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Aim: To evaluate the antimicrobial effects of photoexcited silver sulfadiazine nanoliposomes (AgSD-NLs) doped by curcumin (AgSD-NLs@Cur) on Acinetobacter baumannii. Materials & methods: Following characterization, the cytotoxic and hemolytic activities of AgSD-NLs@Cur were evaluated. The antimicrobial activities of AgSD-NLs@Cur-mediated antimicrobial photodynamic therapy (aPDT) were determined. Histopathological examination of the burn wound sites of infected mice treated with photoexcited AgSD-NLs@Cur was assessed. Results: No significant cytotoxic and hemolytic activities were observed. There was a decrease in the Acinetobacter baumannii count in planktonic and biofilm forms and the gene expression level using AgSD-NLs@Cur-aPDT (p < 0.05). Histopathological analysis indicated the epidermis developed markedly and the bacterial load decreased significantly after aPDT. Conclusion: Photoexcited AgSD-NLs@Cur has an antimicrobial potential against A. baumannii.

Background Non-invasive sonodynamic therapy (SDT) is a new treatment modality that uses low-intensity ultrasound to activate a non-toxic sensitizing chemical agent for cancer therapy in a site-directed manner. This study aimed to investigate the anti-cancer effects of ultrasound combined with nano emodin transfersome (NET) on head and neck squamous cell carcinoma (HNSCC) cell lines. Materials and methods A transfersome form of nano emodin as a novel sono-responsive nanomaterial was synthesized to enhance the accumulation and penetration of nanoparticles. iIn vitro experiments including hemolytic activity, cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis induction, DNA fragmentation, and mRNA expressions of caspase 3 and 9 were conducted to explore the anti-cancer effects of NET-SDT on FaDu and CAL-27 cell lines. Results Characterization tests showed the round and uniform morphology of NET with transfersome structure, resulting in a high drug-loading content and encapsulation efficiency. No significant hemolytic activity was observed (P > 0.05). Cytotoxicity gradually increased with increasing concentrations of NET, so that 10 × 10–4 g/L of NET plus 5 min ultrasound irradiation at a frequency of 1 MHz and ultrasonic intensity of 2 W/cm2 effectively killed 98.2 % and 97.3 % of FaDu and CAL-27 cell lines, respectively (P Conclusions Our data demonstrated that SDT with NET as a sonosensitizer can induce apoptosis and significantly decrease cell viability of HNSCC cell lines, which represents the role of NET-SDT as a potent anti-cancer modality.

Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown. We aimed to investigate the involvement of nitrergic and opioidergic systems in bone loss relative to the RANK/RANKL/OPG pathway, in bile duct-ligated (BDL) rats. Eighty BDL/sham-operated (SO) rats received injections of 3 mg/kg/day Nω-Nitro-L-arginine methyl ester ± naltrexone (10 mg/kg/day) or saline for 28 days. Plasma bone turnover markers, OPG, RANK, and RANKL along with mRNA expression levels of the latter three were assessed. Plasma bone turnover markers and OPG level increased, but RANKL decreased in the BDL group compared with their SO controls (both: P ≤ 0.05). Administration of naltrexone reduced bone turnover markers and OPG level while increased RANKL content in comparison to BDL rats (P ≤ 0.05). As compared to untreated BDL rats, nitric oxide inhibition showed no effect on bone turnover marker i.e. OPG, RANK, and RANKL levels. BDL significantly increased RANK mRNA, but had no significant effect on RANKL and OPG mRNA expression. The lack of association between plasma levels and quantitative gene expression of RANKL and OPG suggests an indirect function of these markers in BDL rats. Considering that opioid receptor blockage by naltrexone in BDL animals caused a significant decrease in OPG and an increase in RANKL plasma contents, it could be postulated that the opioidergic system may have a regulatory effect on these bone markers.

Aims Allergic rhinitis is a global cause of disability, characterized by airway inflammation. Sumatriptan is a 5-hydroxytryptamine 1B/1D (5HT1B/1D) agonist used as a treatment for migraine headaches. Activation of 5HT1B/1D receptors can inhibit the release of neuropeptides and inhibit the inflammation cascades. This study investigated the effect of sumatriptan on ovalbumin-induced allergic rhinitis model in mice and the role of nitric oxide. Methods Female Balb/c mice were sensitized by intraperitoneal ovalbumin and challenged by intranasal ovalbumin. Mice received sumatriptan in doses 3, 10, 30 μg/kg intraperitoneally, 30 min before the last ovalbumin challenge. Key findings Intraperitoneal injection of sumatriptan significantly decreased the nasal scratching, IL-4 and serum IgE levels of allergic mice, but it increased IFNγ levels. Histopathological analysis showed that the number of eosinophils was significantly elevated in nasal mucosa of ovalbumin-induced allergic mice, while sumatriptan treatment significantly reduced the number of eosinophils. GR-127935, a selective 5-HT1B/1D-receptor antagonist, reversed the anti-allergic effects of sumatriptan. Acute administration of l -NAME, a non-specific inhibitor of nitric oxide synthase, along with sumatriptan attenuated the anti-allergic effects of sumatriptan but chronic administration of l -NAME did not affect the influences of sumatriptan. Furthermore, sumatriptan decreased the inducible nitric oxide synthase (iNOS) protein expression in allergic mice, but it did not change the concentration of eNOS protein. Significance This study shows that sumatriptan administration is associated with anti-allergic effects which are through 5HT1B/1D receptors. Decrease in iNOS expression and changes in T-helper 1&2 cytokines levels may indicate the involvement of inducible NOS and inflammation.

Induction of premalignant lesions in animal models is of high value for research purposes. This study aimed to induce dysplasia in hamster mucosal pouch for investigation of dysplastic lesions using dimethylbenz(a)anthracene. The buccal pouch of 10 hamsters was painted with dimethylbenz(a)anthracene for 10 weeks every other day. At 5 and 10 weeks, they underwent histopathological analysis. Clinically, there was no change until week 7; after which mucosal thickening occurred. Hamsters scarified at 5 weeks and 10 weeks demonstrated mild and moderate dysplasia, respectively. dimethylbenz(a)anthracene is a useful tool for inducing dysplastic lesions in the buccal pouch mucosa of hamsters.

Phosphatidylserine nanocochleates (Nanocochs) are novel delivery systems that may play a prominent osteoprotective role with their cargo, vitamin D3 (Vit-D3), against osteoporosis. Therefore, this study was conducted to characterize a Nanococh containing vitamin D3 (Nanococh-D3) and investigate its potential role in improving GIO in a rat model. Roll-shaped Nanococh-D3 particles were obtained in a size range of 320 nm with a sustained release performance. Oral Nanococh-D3 significantly increased the bioavailability of Vit-D3, enhanced bone mechanical strength, and improved osteogenic biomarkers including B-ALP, osteocalcin, Ca, and OPG in GIO rats. This formulation markedly suppressed gene expression of RANK and RANKL in treated rats. Histomorphometric analysis showed significant repairs in bone tissues and TRAP staining indicated a significant decrease in osteoclasts using Nanococh-D3 in osteoporotic rats. Nanococh alone similar to Nanococh-D3 acted better than AL as a standard anti-osteoporotic drug in the improvement of bone strength. In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.

The present study aimed to investigate the effects of phosphatidylserine liposomes (PSLs) and phosphatidylserine liposomes containing alendronate (AL-PSLs) on the improvement of methylprednisolone (MP) induced osteoporosis in a rat model. AL-PSLs formulation was prepared, characterized, and evaluated in different pH media to simulate gastrointestinal condition. Osteoporosis was induced by 3 weeks oral administration of MP (10 mg/kg) and then treatment by PSLs, AL-PSLs, and alendronate (AL). Bone metabolic and biomechanical markers were measured in treated rat groups. Also, Tartrate-resistant acid phosphatase (TRAP) staining and histomorphometry were evaluated on bone tissues of treated rats. AL-PSLs were obtained in a size range of 155 nm and negatively surface charge with an entrapment efficiency of 42%. The AL leakage from AL-PSLs did not exhibit a significant difference in acidic or basic media in comparison with the neutral condition. The concentrations of calcium, osteocalcin, bone alkaline phosphatase, and osteoprotegerin (OPG) of serum were significantly increased in PSLs and AL-PSLs treated groups compared to the MP group. Also, PSLs and AL-PSLs significantly improved the thickness and volume of the cortical and trabecular bone mass in treated groups. In addition, TRAP staining indicated a significant decrease of osteoclast number in osteoporotic rats treated with AL-PSLs and PSLs. In this study, AL-PSLs and even PSLs alone made a potential bone mechanical strength in glucocorticoid-induced bone loss more than AL in rats. In conclusion, our findings suggest that PSLs consumption with or without an anti-osteoporotic drug might be an applicable choice in control of osteoporosis.

Alzheimer's disease (AD) is closely associated with neuroinflammation development in the brain. Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation. Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD. Alzheimer's disease model was induced by bilateral intracerebroventricular injection of streptozotocin (3 mg/kg) into rat brains using the stereotactic technique. MET-PSL, MET, and PSL alone were administered intraperitoneally to AD-induced animals and factors including learning and memory storage in addition to cytokine and tissue inflammatory changes were evaluated after a 22-day experiment period. The learning and memory parameters significantly (P 0.05) improved in AD-rats treated with MET-PSL. Moreover, MET-PSL administration significantly (P 0.05) decreased cytokine levels of IL1-β, TNF-α, and TGF-β in hippocampal tissues of rats with AD. Histological results indicated a considerable reduction in inflammatory and necrotic neural cells along with significantly (P 0.05) increased neurogenesis in MET-PSL treated rats. Furthermore, our results showed that MET-PSL formulation could potentially act better than the free form of MET and PSL alone in the recovery process of rats with AD. In general, our data suggest that combination therapy of metformin loaded phosphatidylserine liposomes may enhance the therapeutic performance in AD patients of a clinical study.

New phosphorous catanionic amphiphiles were easily prepared by an acid−base reaction between (α-hydroxyalkyl)-phosphinic or -phosphonic acid and cethyltrimethylammonium hydroxide. In this way, we obtained, in nearly quantitative yields, bicatenary phosphinates and bicatenary and tricatenary phosphonates. The aggregation properties of these new catanionic amphiphiles were investigated at low concentrations in water (ranging from 1 to 5 mM), focusing in particular on spontaneous formation of different aggregate morphologies (vesicles, ribbons, tubules). Light and electron microscopy was used to identify the aggregate morphology of the catanionic amphiphiles. Moreover, these catanionic amphiphiles were able to organize into ordered lyotropic mesophases in concentrated water solutions, visualized by optical polarizing microscopy. Finally, the phosphorous catanionic amphiphiles, without rigid cores, were unexpectedly found to show thermotropic liquid-crystalline behavior. The various thermotropic mesophases we...

New double-chain bis-(α-hydroxyalkyl)phosphinic acids 1 are synthesized from NaH 2 PO 2 .H 2 O and aliphatic aldehydes. Direct and quantitative one-pot synthesis of new 4-alkoxybenzaldehydes 2 is realized from 1-bromoalkanesand 4-hydroxybenzaldehyde. Addition of NaH 2 PO 2 .H 2 O to aldehydes 2 leads to the formation of the bis-adducts and also to the cleavage of the ether bond. New [α-hydroxy-(4-alkoxybenzyl)]phosphinic acids 3 are prepared by addition of aldehydes 2 to aqueous hypophosphorous acid.

A new series of (α-hydroxyalkyl)phosphinic acids 1 was prepared in good yields from long-chain aldehydes (C8−C18) and 50% aqueous hypophosphorous acid under sonication. Oxidation of these phosphinic acids by dimethyl sulfoxide in the presence of catalytic amounts of iodine afforded the corresponding (α-hydroxyalkyl)phosphonic acids 2. Critical micelle concentrations (cmc) of the amphiphilic monocaternary (α-hydroxyalkyl)phosphorus acid ammonium salts 1 and 2, determined by tensiometry and 31P NMR, showed a good correlation between the two methods and indicated their high surfactant properties. The phosphonate salts 2 with two dissociable groups had much higher cmc values than those of the corresponding phosphinate analogues 1. The ammonium salts of these phosphorus acids were able to form ordered lyotropic mesophases in concentrated water solutions, visualized by optical polarization microscopy. The nature of the observed mesophases (hexagonal or lamellar) depended on the concentration, the temperature, t...

The reactivity of red phosphorus towards aldehydes was investigated under basic and acidic media. It was demonstrated that the real phosphorylating agent involved in the reaction was phosphane (PH3) in basic media, and hypophosphorous acid (H3PO2) in acidic media. A convenient one-pot synthesis of (α-hydroxyalkyl)phosphinic acids from red phosphorus and aldehydes in basic media was realized under sonication. The same reaction under acidic media in the presence of hydriodic acid led to the corresponding phosphonic acids. The (α-hydroxyalkyl)phosphinic acids were readily prepared under sonication from hypophosphorous acid and aldehydes in the presence of catalytic amounts of hydrochloric acid. The mechanism of the addition reaction of PH3 to benzaldehyde was elucidated and shows the complexity of the reaction as a function of the experimental conditions.

In the diphosphirane series, the substitution of one aryl group (2,4,6-tri-tert-butyl‐phenyl) by a chlorine atom leading to the trans P‐chloro-diphosphirane via the cis isomer intermediate can be readily realized in chlorinated solvent under sonication or in the presence of gaseous hydrogen chloride in diethyl ether at room temperature.

The synthesis of ortho-substituted benzoic acid 3 from benzalphthalide 1 in the presence of ‘hydriodic acid—red phosphorus’ (HIaq/Pred) occurs via the formation of benzylphthalide 2 as reaction intermediate. Its preparation is optimized by use of the ‘supported reaction in dry media’ process (Silica/HIaq) under microwave irradiation for 8 min. The role of the red phosphorus in the reduction reaction is elucidated: it intervenes in a catalytic cycle by an oxido—reductive disproportionation with the liberated iodine, affording either hypophosphorous acid in aqueous media, or P2I4 in anhydrous media with concomitant regeneration of HI. Thus, the presence of Pred in the couple ‘HIaq/Pred’ allows recycling of the hydriodic acid and enhances its reducing efficiency.

The generation of phosphine PH 3 by alkaline hydrolysis of red phosphorus is realized. The subsequent alkylation of PH 3 by terminal alkenes and alkynes in basic media leading to the corresponding aliphatic and vinylic phosphine derivatives can occur by two-steps or one-pot reaction by a Michael-like reaction mechanism.

In order to evaluate the biological properties of new α-aminophosphonic acids 4a-g bearing a pyrrolic or thiophenic moiety, their synthesis via the corresponding esters 3a-g is carried out by two methods. The standard procedure leading to α-aminophosphonic esters 3 in good yields, requires heating of the neat reactants for several days. The sonochemical activation improves substantially the rate of formation of 3 and promotes the yields of the reaction. The rate enhancement for this homogeneous sonochemical reaction depends upon the temperature, the nature of the solvent, and the structure of the imine

The metallation reactions of the functionalized diphosphiranes 1a,b with the anionic metal transition complexes Na[(Cp)nM(CO)m] (M  Mo, W, or Co) afford σ- or π -diphosphaallyl complexes depending on the substituents of the intracyclic carbon atom. The same complexes are also obtained from their photochemical isomers, the 1,3-diphosphapropenes 2a,b. The complexes are thermally labile as shown by variable-temperature NMR spectroscopy. Upon heating, the σ-diphosphaallyl cobalt complex 3aC is irreversibly transformed into the π-complex 4aC. In contrast, with M  Fe and in toluene solution at reflux, reduced 1,3-diphosphapropenes 5a,b are obtained. Further, the gem-dihalogenated diphosphiranes 1c,d and their isomers 2c,d lead quantitatively to 1,3-diphosphaallene 6 under the same metallation conditions. The mechanism of the coordination reactions is discussed.

Sonication improves substantially the rate of formation of diphosphene 1 with respect to standard procedures. The cyclopropanation of 1 using sonochemical generation of methylene or halogeno-carbenes constitutes an interesting alternative in the diphosphirane synthesis. Furthermore, ultrasonic effects in a chlorinated solvent allow the first substitution of a diphosphirane without ring-opening.

The cis/trans stereochemistry of diphosphiranes 1a–g, 2a, and 2h is investigated by MNDO calculations in terms of substituent effects on intracyclic phosphorus and carbon atoms. This approach is co...

The generation of phosphine PH 3 by alkaline hydrolysis of red phosphorus is realized. The subsequent alkylation of PH 3 by terminal alkenes and alkynes in basic media leading to the corresponding aliphatic and vinylic phosphine derivatives can occur by two-steps or one-pot reaction by a Michael-like reaction mechanism.

The role of base catalysts (CsNaX zeolite, hydrotalcite, triethylamine and pyridine derivatives) upon the regioselectivity of the Pudovik reaction is studied. The unexpected synthesis of stable 1,2-dihydropyridine phosphonate derivatives via a one-pot addition reaction under mild conditions is described.

The cis/trans stereochemistry of diphosphiranes 1a–g, 2a, and 2h is investigated by MNDO calculations in terms of substituent effects on intracyclic phosphorus and carbon atoms. This approach is completed by calculations of dipole moments. These results are compared to experimental dipole moment measurements of the synthesized diphosphiranes 3a–f.

Sonication improves substantially the rate of formation of diphosphene 1 with respect to standard procedures. The cyclopropanation of 1 using sonochemical generation of methylene or halogeno-carbenes constitutes an interesting alternative in the diphosphirane synthesis. Furthermore, ultrasonic effects in a chlorinated solvent allow the first substitution of a diphosphirane without ring-opening.

The cycloaddition reactions on Phosphorus Chemistry1 has allowed a new development of the three membered ring organophosphorus compounds. Starting from functionulized diphosphiranes obtained by action of carbenes on diphosphenes, we have studied their ring opening reactions leading to carbon insertion into P-P bond.

A method for the determination of free sulfite In wine by flow injection analysis (FIA) is described. The method Involves liberation of sulfur dioxide from the wine at pH 2.2, with detection by decolorlzation of a malachite green solution. The method was collaboratively studied, and the results indicated an average reproducibility of 12% for white wine samples (average level 12.1 ppm S02) and 26% for red wine samples (average level 3.1 ppm). When the FIA method was compared to an aeration/oxidation method, the results Indicated a high degree of correlation between the 2 methods. The FIA method has been adopted by AOAC official first action.

A method for the determination of total sulfite in shrimp, potatoes, dried pineapple, and white wine by flow injection analysis (FIA) was collaboratively studied by 8 laboratories. In the method, the sample solution Is reacted with sodium hydroxide to liberate aldehyde-bound sulfite. The sample stream is acidified to produce S02 gas, which diffuses across a Teflon membrane in the gas diffusion cell into a flowing stream of malachite green. The degree of discoloration of the malachite green is proportional to the amount of sulfite in the sample solution. Red wine was included in the study but Interlaboratory precision for these samples was not satisfactory and correlation with Monier-Williams results was poor. The present method is not recommended for use with these samples. For shrimp, potatoes, dried pineapple, and white wine, average reproducibility (RSDR) of results was 25% for samples at 10 ppm S02 and 10% for samples at >50 ppm. Overall average reproducibility was 14%. Recoveries of sulfite added to samples averaged 80%. Comparison of FIA with the Monier-Williams method indicated comparable results by the 2 methods. The FIA method has been adopted official first action for determination of ≥5 ppm total sulfite in shrimp, potatoes, dried pineapple, and white wine.

Direct synthesis of free (alpha-hydroxyalkyl)phosphinic acid amphiphiles 1 can be readily realized by sonication of the heterogeneous mixture of 50% aqueous hypophosphorous acid and long-chain aldehydes in the presence of catalytic amounts of hydrochloric acid. Oxidation of these phosphinic acids by DMSO in the presence of catalytic amounts of iodine quantitatively leads to the corresponding phosphonic acids 3. IR spectra of the phosphinic acids 1 in the condensed phase and in solution reveal the presence of intra- and intermolecular associations. Dissociation constants of the phosphorus acids 1 and 3 determined by potentiometric and (31)P NMR titrations show a good correlation between the two methods. The phosphinic acid amphiphiles 1 are slightly stronger than the corresponding phosphonic acids 3. (alpha-Hydroxyalkyl)phosphonium chlorides are prepared in good yields from the phosphine PH(3) and long-chain aldehydes in acidic media.

Extremely high rates of squamous cell carcinoma of the esophagus (SCCE) are observed in Iran, reflecting unknown, genetic and/or epidemiological risk factors. Among genetic alterations in SCCE, TP53 mutations are the most frequent, vary among populations, and may provide clues on etiological mechanisms. We have analysed mutations in TP53 (exons 5-8) in 98 SCCE from Iran by temporal temperature gel electrophoresis and direct sequencing. We found 58 mutations in 49 patients (50%), with a high prevalence of C to T transitions at CpG dinucleotides (29.3%). The TP53 mutation pattern in Iran was significantly different from that observed in SCCEs from high incidence areas of China and Western Europe (P=0.007). Moreover, the prevalence of mutations at A : T base pairs (transitions and transversions) was higher in men than in women (38.7% vs 11.1%, P=0.033). COX-2 overexpression was detected in 69% of the cases evaluated (24/35), without significant association with TP53 mutation. Accumulation of nitrotyrosine, a marker of protein damage by excess levels of nitric oxide, was observed in tumor cells in six of 18 [corrected] cases analysed. These results are consistent with the hypothesis that several factors are involved in TP53 mutagenesis in Iran. These factors include a baseline of chronic inflammatory stress, which may have a multiplicative impact on the sensitivity of esophageal cells to exogenous factors of risk.

Both the fluorescence yield and the yield of singlet oxygen generated from the quenching of the triplet state of two water-soluble hybrid molecules ‘zinc porphyrin-ellipticine’, (1) and (2), are low compared to those of simple zinc porphyrin complexes; both these photochemical properties are dramatically enhanced by addition of calf thymus DNA to solutions of (1) or (2), as a result of the conformation change of these hybrid molecules upon interaction with double-stranded nucleic acids.

The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido or an ether function), the position of amino group between the two parts of hybrid molecules, the number of intercalator moieties (ellipticinium) covalently attached to the metalloporphyrin, and the nature of the central metal atom (Mn, Fe, Zn) on the biological activity of these hybrid molecules were studied. In addition, these molecules have a high affinity for double-stranded DNA (affinity constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x 10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210 in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the nature of central atom. Iron derivatives are less active than manganese analogues and the corresponding zinc derivatives are nearly inactive despite their same affinity for nucleic acids. These highly water-soluble hybrid molecules could be considered as efficient bleomycin models based on a cationic metalloporphyrin.

The cycloaddition reactions on Phosphorus Chemistry1 has allowed a new development of the three membered ring organophosphorus compounds. Starting from functionulized diphosphiranes obtained by action of carbenes on diphosphenes, we have studied their ring opening reactions leading to carbon insertion into P-P bond.

The functionalized diphosphiranes 1 a–c, in presence of Lewis acid, undergo two kinds of reaction:the ring opening leading to the phosphenium-phosphonium ion 2a–c obtained according to an electrocyclic reaction and the fragmentation giving phosphaalkene 3a–c and phosphonium ion 4. The deprotonation reaction of 2a–c in hexane leads to phosphino-phosphaalkenes 6a–c.

Besides the expected spiropentane-methylenecyclobutane rearrangement that yields 2, another reaction channel plays a role in the thermolysis of 1: the diradical formed (in both cases) by P-P bond cleavage reacts by attack on the aryl residues, expelling tBu, to form 3.

Phospholipids are the main components of biological membranes and the) spontaneously tend to self-assembly into liposomes. Synthetic double-chain so as bol amphiphiles allow the preparation of vesicles and can bc used as models of natural membranes and for preparing drug delivery systems. The formation of vesicles from single-chain perfluomalkylated phosphate or phosphoramidate amphiphiles war recently reported.1 We present the synthesis of new fluoroalkylatcd phosphinic acid amphiphiles bearing a P-C bond and an ionic polar head promoting self-organisation We have already described the synthesis of the phosphine derivatives by one-poireaction from red phosphorus via the in situ generation of PH3, and terminal alkenes and alkynes in basic media under sonication.2 We extend this reaction to perfluoroalkena under phase uansfert catalysis.

Pursuing our investigation into h e reactivity of red phosphorus. its hydrolysis derivatives (PH3, and H3,PO2).1,2 and P-H labile compounds? we report here a convenient method for the direct synthesis of free a-hydroxyalkyl phosphinic acid surfactants from aqueous hypophosphorous acid and the long-chain aldehydes or imincs under sonication.

The synthesis of hybrid “metalloporphyrin-ellipticine” molecules is reported. These molecules are based on 9-methoxyellipticine and [5-(4-hydroxyphenyl)-10,15,20-tris (4-tolyl)]porphyrin linked by a ten-bond chain, −(CH2)4-CO-NH-(CH2)3−, between the hydroxyl group of the porphyrin and the pyridine nitrogen of the pyrido-carbazole. These molecules have been metallated with manganese, iron or zinc salts.

Different aspects of the reactivity of the diphosphene are presented: reactivity of the lone pair and/or reactivity of the double bond.

The reaction of α-branched aldehydes with diethyl 1-carbomethoxyethyl phosphonate 1b in THF/nBuLi at low temperature leads stereoselectively to Z α-methyl α,β-unsaturated esters. From a linear aldehyde, the reaction is less stereoselective, while from α,β-unsaturated ones, the E isomers are predominantly formed in good yields. From diphenyl 1-carbomethoxyethyl phosphine oxide 2b, E α-methyl α,β-unsaturated esters are stereoselectively formed either in DMF/tBuOK or in phase transfer conditions, whatever the starting aldehyde is, also in good yields. This reagent can thus advantageously replace the corresponding P-ylid. In all cases, the reaction conditions are determined so that by-products formation is minimized.

The reactivity of models of enzymatic carboxylation reactions mediated by biotin coenzyme is presented; a possible role of the requiered ATP molecule for these reactions was investigated. Several models of biotin activated through phosphorylation - according to the O-phosphobiotin model - are described and their reactivity to wards carboxylating agents discussed. Models also exhibit phosphoryl transfer properties which may mimic known ATP synthesis from ADP, catalyzed by biotin carboxylases. Possible involvement of the same O-phosphobiotin structure is considered.

Diphosphiranes 3a - 3f are obtained by action of diazo derivatives and carbenes on the trans-diphosphene 1 . The structures are elucidated by spectroscopic methods. In all cases the cycloaddition reaction is stereoselective.

This paper deals with the synthesis of N α -(β-naphthylsulfonylaminoglycyl)-argininamide compounds and the results of a pharmacological study ( in vitro and in vivo ). No thrombin inhibition was obtained with N α -arylsulfonyl-aminoalkyl-(4-amidinophenyl)-alaninamide compounds in which the 4-amidinophenylalanyl residue was substituted by an arginyl residue.

The Wittig-Horner reaction from diethyl cyanomethyl phosphonate 1a and aldehydes is seldom highly stereoselective1. The use of diiscpropyl cyanomethyl phosphonate 1b has been recently proposed to improve the stereoselectivity of the reaction towards the E-α, β- unsatured nitriles 2E2.

From NMR data, phosphine oxides 4 show similarity to Pylids and give E trisubstituted olefins from saturated and unsaturated aldehydes.

The functionalized diphosphiranes 1 a–c, in presence of Lewis acid, undergo two kinds of reaction:the ring opening leading to the phosphenium-phosphonium ion 2a–c obtained according to an electrocyclic reaction and the fragmentation giving phosphaalkene 3a–c and phosphonium ion 4. The deprotonation reaction of 2a–c in hexane leads to phosphino-phosphaalkenes 6a–c.

Hybrid molecules ‘cationic metalloporphyrin–intercalators’ have been synthesized which have a high affinity for double-stranded DNA and are able to cleave it at low concentrations; compound (2), an efficient bleomycin model based on a cationic metalloporphyrin, is cytotoxic towards murine leukaemia cells L1210 in vitro; iron and zinc analogues of (2) are less active, despite having the same affinity for nucleic acids.

Diphosphiranes 3a - 3f are obtained by action of diazo derivatives and carbenes on the trans-diphosphene 1 . The structures are elucidated by spectroscopic methods. In all cases the cycloaddition reaction is stereoselective.