Amide Type Research Articles

Incidence of chirality on the properties of mixtures containing an amide type anesthetic compound

Thermal analysis carried out on the two binary systems between lidocaine and d-camphor, on the one hand, and dl-camphor, on the other hand, has shown that both systems form eutectic mixtures which are liquid at room temperature. Since these three substances present anesthetic properties, the mixtures elaborated from them are suitable for topical anesthesia. The similar behavior of d- and dl-camphor, regarding melting and crystallographic properties, implies similar binary temperature–composition phase diagrams when they are mixed with lidocaine.

ChemInform Abstract: Selective Oxidative Debenzylation of Mono‐ and Oligosaccharides in the Presence of Azides.

AbstractThe selective oxidative debenzylation using the conditions shown in the scheme are compatible with protecting groups of the ester and amide type.

Chemical interactions between an active pharmaceutical ingredient and its counterion in a tromethamine salt under forced degradation conditions

In this study, the tromethamine salt of an active pharmaceutical ingredient containing both a carboxylic acid and ethyl ester functionality was subjected to forced degradation conditions. Based on HPLC-MS analysis, it was found that tromethamine formed both amide and ester type condensation products with the API, with amide formation predominating over ester formation. Addition of tromethamine at the carboxylic acid group of the API was favored over addition at the ethyl ester group. Tromethamine condensation products were observed only under the harshest stress conditions (80 degrees and 75% relative humidity), in which the salt physically changed from a crystalline form to a deliquesced state. Under stress conditions in which the crystalline structure of the salt remained intact, good stability was observed. Thus, the interaction between tromethamine and API occurred only in cases where the crystallinity of the salt was compromised.

Synthesis of Novel Amide Molecular Tweezers under Solvent-Free Conditions Using Microwave Irradiation

Twelve novel amide type molecular tweezer anion receptors based on phenyl-1, 4-dioxyacetic acid have been synthesised using microwave irradiation. Their structures were established by 1H NMR, IR, MS spectra and elemental analysis. Their binding properties were examined by UV-Vis spectra titration. The preliminary results indicate that these molecular tweezers show good recognition properties for Cl-, Br-, I-, CH3COO-.

Isothermal and Non-Isothermal Crystallization Behavior of Poly(<i>L-Lactic Acid</i>) with Nucleating Agents

The effects of Amide type nucleating agents SX , talc and nucleating agents SX combination with talc on crystallization behavior of poly (L-lactic acid）(PLLA) were analyzed by means of Differential scanning calorimetry (DSC)．The results of non-isothermal crystallization showed that SX is an efficient nucleating agent. The crystallization peak temperature and degree of crystallization of PLLA sample with 0.6 wt% SX are both higher than that of PLLA sample with 4 wt% Talc，which proved that the nucleating ability of SX is stronger．Nucleating agent SX and talc combination has obvious coordination effects, the sample of PLLA/0.2 wt % SX + 4 wt % talc has the minimal crystallization undercooling temperature, the highest crystallization peak temperature and crystallinity. Isothermal crystallization kinetics of PLA showed that when the four nucleating agents added in are all with the Avrami exponent n between 2.1-2.5, crystallization tended to be heterogeneous nucleation. When the nucleating agents added in are 0.6 wt%, the crystallization time is greatly decreased to 0.75min. Meanwhile, the PLLA crystallinity could be significantly increased by adding SX nucleating agents; besides, with the decrease of the isothermal crystallization temperature, the half crystallization time of the PLLA/0.6 wt% SX sample was decreased.

Two- to One-Dimensional: Radii-Dependent Self-Assembly Crystal Structures and Luminescent Properties of Lanthanide Coordination Polymers with an Amide Type Semirigid Bridging Ligand

Lanthanide coordination polymers {[Ln2L3(NO3)6]·nH2O}n [Ln = Pr (1), Nd (2), Sm (3), Eu (4), Gd (5), Tb (6), Dy (7), and Er (8), where n = 0 except for 1 with n = 4 and 2 with n = 7] have been assembled using lanthanide nitrates and an amide type semirigid bridging ligand, 1,3-bis{[(2′-benzylaminoformyl)phenoxyl]methylbenzene (L), as building blocks. The crystal structures of the complexes {[Pr2L3(NO3)6]n·4H2O}n (1), {[Nd2L3(NO3)6]·7H2O}n (2), [Sm2L3(NO3)6]n (3), [Eu2L3(NO3)6]n (4), [Tb2L3(NO3)6]n (6), and [Er2L3(NO3)6]n (8)} were determined by single-crystal X-ray diffraction. Interestedly, 1 and 2 demonstrate unusual lanthanide porous noninterpenetrated honeycomb-like (6,3) topology frameworks, while 3, 4, 6, and 8 exhibit novel one-dimensional linear coordination polymeric structures. Their structural variations are attributed to lanthanide contraction effects. The luminescent properties of Sm(III), Eu(III), Tb(III), and Dy(III) complexes are also investigated in detail. The lowest triplet state (T1) energy level of this ligand matches better to the lowest resonance energy levels of Tb(III) and Dy(III) than Eu(III) and Sm(III) ions.

Clonidine as adjuvant for oxybuprocaine, bupivacaine or dextrorphan has a significant peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats

The aim of the study was to evaluate co-administration of clonidine with oxybuprocaine (ester type), bupivacaine (amide type) or dextrorphan (non-ester or non-amide type) and to see whether it could have a peripheral action in enhancing local anesthesia on infiltrative cutaneous analgesia in rats. Cutaneous analgesia was evaluated by a block of the cutaneous trunci muscle reflex (CTMR) in response to local dorsal cutaneous noxious pinprick in rats. The analgesic effect of the addition of clonidine with oxybuprocaine, bupivacaine or dextrorphan by subcutaneous injection was evaluated. On an ED50 basis, the rank of drug potency was oxybuprocaine>bupivacaine>dextrorphan (P<0.01). Mixtures of clonidine (0.12μmol) with oxybuprocaine, bupivacaine or dextrorphan (ED50 or ED95) extended the duration of action and increased the potency on infiltrative cutaneous analgesia. Among these drugs, the addition of clonidine to bupivacaine (amide type) elicits the most effective cutaneous analgesia. Clonidine at the dose of 0.12 and 0.24μmol did not produce cutaneous analgesia. Oxybuprocaine showed more potent cutaneous analgesia than bupivacaine or dextrorphan in rats. Co-administration of oxybuprocaine, bupivacaine or dextrorphan with clonidine increased the potency and duration on infiltrative cutaneous analgesia. The addition of clonidine to bupivacaine (amide type) elicits more effective cutaneous analgesia than oxybuprocaine (ester type) or dextrorphan (non-ester or non-amide type).

Assembly, crystal structures and luminescent properties of the lanthanide nitrate coordination polymers with 1,5-bis{[(2′-(2-picolylaminoformyl))phenoxyl]methyl}naphthalene

A new amide type bridging ligand, 1,5-bis{[(2'-(2-picolylaminoformyl))phenoxy]methyl}naphthalene (L), and its complexes with lanthanide ions (Ln Sm, Eu, Gd, Tb, and Dy) have been designed and assembled. The crystal structures of {[EuL(NO3)(3)(CH3OH)](H2O)}(n) and [TbL(NO3)(3)(CH3OH)](n) display one-dimensional (1-D) zig-zag coordination polymeric chains. At the same time, the solid state luminescent properties of the Sm, Eu, Tb, and Dy complexes were investigated at room temperature. The complexes all exhibit characteristic luminescence emissions of the central metal ions under UV light excitation. The lowest triplet state energy level (T-1) of the ligand indicates that the triplet state energy level of the ligand matches better to the resonance level of Tb(III) ion than other lanthanide ions. (C) 2011 Elsevier B.V. All rights reserved.

Determination of Mercury (II) Ion on Aryl Amide-Type Podand-Modified Glassy Carbon Electrode

A new voltammetric sensor based on an aryl amide type podand, 1,8-bis(o-amidophenoxy)-3,6-dioxaoctane, (AAP) modified glassy carbon electrode, was described for the determination of trace level of mercury (II) ion by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). A well-defined anodic peak corresponding to the oxidation of mercury on proposed electrode was obtained at 0.2 V versus Ag/AgCl reference electrode. The effect of experimental parameters on differential voltammetric peak currents was investigated in acetate buffer solution of pH 7.0 containing 1 × 10−1 mol L−1NaCl. Mercury (II) ion was preconcentrated at the modified electrode by forming complex with AAP under proper conditions and then reduced on the surface of the electrode. Interferences of Cu2+, Pb2+, Fe3+, Cd2+, and Zn2+ions were also studied at two different concentration ratios with respect to mercury (II) ions. The modified electrode was applied to the determination of mercury (II) ions in seawater sample.

Crystal structures and luminescent properties of lanthanide nitrate coordination polymers with structurally related amide type bridging podands

A one-dimensional linear chain coordination polymer [ErL I(NO 3) 3(CH 3CO 2Et)] n (L I=1,2-bis{[(2'-furfurylaminoformyl)phenoxyl]methyl}benzene) and a one-dimensional zig-zag coordination polymer {[TbL II(NO 3) 3(H 2O)]·(H 2O)} n (L II=1,2-bis{[2'-(2-pyridylmethylaminoformyl)phenoxyl]methyl}benzene) were assembled by two structurally related bridging podands L I and L II which have uniform skeleton and different terminal groups. In {[TbL II(NO 3) 3(H 2O)]·(H 2O)} n , the neutral chains were linked by the hydrogen bonding interactions between the free and coordinated water molecules from two different directions to interpenetrate into a 3D supramolecular structure. At the same time, the luminescent properties of the solid Tb(III) nitrate complexes of these podands were investigated at room temperature. The lowest triplet state energy levels T 1 of the podands L I and L II indicate that the triplet state energy levels of the antennae are both above the lowest excited resonance level of 5D 4 of Tb 3+ ion. Thus the absorbed energy could be transferred from ligands to the central Tb 3+ ions. And the influence of the hydrogen bonding on the luminescence efficiencies of the coordination polymers was also discussed.

1258 Perineal Block with Prilocaine During Labour: Effect on Newborns

Background: Prilocaine is a local anaesthetic of the amide type. Compared to other local anaesthetics of this group it has less cardiovascular and neurological side effects. However, the use of Prilocaine during labour has been associated with the occurrence of methemoglobinemia in newborns. Furthermore newborns seem to be at a higher risk of developing methemoglobinemia due to a lower level of methemoglobin reductase and the fact that foetal haemoglobin is more easily oxidized.Aim of the study: 1. To compare methemoglobin percentages in, during labour, prilocaine exposed and non-exposed newborns. 2. To study the incidence of methemoglobinemia in newborns. Study design and Results: 19 women who received 10ml prilocaine 1% as perineal block and their newborns were compared with 45 women and their newborns that were not exposed to prilocaine during labour. Of all the 64 newborns included, none had a methemoglobin percentage higher than 3%. There were no statistically significant differences between the methemoglobin percentages in both groups.A retrospective study including 355 newborns of which 136 were exposed to prilocaine was also carried out. The results of the retrospective study support those found in the prospective study.Implications of the study: Although newborns are at a higher risk of developing methemoglobinemia, this seems an infrequent problem in this age group. Furthermore, our data suggests that methemoglobinemia in newborns is a rare complication of prilocaine use. The occurrence of methemoglobinemia must be, therefore, weighed against the occurrence of cardiovascular and neurological side-effects of other local anaesthetics for perineal block.

New Hydrophobic Vitamin B12 Derivatives via Ring-Opening Reactions of c-Lactone

A selective synthesis of new hydrophobic cobalamin derivatives bearing two different spacers has been accomplished via ring-opening reaction of c-lactone. The reaction of c-lactone with various amines afforded three types of amides (a, b, and c) depending on the reaction conditions. The structure of lactone b was determined by the X-ray analysis confirming the position of ring closure. It also reveals the presence of a hydrogen bond between the terminal hydroxy group and one of the axial cyanide ligands.

Polyvinylphosphonic acid copolymer hydrogels prepared with amide and ester type crosslinkers

AbstractCrosslinked hydrogels made of poly(vinylphosphonic acid‐co‐N,N′‐methylenebisacrylamide) (P(VPA‐co‐MBAA)) and poly(vinylphosphonic acid‐co‐ethyleneglycol diacrylate) (P(VPA‐co‐EGDA)) were prepared by using precipitation polymerization in water medium. A comparison research was made between the resultant hydrogels containing different loads of vinylphosphonic acid segments when N,N′‐methylenebisacrylamide (MBAA) or ethyleneglycol diacrylate (EGDA) were used as comonomers. Morphological observations indicated that the resultant copolymer appeared as a fine powder at low VPA loadings and strongly aggregated at the high loadings; especially, a copolymer containing 63 mol % of VPA segments in P(VPA‐co‐MBAA) was observed to have a flake‐shaped appearance in its aggregated morphology. The resultant copolymer powders were characterized using FTIR spectroscopy and titrimetric analysis. Also, monomer reactivity ratios, r1 and r2, of VPA and MBAA or EGDA were estimated as 0.06 and 0.98 for VPA and MBAA and 0.05 and 1.82 for VPA and EGDA, respectively. This suggested that a large distribution of MBAA and EGDA was present in the resultant copolymer powders. Their crosslinked PVPA structure presented hydrogel properties having high water uptakes and an absorption mechanism independent from pH of bulk solution. The evidence showed that high VPA loadings could strongly interacted through hydrogen bonds between neighbor VPA segments even in the presence of water. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

ChemInform Abstract: A Safety-Catch Type of Amide Protecting Groups.

ChemInform Abstract: A Safety-Catch Type of Amide Protecting Groups.

ChemInform Abstract: Tellurium Amides as a New Tellurating Agent

Abstract Two types of tellurium amides have been prepared by the treatment of ArTeI or TeCl4 with LiNR2 in THF, and their reaction with acetylenes gave vinyl tellurides and dialkynyl tellurides.

Novel chiral poly(ester-imide)s with different natural amino acids in the main chain as well as in the side chain: synthesis and characterization

Several novel chiral and potentially biodegradable poly(ester-imide)s (PEI)s bearing natural amino acids in the main chain as well as in the side chain were synthesized via direct polyesterification of N,N'-(pyromellitoyl)-bis-(L-tyrosine dimethyl ester) as a biodegradable optically active phenolic diol and synthesized diacids containing different amino acids and phthalimide group in the side chain. With the aim of tosyl chloride/pyridine/N,N-dimethylformamide (DMF) system as a condensing agent under conventional heating condition, the new optically active PEIs were obtained in good yield and moderate inherent viscosity up to 0.35 dL/g. The obtained polymers were characterized with FT-IR, 1H NMR, X-ray diffraction (XRD), elemental and thermogravimetric analysis (TGA) techniques. They are readily soluble in amide type solvents such as N,N-dimethylacetamide, DMF, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, and protic solvents such as sulfuric acid. TGA showed that the 10% weight loss temperature in argon atmosphere was around 350 °C, which indicates that the resulting PEIs have a good thermal stability. The presence of amino acid in the PEIs architecture, not only cause to be used as optically active materials but also makes them susceptible to be biocompatible and biodegradable compound.

Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine–serine protein kinase B-dependent mechanism

Bupivacaine is one of the amide type local anesthetics and is widely used for epidural anesthesia and blockade of nerves. Bupivacaine administration locally could result in neuron injury showing transient neurologic symptoms. Dexamethasone is a synthetic glucocorticoid and may exert cytoprotective properties against damage induced by some stimuli. In the present study, we evaluated the effects of dexamethasone on bupivacaine-induced toxicity in mouse neuroblastoma N2a cells. N2a cells were exposed to bupivacaine in the presence or absence of dexamethasone. After treatment, the cell viability, nuclear condensation, and lactate dehydrogenase levels were evaluated. Mitochondrial potential and Akt (threonine–serine protein kinase B) activation were also examined. In a separate experiment, we examined the effect of Akt inhibition by triciribine on cell viability following dexamethasone treatment. We also investigated whether dexamethasone could prevent lidocaine-induced neurotoxicity. Treatment of N2a cells with bupivacaine resulted in significant cell injury as evidenced by morphological changes, LDH leakage, and nuclear condensation. Pretreatment of the cells with dexamethasone significantly attenuated bupivacaine- and lidocaine-induced cell injury. Dexamethasone treatment prevented the decline of mitochondrial potential caused by bupivacaine and increased the levels of Akt phosphorylation. Importantly, pharmacological inhibition of Akt abolished the protective effect of dexamethasone against bupivacaine-induced cell injury. Our data suggest that pretreatment of neuroblastoma cells with dexamethasone exerts a protective effect on bupivacaine-induced neuronal cell injury. The mechanisms involve activating the Akt signaling pathway.

Preparation and solid-state characterization of bupivacaine hydrochloride cyclodextrin complexes aimed for buccal delivery

Binary products of bupivacaine hydrochloride (BVP HCl), an amide type local anesthetic, with parent β-cyclodextrin (β-CD) and its soluble β-cyclodextrin-epichlorohydrin polymer (EPI-β-CD) were prepared and evaluated as a first phase in the development of a novel mucoadhesive formulation aimed for buccal delivery of this drug. The solid products were obtained by physical mixing, ball milling in high-energy mills, co-evaporation and lyophilisation, in order to rationally select the most effective preparation technique. The solid products obtained were carefully characterised by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and environmental scanning electron microscopy (ESEM). The impact of the preparation techniques on the physicochemical properties of plain drug was also studied. Results of solid-state analysis revealed more intense interactions of BVP HCl with EPI-β-CD than with native β-CD, accompanied by stronger reduction of drug crystallinity in the samples, probably favoured by the amorphous nature of the polymeric carrier. While summarising the results of DSC and XRPD analyses, it seems that ball milling of drug/cyclodextrin binary mixtures was particularly efficient in inducing solid-state interaction between the components and it can be considered as the method of choice for preparation of complexes of BVP HCl with β-CD and EPI-β-CD. In vitro dissolution properties in artificial saliva of ball-milled BVP HCl and corresponding CD complexes were investigated by simulating the conditions present at the surface of the buccal mucosa. The obtained results confirmed that complexation of BVP HCl with β-CD and EPI-β-CD is a suitable tool for properly tailoring the dissolution properties of the drug and it can be favourably exploited for the development of an effective buccal drug delivery system.

Elucidation of Mercury Ion Binding Property of a New Aryl Amide Type Podand by Electrochemical and Fluorescence Measurements

A new aryl amide type podand (AAP), 1,8-bis(o-amidophenoxy)-3,6-dioxaoctane, was synthesized and its mercury ion binding property was elucidated by electrochemical and fluorescence measurements. The effects of supporting electrolyte, pH and scan rate on the electroreduction of AAP and on cyclic voltommogram of mercury ion were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). It was observed that the complex formation between AAP and mercury ion exhibited pH-dependent behavior in different electrolyte solutions. Elucidation of such properties makes the AAP intriguing candidates as a modifying agent in sensor application for determination of mercury ion in mixture of aqueous solution.

Apoptosis induction by different local anaesthetics in a neuroblastoma cell line

Local anaesthetics are known to induce apoptosis in clinically relevant concentrations. Hitherto, it is unknown what determines the apoptotic potency of local anaesthetics. Therefore, we compared apoptosis induction by local anaesthetics related to their physicochemical properties in human neuronal cells. Neuroblastoma cells (SHEP) were incubated with eight local anaesthetics, two of the ester and six of the amide types. At least, five concentrations of each local anaesthetic were evaluated. After incubation for 24 h, rates of cells in early apoptotic stages and overall cell death were evaluated by annexin V and 7-amino-actinomycin D double staining by flow cytometry. The concentrations that led to half-maximal neurotoxic effects (LD50) were calculated and compared for all local anaesthetics. All local anaesthetics were neurotoxic in a concentration-dependent manner. All drugs induced similar rates of early apoptotic cell formation at low concentrations, whereas at high concentrations, late apoptotic or necrotic cell death predominated. Comparison of LD50 values of the different local anaesthetics resulted in the following order of apoptotic potency from high to low toxicity: tetracaine>bupivacaine>prilocaine=mepivacaine=ropivacaine>lidocaine>procaine=articaine. The toxicity correlated with octanol/buffer coefficients and also with experimental potency of the local anaesthetic, but was unrelated to the structure (ester or amide type). All commonly used local anaesthetics induce neuronal apoptosis in clinically used concentrations. The neurotoxicity correlates with lipid solubility and thus with the conduction blocking potency of the local anaesthetic, but is independent of the chemical class (ester/amide).