-shrinking dental composite resins.

Chemistry of Fluorinated Carbon Acids: Synthesis, Physicochemical Properties, and Catalysis.

The bis[(trifluoromethyl)sulfonyl]methyl (Tf2CH; Tf=SO2CF3) group is known to be one of the strongest carbon acid functionalities. The acidity of such carbon acids in the gas phase is stronger than that of sulfuric acid. Our recent investigations have demonstrated that this type of carbon acids work as novel acid catalysts. In this paper, recent achievements in carbon acid chemistry by our research group, including synthesis, physicochemical properties, and catalysis, are summarized.

Carbonic acid formation from reaction of carbon dioxide and water coordinated to Al(OH)3: a quantum chemical study.

Density functional and ab initio calculations have been performed on CO(2)-nH(2)O and Al(OH)(3)-CO(2)-nH(2)O (where n = 1, 2, 3) cluster models to elucidate the catalytic effect of a hydroxylated metal center on the formation of carbonic acid (H(2)CO(3)). B3LYP/6-311++G(d,p)-calculated geometries and RI-SCS-MP2/aug-cc-pVTZ//B3LYP/6-311++G(d,p)-calculated energies with respect to isolated gas-phase molecules and various H(2)O, CO(2), and H(2)CO(3)-Al(OH)(3) complexes are presented. It is shown here that H(2)CO(3) formation proceeds via direct CO(2) and nH(2)O reaction with very high activation barriers in the gas phase, 51.40, 29.64, and 19.84 kcal/mol for CO(2)-H(2)O, CO(2)-2H(2)O, and CO(2)-3H(2)O clusters, respectively, decreasing in magnitude with an increase in the number of H(2)O molecules. The energetics as well as the reaction mechanism and energy landscape change significantly when carbonic acid is formed from CO(2) and nH(2)O in the presence of Al(OH)(3), a hydroxylated metal center. Results presented here show important details of the influence of the coordinating metal center in the formation of H(2)CO(3).

Mechanism of the hydration of carbon dioxide: direct participation of H2O versus microsolvation.

Thermochemical parameters of carbonic acid and the stationary points on the neutral hydration pathways of carbon dioxide, CO 2 + nH 2O --> H 2CO 3 + ( n - 1)H 2O, with n = 1, 2, 3, and 4, were calculated using geometries optimized at the MP2/aug-cc-pVTZ level. Coupled-cluster theory (CCSD(T)) energies were extrapolated to the complete basis set limit in most cases and then used to evaluate heats of formation. A high energy barrier of approximately 50 kcal/mol was predicted for the addition of one water molecule to CO 2 ( n = 1). This barrier is lowered in cyclic H-bonded systems of CO 2 with water dimer and water trimer in which preassociation complexes are formed with binding energies of approximately 7 and 15 kcal/mol, respectively. For n = 2, a trimeric six-member cyclic transition state has an energy barrier of approximately 33 (gas phase) and a free energy barrier of approximately 31 (in a continuum solvent model of water at 298 K) kcal/mol, relative to the precomplex. For n = 3, two reactive pathways are possible with the first having all three water molecules involved in hydrogen transfer via an eight-member cycle, and in the second, the third water molecule is not directly involved in the hydrogen transfer but solvates the n = 2 transition state. In the gas phase, the two transition states have comparable energies of approximately 15 kcal/mol relative to separated reactants. The first path is favored over in aqueous solution by approximately 5 kcal/mol in free energy due to the formation of a structure resembling a (HCO 3 (-)/H 3OH 2O (+)) ion pair. Bulk solvation reduces the free energy barrier of the first path by approximately 10 kcal/mol for a free energy barrier of approximately 22 kcal/mol for the (CO 2 + 3H 2O) aq reaction. For n = 4, the transition state, in which a three-water chain takes part in the hydrogen transfer while the fourth water microsolvates the cluster, is energetically more favored than transition states incorporating two or four active water molecules. An energy barrier of approximately 20 (gas phase) and a free energy barrier of approximately 19 (in water) kcal/mol were derived for the CO 2 + 4H 2O reaction, and again formation of an ion pair is important. The calculated results confirm the crucial role of direct participation of three water molecules ( n = 3) in the eight-member cyclic TS for the CO 2 hydration reaction. Carbonic acid and its water complexes are consistently higher in energy (by approximately 6-7 kcal/mol) than the corresponding CO 2 complexes and can undergo more facile water-assisted dehydration processes.

Synthesis and transdermal penetration-enhancing activity of carbonic and carbamic acid esters--comparison with transkarbam 12.

Transkarbam 12 (T12) is a novel transdermal penetration enhancer with high activity. Its polar head group is formed by carbamic acid salt that is unstable in acidic environment and releases CO(2). To find out whether this property influences its high activity, two series of compounds with CO(2) stronger bound in the polar head have been prepared-carbonic and carbamic acid esters. The carbamate salt in the polar head was found to be essential for the enhancing activity and its decomposition in an acidic environment suggested relating to the mode of action of T12.

Production of oxidants by ion irradiation of water/carbon dioxide frozen mixtures.

We present new experimental results on the formation of oxidants, such as hydrogen peroxide, ozone, and carbonic acid, under ion irradiation of icy mixtures of water/carbon dioxide at different ratios and temperatures (16 and 80 K). Pure water ice layers and mixtures with carbon dioxide were irradiated by 200 keV He+ ions. We found that the CO(2)/H(2)O ratio progressively decreased to a value of about 0.1, the H(2)O(2) production increased with increasing CO(2) abundance at both 16 and 80 K, and the CO and H(2)CO(3) production increased with increasing CO(2) abundance at 16 K. At 80 K, the synthesis of CO was less efficient because of the high volatility of the molecule that partially sublimed from the target. The production of carbonic acid was connected with the production of CO(3). O(3) was detected only after ion irradiation of CO(2)-rich mixtures. The experimental results are discussed with regard to the relevance they may have in the production of an energy source for a europan or a martian biosphere.

Synthesis and conformational study of 3,4-carbocyclic bridged indole melatonin and serotonin analogues.

Tetrahydrobenz[cd]indole, has been usually assumed to be a rigid scaffold of arylethylamines of pharmaceutical interest, such as melatonin and serotonin. A series of molecules containing this scaffold has been synthesized and their conformation in solution has been determined by 1H NMR. The values of the coupling constants show that the carbocycle fused with the indole ring is a mixture of the two conformers with substituent in equatorial or axial orientation. The molar fraction of the conformers appears to be sensibly affected by the bulkiness of the C-2 indole substituent. A pseudo-axial orientation of the C-3 alkylamido side chain is important for melatonin ligands to access the binding site and exhibit potent in vitro affinity, as illustrated for melatonin ligand 1 (pK(i)=9.32).

Protein carbonyl formation on mucosal proteins in vitro and in dextran sulfate-induced colitis.

Reactive oxygen and nitrogen species have been implicated as mediators of mucosal injury in inflammatory bowel disease, but few studies have investigated protein oxidation in the inflamed mucosa. In this study, protein carbonyl formation on colonic mucosal proteins from mice was investigated following in vitro exposure of homogenates to iron/ascorbate, hydrogen peroxide, hypochloric acid (HOCl), or nitric oxide (*NO). Total carbonyl content was measured spectrophotometrically by derivatization with dinitrophenylhydrazine (DNPH), and oxidation of component proteins within the tissue was examined by Western blotting for DNPH-derivatized proteins using anti-dinitrophenyl DNP antibodies. These results were compared with protein carbonyl formation found in the acutely inflamed mucosa from mice with colitis induced by dextran sulfate sodium (DSS) administered at 5% w/v in the drinking water for 7 d. In vitro, carbonyl formation was observed after exposure to iron/ascorbate, HOCl and *NO. Iron/ascorbate (20 microM/20 mM) exposure for 5 h increased carbonyl groups by 80%, particularly on proteins of 48, 75-100, 116, 131, and 142 kDa. Oxidation by 0.1 and 0.5 mM HOCl did not increase total carbonyl levels, but Western blotting revealed carbonyl formation on many proteins, particularly in the 49-95 kDa region. After exposure to 1-10 mM HOCl, total carbonyl levels were increased by 0.5 to 12 times control levels with extensive cross-linking and fragmentation of proteins rich in carbonyl groups observed by Western blotting. In mice with acute colitis induced by DSS, protein carbonyl content of the inflamed mucosa was not significantly different from control mucosa, (7.80 +/- 1.05 vs. 8.43 +/- 0.59 nmo/mg protein respectively, p = .16 n = 8, 10); however, Western blotting analysis indicated several proteins of molecular weight 48, 79, 95, and 131 kDa that exhibited increased carbonyl content in the inflamed mucosa. These proteins corresponded to those observed after in vitro oxidation of normal intestinal mucosa with iron/ ascorbate and HOCl, suggesting that both HOCl and metal ions may be involved in protein oxidation in DSS-induced colitis. Identification and further analysis of the mucosal proteins susceptible to carbonyl modification may lead to a better understanding of the contribution of oxidants to the colonic mucosa tissue injury in inflammatory bowel disease.

N-(2-hydroxybenzyl)-omega-amino carbonic acids and their derivatives as tools for biochemical and biophysical investigations.

We propose N-(2-hydroxybenzyl)-omega-amino carbonic acids (An) as multifunctional probes for fatty acid metabolism studies. Multifunctionality could be achieved by introduction of different isotopes into An molecule. Deuteration of An results in probes for 2H-NMR membrane studies. Introduction of radioactive iodine and bromine isotopes into An gives diagnosticums for gamma-tomography and PET. AnI and AnBr are fluorescence quenchers usable for membrane studies. This multifunctionality of An derivatives is valuable because they participate in such metabolic pathways of fatty acids as beta-oxidation and inclusion into lipids. They can also inhibit natural FA oxidation.

[Synthesis of 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones as well as 2-substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles and 3-carbonic acid amides, respectively, and testing their cardiovascular activity]. / Synthese von 3-Cyan-6-methyl-4-pyridyl-2(1H)-pyridinthionen sowie neuer in 2-Stellung substituierter 6-Methyl-4-pyridyl-pyridin-3-carbonitrile bzw. -3-carbonsäureamide und deren Prüfung auf kardiovaskuläre Wirksamkeit.

By the base catalyzed reaction of our previously described 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones 1 and 2, respectively, with branched and unbranched, respectively, alkyl, aralkyl-, alkinyl-, hydroxyalkyl-, ethoxycarbonyl- and carbamoylalkylhalides the new in 2-position substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles 15-30 were formed. By means of oxidation of the 2-methylthio-substituted pyridine-3-carbonitriles 3 and 4 with potassium periodate and potassium permanganate in diluted acetic acid, respectively, the sulfinyl compounds 5 and 6, respectively, and the sulfonyl compounds 7 and 8, respectively, were prepared. By heating of 3 and 4, respectively, with concentrated sulphuric acid the 2-methylthio-pyridine-3-carboxamides 9 and 10 were obtained. The oxidation of these compounds with potassium periodate and potassium permanganate, respectively, had yield the pyridines 11 and 12, respectively, as well as 13 and 14, respectively.

Preparation and properties of some crystalline symmetrical anhydrides of N alpha-tert.-butyloxycarbonyl-amino acids.

The preparation and properties of 16 crystalline symmetrical anhydrides of N alpha-tert.-butyloxycarbonyl-amino acids is described.

Synthesis, pharmacologic and toxicologic study of carbonic and carbamic acid esters.

The results of the pharmacologic study of some synthesized derivatives of carbamic and carbonic acids show that the compounds are biologically active. They are less toxic than imipramine, and exert a marked excitation effect on the central nervous system. Some of the compounds (including PS-1, P-8-Y and PS-4) possess greater antidepressive action than imipramine.