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Preparation of calcium aluminate cement for hard tissue repair: effects of lithium fluoride and maleic acid on setting behavior, compressive strength, and biocompatibility.

We investigated lithium fluoride (LiF) and maleic acid (MA) containing calcium aluminate cement (CAC) for hard tissue repair. The objective of this study is to estimate the addition effects of LiF and MA on setting behavior, compressive strength, and biocompatibility of CAC and to find the most compatible composition of LiF and MA for using CAC as a new bone cement. The CAC was composed mainly of CaO. Al(2)O(3). Samples of LiF and MA containing CAC were formed along with recording of setting time and peak temperature and then set cement was analyzed by X-ray diffraction (XRD). Agar diffusion test, tetrazolium bromide (MTT) assay, and hemolysis test were used to detect initial in vitro biocompatibility of LiF and MA containing CAC. It was revealed from the results that LiF shortened setting time and decreased compressive strength, whereas MA delayed setting time and increased compressive strength. However, LiF and MA showed no or little influence on maximum temperature of CAC. CAC containing 0.5 g of LiF and 8.75 g of MA showed the highest compressive strength (111.64 +/- 7.74 MPa) across all the experimental compositions. The CACs containing 0.5 g of LiF/8.75 g of MA and 1.01 g LiF/8.75 g of MA had no cytotoxicity and hemolysis. In this study, CAC with 0.5 g of LiF and 8.75g of MA showed the most compatible properties for using bone cement, and thus it was assessed a candidate for a new bone cement along with CAC.

Aluminum Compounds↗

In vitro study of local solubility of uric acid stones with lithium carbonate.

The possibilities of local dissolution of uric acid calculi with Na hydrocarbonate, K carbonate and lithium carbonate were examined in vitro. The most promising results were obtained with lithium carbonate. The necessity for studies of the compound in laboratory animals before its use in humans is emphasized.

Bicarbonates↗

Racemic N-aryl bis(amidines) and bis(amidinates): on the trail of enantioselective organolanthanide catalysts.

A series of racemic N-aryl-substituted trans-1,2-diaminocyclohexyl (t-1,2-DACH)-linked bis(amidines) were synthesised and their solution behaviour, and solid-state structures were investigated. The amidine functionalities within these compounds were extremely sterically hindered, with ortho-aryl substitution found to hinder N-Ar bond rotation. The results of these studies were used to rationalise the lack of reactivity of these compounds with [Y{N(SiMe(3))(2)}(3)]. Dilithiation of the t-1,2-DACH linked bis(amidines) did, however, proceed easily and the solution behaviour and solid-state structures of the resulting THF-solvated lithium amidinates were investigated. All the compounds showed similar structures in the solid-state, while NMR experiments indicated that the solid-state structures were likely to be maintained in solution. Attempted metathesis reactions with YCl(3) did not, however, yield the desired yttrium chloride complexes.

Amidines↗

Probing the structure and stability of the tumor-localizing derivative of hematoporphyrin by reductive cleavage with LiAlH4.

A procedure involving the use of the reducing agent lithium aluminum hydride (LiAlH4) has been designed to explore the nature of the oligomer linkages in the tumor-localizing component of hematoporphyrin derivative (HPD). High-performance liquid chromatography and fast-atom bombardment mass spectrometry were used to determine the reduction products. The results are consistent with a structure wherein ester linkages join hematoporphyrin molecules. The presence of minor amounts of ether-linked porphyrins was confirmed, and their origin was determined through the application of the chemical reduction process to HPD. An increased proportion of ether-linked porphyrins was detected during storage of HPD at room temperature or above. The commercial product Photofrin II, presumably an HPD preparation enriched in the dimer/oligomer fraction, was found to contain approximately 50% ether linkages. This product therefore differs from the corresponding fraction of freshly prepared HPD.

Aluminum↗

Cycloadditions of 2-azaallyllithium species with conjugated polyenes.

2-Azaallyllithium species [R(1)CH(-)N=C(X)R(2)Li(+), where R(1) and R(2) are alkyl and X = OMe] were generated by tin-lithium exchange of (2-azaallyl)stannanes and underwent [pi4s+pi2s] and [pi6s+pi4s] cycloadditions with cyclic dienes and trienes, respectively, to generate novel bridged azabicyclic compounds in a highly diastereoselective endo fashion. The periselectivity using cycloheptatriene was modest, producing a 1:1 mixture of [pi6s+pi4s] and [pi4s+pi2s] adducts. The reactions of 2-azaallyllithium species with dienes proceeded by a [pi4s+pi2s] pathway. The cycloadducts derived from cyclic 2-azaallyllithium species possess the 7-azabicyclo[2.2.1]heptane (tropane) or 8-azabicyclo[3.2.1]octane ring system and have been elaborated into cocaine-like analogues.

Aza Compounds↗

Synthesis of 6-deoxy-5-thio-D-glucose.

Three routes were investigated for the conversion of D-glucose into the title compound. In the first approach, reduction of the 5,6-thiirane ring of 5,6-dideoxy-5, 6-epithio-1,2-O-isopropylidene-alpha-D-glucofuranose (17) as well as that of its 3-O-allyl derivative (13) with lithium aluminium hydride was investigated; 17 afforded the corresponding 6-deoxy derivative besides di-, tri-, and poly-mers, whereas only polymers were formed from 13. In the second approach, the oxirane ring of 3-O-allyl-5,6-anhydro-1,2-O-isopropylidene-beta-L-idofuranose was reduced by sodium borohydride and the resulting 6-deoxy derivative was converted into the 5-thiobenzoate; the corresponding hex-4-enofuranose was formed as a byproduct. In the third approach partial mesylation of methyl 5-thio-alpha-D-glucopyranoside was attempted, but the 6-mesylate 27 could be isolated only in modest yield (28%) together with rearranged 2,5-thioanhydromannofuranoside derivatives. The mechanism of this rearrangement is discussed in detail. The 6-mesylate 27 was converted via the 6-iodo derivative into the title compound.

Aluminum Compounds↗

Odor and taste aversions conditioned in anesthetized rats.

Conditioned flavor aversions (CFA) are acquired by anesthetized rats but effects of various anesthetics on acquisition of aversions for separate odor and taste components are unknown. In Experiment 1, rats drank tomato juice and then were tranquilized with "Innovar-Vet" or "Rompun" before receiving injections of lithium chloride. Neither drug interfered with acquisition of aversions. Innovar-Vet alone produced no aversions; Rompun alone produced mild aversions but did not enhance aversions when combined with lithium. In Experiments 2 and 3, rats received a compound odor/taste cue as they drank and then were anesthetized with pentobarbital before lithium injections. Anesthesia alone produced negligible aversions but facilitated taste-lithium aversions. During odor tests, odor aversions were weaker than taste aversions. These data extend previous work and suggest that CFA does not result from ordinary classical conditioning. A tripartite notation that unites CFA and classical conditioning is discussed.

Anesthetics↗

Characterization of an antibiotic produced by a strain of Pseudomonas fluorescens inhibitory to Gaeumannomyces graminis var. tritici and Pythium spp.

The production, isolation, and characterization of an antibiotic substance from cultures of Pseudomonas fluorescens 2-79 (NRRL B-15132) is described. P. fluorescens 2-79 originally was isolated from the roots of wheat and is suppressive to the wheat root disease take-all caused by Gaeumannomyces graminis var. tritici. The antibiotic was isolated from potato glucose broth cultures of strain 2-79 by solvent extraction. It was purified by silica gel column chromatography and was a greenish yellow, needle-shaped crystal with a melting point of 242 degrees C (decomposition). It was soluble in methylene chloride, chloroform, acetone, 2 N sodium hydroxide, and 2 N hydrochloric acid and was insoluble in water, methanol, ethyl acetate, tetrahydrofuran, diethyl ether, carbon tetrachloride, hexane, and petroleum ether. On the basis of UV, infrared, 1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, mass spectral analysis, and elemental analysis, the structure of the antibiotic is proposed to be a dimer of phenazine carboxylic acid. Lithium aluminum hydride reduction of the antibiotic yielded hydroxymethyl phenazine as a major product which retained most of the biological characteristics of the parent molecule. There were no toxic symptoms when mice received this antibiotic by oral doses up to 464 mg/kg. The antibiotic showed excellent activity against several species of fungi, including the wheat pathogens Gaeumannomyces graminis var. tritici, Rhizoctonia solani, and Pythium aristosporum; and it may have a role in suppression of take-all in vivo by strain 2-79.

Aluminum↗

The action of local anaesthetics on the compound action potential is altered by the nature of the permeant ion in frog nerve.

Compound action potentials were recorded from the isolated frog sciatic nerve using either sodium or lithium as the permeant ion, and an assessment of the action of local anaesthetics was made. The compound action potentials evoked from the nerve were not different in terms of their mean amplitude or time to peak whether recorded with sodium or lithium as the permeant ion. The local anaesthetics tested, procaine, lignocaine and benzocaine, were more potent, as measured by their IC50 values, by 2.3, 2.1 and 1.8 times, respectively, when lithium rather than sodium was used as the permeant ion. The sensitivity of the nerves to tetrodotoxin was not significantly different whether sodium or lithium was used as the permeant ion. The slope of the concentration inhibition curves was not significantly altered in the presence of sodium or lithium for any of the compounds tested. These results are consistent with the idea that the binding site for local anaesthetics is intimately associated with the pore region of the channel and that the nature of the permeant ion can alter the interaction of the drugs with the sodium channel. However, since this is not a common feature of all compounds which block sodium channels by interacting at the pore, it may help refine the existing structural models of sodium channels.

Action Potentials↗

Synthesis of Indium Amide Compounds.

Indium trichloride reacts with 3 equiv of lithium amide in diethyl ether to give In(NRR')(3) (R = Ph or t-Bu, R' = SiMe(3); R = t-Bu, R' = SiHMe(2)) and with 3 or 4 equiv of LiNMe(SiMe(3)) to yield Li[In{NMe(SiMe(3))}(4)]. The chloride also reacts with LiNPh(2) in THF to give the salt Li[In(NPh(2))(3)Cl] and with LiNRR' in pyridine to yield the neutral adduct In(NRR')(3)(py) (R = R' = Ph; R = Me, R' = SiMe(3)). The volatile liquids In[N(t-Bu)(SiHMe(2))](3) and In[NMe(SiMe(3))](3)(py) react with p-Me(2)Npy to form the solid compounds In[N(t-Bu)(SiHMe(2))](3)(p-Me(2)Npy) and In[NMe(SiMe(3))](3)(p-Me(2)Npy), respectively. X-ray crystallographic studies show that In(NPh(2))(3)(py), In[N(t-Bu)(SiHMe(2))](3)(p-Me(2)Npy), and the ether adduct of In[NPh(SiMe(3))](3) contain nearly planar In(amide)(3) fragments. Crystallographic studies also show that the anion in the salt [Li(THF)(4)][In(NPh(2))(3)Cl] is nearly tetrahedral and in [Li(p-Me(2)Npy)][In{NMe(SiMe(3))}(4)] the tetrahedral-like anion is bound to the Li cation via two amide nitrogens. The Li in the latter structure is also bonded to p-Me(2)Npy, resulting in a planar three-coordinate geometry for Li. Crystal data are the following. C(31)H(52)N(3)OSi(3)In at -50 degrees C: P2(1)/n (monoclinic), a = 11.003(2) Å, b = 18.678(3) Å, c = 17.618(3) Å, beta = 95.42(1) degrees, and Z = 4. C(41)H(35)N(4)In.C(7)H(8) at -50 degrees C: P&onemacr; (triclinic), a = 10.112(2) Å, b = 12.786(3) Å, c = 15.870(5) Å, alpha = 87.42(2) degrees, beta = 74.95(2) degrees, gamma = 78.15(2) degrees, and Z = 2. C(25)H(58)N(5)Si(3)In at -50 degrees C: P2(1)/c (monoclinic), a = 9.797(3) Å, b = 18.203(6) Å, c = 19.592(5) Å, beta = 100.27(2) degrees, and Z = 4. C(52)H(62)ClInLiN(3)O(4) at 23 degrees C: P2(1)/n (monoclinic), a = 16.076(2) Å, b = 17.185(2) Å, c = 18.447(3) Å, beta = 97.41(1) degrees, and Z = 4. C(23)H(58)InLiN(6)Si(4) at 23 degrees C: P&onemacr; (triclinic), a = 15.792(3) Å, b = 16.345(3) Å, c = 16.678(3) Å, alpha = 62.69(1) degrees, beta = 81.00(1) degrees, gamma = 86.94(1) degrees, and Z = 4.

Journal Article↗

The influence of lithium fluoride on in vitro biocompatibility and bioactivity of calcium aluminate-pMMA composite cement.

The objective of this study is to assess the influence of lithium fluoride on in vitro biocompatibility and bioactivity of calcium aluminate (CA)-polymethylmethacrylate (PMMA) composite cement exhibiting quick setting time ( < 15 min), low exothermic temperature (< 47 degrees C), and high compressive strength (> 100 MPa). The biocompatibility was measured by examining cytotoxicity tests such as the agar diffusion test with L929 cell line and the hemolysis test with fresh rabbit blood. To estimate the bioactivity of CA-PMMA composite cement, we determined hydroxyapatite (HAp) formation on the surface of composite cement in the simulated body (SBF) solution by using thin-film XRD, XPS, SEM, EPMA and ICP-AES. The results of biocompatibility tests indicated that all experimental compositions of this study had no cytotoxicity and no hemolysis so that there was no cytotoxicity with regard to non-reacted monomers (MMA and TEGDMA) and lithium fluoride. The results of bioactivity tests revealed that CA-PMMA composite cement without lithium fluoride did not form HAp on its surface after 60 days of soaking in the SBF. On the other hand, LiAl2(OH)7 . 2H2O and HAp were formed on the surface of CA-PMMA composite cement including 1.0% by weight of lithium fluoride after 7 and 15 days of soaking in the SBF, respectively. The 5 microm of LiAl2(OH)7 . 2H2O and HAp mixed layers were formed on the surface of specimen after 60 days of soaking in the SBF.

Acrylic Resins↗

Synthesis of N-methoxy-N-methyl-beta-enaminoketoesters: new synthetic precursors for the regioselective synthesis of heterocyclic compounds.

[Structure: see text] Weinreb amides react with the lithium or sodium acetylide of ethyl propynoate in a hitherto unexplored acyl substitution-conjugate addition sequence to furnish (E)-N-methoxy-N-methyl-beta-enaminoketoesters. This approach provides a diverse entry to densely functionalized heterocyclic compounds, including pyrazoles through regioselective cyclocondensations with hydrazines in a microwave-assisted reaction.

Journal Article↗

Complex-induced proximity effects: the effect of varying directing-group orientation on carbamate-directed lithiation reactions.

A series of selected bicyclic carbamates in which the range of accessible angles and distances between the carbonyl group and the proton removed in an alpha-lithiation reaction are structurally defined have been investigated. Oxazolidinones 7-10 undergo stereoselective lithiation-substitution reactions to provide cis-18-27 and cis-31-35 as the major diastereomers. Two series of competition experiments show that the conformationally restricted carbamates 7, 10, 11, and 15 undergo lithiation via complexes more efficiently than Boc amines 4-6. These results along with semiempirical calculations suggest that a small dihedral angle and a calculated distance of 2.78 A between the carbamate carbonyl oxygen and the proton to be removed are favorable for a carbamate-directed lithiation. A series of tin-lithium exchange experiments on cis- and trans-18 and (S)-39 indicate that the configurational stability of a carbamate-stabilized organolithium species may be enhanced by restrictive geometry.

Bridged Bicyclo Compounds↗

In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse.

Methyl-delta-8-tetrahydrocannabinol (methyl-delta-8-THC), methyl-delta-9-THC and abn-methyl-delta-8-THC were synthesized by condensation of orcinol and (1S)-cis-verbenol and were administered to male Charles River CD-1 mice. Extracted hepatic metabolites were isolated by chromatography on Sephadex LH-20 and examined by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta-8-THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta-8-THC-11-oic acid. abn-Methyl-delta-8-THC was metabolized in a different manner. The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C(11) to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds. Metabolism of methyl-delta-9-THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C(8) and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta-9-THC-11-oic acid.

Aluminum↗

Synthesis and lateral root-inducing activity of novel N-substituted-2-piperidones with a 1,4-benzodioxan ring.

Novel N-substituted-2-piperidones with a 1,4-benzodioxan ring were prepared and evaluated for their activity to induce lateral roots in lettuce seedlings. Compounds were obtained by aldol condensation of the lithium enolate of N-substituted-2-piperidones with 1,4-benzodioxan-6-carbaldehyde. Of the series compounds tested, N-cinnamyl-3-[1-(1,4-benzodioxan-6-yl)-1-hydroxymethyl]-2-piperidone (2e) had the highest activity. In seedlings treated with 10 ppm of 2e, all of the primary roots formed lateral roots. Only erythro-2e showed lateral root-inducing activity, while threo-2e was inactive.

Dioxanes↗

Cytotoxic effects of two gamma linoleic salts (lithium gammalinolenate or meglumine gammalinolenate) alone or associated with a nitrosourea: an experimental study on human glioblastoma cell lines.

Gamma linoleic acid (GLA) salts may exert a direct antiproliferative activity on tumor cells. The cytotoxicity is linked to the generation of conjugated dienes, peroxyl radicals and superoxide radicals. Lithium gammalinolenate (LiGLA) and meglumine gammalinolenate (MeGLA) have been recently developed for enhancing the water solubility of these compounds. MeGLA or LiGLA (10(-5) to 10(-4) mol/l) and fotemustine (Fote) (2 x 10(-6) to 2 x 10(-4) mol/l) were applied, alone or in combination, for up to 9 days to two human glioblastoma cell lines A172 and U373MG. Fote was applied first followed by LiGLA and/or MeGLA. Cytotoxicity was evaluated by the MTT test, and the effects of drug combinations were analyzed by the isobolographic representation according to the Chou and Talalay method (combination indexes). For both GLA salts, cytotoxicity was manifested after 4 days of cell exposure and with very sharp dose-response curves. Comparison of IC50 values indicated that MeGLA was more active than LiGLA. There was a constant reduction in IC50 values following an increase in exposure time for A172 cells: between 4 and 9 days of cell exposure, IC50 changed from 73 to 46 microM for LiGLA and from 49 to 31 microM for MeGLA (p<0.05). With U373MG cells, there was no influence of exposure duration on IC50 values. Combination index values indicated that association between Fote and GLA salts globally resulted in slightly antagonistic effects. These results may be useful for further development of GLA salts at the clinical level.

Antineoplastic Agents↗