Aminopropyl Derivatives Research Articles

Fibre optic oxygen sensor for long term use in jet fuel, featuring phosphorescent dye chemically bonded to functionalised silica

Five new compounds, termed “metallo-porphyrin silicas”, have been synthesised by the reaction of functionalised silicas with platinum (II) meso tetrakis (pentafluorophenyl) porphyrin. The reaction resulted in the elimination of hydrogen fluoride to create a covalent bond between a functional group of the silica and the para carbon atom of a pentafluorophenyl group. Four out of the five new compounds exhibited phosphorescence under irradiation with u.v. light at ~400 nm, and in all four cases the phosphorescence was quenched by molecular oxygen. Stern Volmer plots of the four phosphorescent compounds showed that the aminopropyl derivative gave the largest response at 400 nm over a concentration range of 0–20% oxygen. Further tests were undertaken on this compound that showed that the output was dependant not only on oxygen concentration but also temperature (−17 °C–40 °C). A prototype probe suitable for testing oxygen content in aviation fuels was developed using an optical fibre. It was possible to detect changes in oxygen concentration in jet fuel. The results demonstrate the potential of this approach to provide a low cost, low power resilient probe for the detection of oxygen in aviation fuel.

Interferometric detection of chloramphenicol via its immunochemical recognition at polymer-coated nano-corrugated surfaces

Three types of polymer-coated glass slides were prepared by acylation of their γ–aminopropyl derivatives with succinic anhydride or poly(p-nitrophenyl acylate) (PNPA) at various reaction times. The variations in duration of chemical adsorption of PNPA allowed control over nano-corrugation of the reactive surfaces employed for biosensing. The visually smooth and optically clear polymer-coated slides were used for immobilization of a conjugate of bovine serum albumin with chloramphenicol (CAP) and label-free measurement of concentration of this antibiotic. The sensor chips prepared in this way provided strong biosensing response due to fast biomolecular interactions and efficient competition of the target analyte during indirect immunoassay. The kinetics of formation and dissociation of immune complexes “conjugate-antibody” on the sensor chip surface was registered by the label-free methods of spectral-correlation and spectral-phase interferometry. The average thickness of immune complex adsorption layers was in the range of 5–12 nm. The highest value of kinetic association constant (kon = 5 × 104 M−1s−1) and the lowest equilibrium dissociation constant (Kdiss = 2 × 10-8 M−1) were achieved with the chips originated in the PNPA-coated slides, which were produced under short (2 min) polymer chemisorption and exhibited nano-corrugation almost unchanged with respect to the parent glass, according to the atomic-force microscopy. The detection limit for CAP detection was 80 pg/mL, and the dynamic range was 5 orders. The proposed methods for fabrication of sensor chips with nano-corrugated surface, the results of their characterization, as well as the developed assay can be employed for high-throughput recording of multiple molecular interactions by spectral interferometry and in a wide range of biosensing platforms for registration of biologically active compounds in medicine, veterinary, food control and ecological monitoring.

Synthesis and biological evaluation of a trisaccharide repeating unit derivative of Streptococcus pneumoniae 19A capsular polysaccharide.

Streptococcus pneumoniae (SP) is a common human pathogen associated with a broad spectrum of diseases and it is still a leading cause of mortality and morbidity worldwide, especially in children. Moreover, SP is increasingly associated with drug resistance. Vaccination against the pathogen may thus represent an important strategy to overcome its threats to human health. In this context, revealing the molecular determinants of SP immunoreactivity may be relevant for the development of novel molecules with therapeutic perspectives as vaccine components. Serogroup 19 comprises the immune-cross reactive types 19F, 19A, 19B and 19C and it accounts for a high percentage of invasive pneumococcal diseases, mainly caused by serotypes 19F and 19A. Herein, we report the synthesis and biological evaluation of an aminopropyl derivative of the trisaccharide repeating unit of SP 19A. We compare two different synthetic strategies, based on different disconnections between the three monosaccharides which make up the final trisaccharide, to define the best approach for the preparation of the trisaccharide. Synthetic accessibility to the trisaccharide repeating unit lays the basis for the development of more complex biopolymer as well as saccharide conjugates. We also evaluate the binding affinity of the trisaccharide for anti-19A and anti-19F sera and discuss the relationship between the chemical properties of the trisaccharide unit and biological activity.

Characterization of Protonated Model Disaccharides from Tandem Mass Spectrometry and Chemical Dynamics Simulations.

The fragmentation mechanisms of prototypical disaccharides have been studied herein by coupling tandem mass spectrometry (MS) with collisional chemical dynamics simulations. These calculations were performed by explicitly considering the collisions between the protonated sugar and the neutral target gas, which led to an ensemble of trajectories for each system, from which it was possible to obtain reaction products and mechanisms without pre-imposing them. The β-aminoethyl and aminopropyl derivatives of cellobiose, maltose, and gentiobiose were studied to observe differences in both the stereochemistry and the location of the glycosidic linkage. Chemical dynamics simulations of MS/MS and MS/MS/MS were used to suggest some primary and secondary fragmentation mechanisms for some experimentally observed product ions. These simulations provided some new insights into the fundamentals of the unimolecular dissociation of protonated sugars under collisional induced dissociation conditions.

Transporter Targeted Gatifloxacin Prodrugs: Synthesis, Permeability, and Topical Ocular Delivery

In this work, we aim to design and synthesize prodrugs of gatifloxacin targeting organic cation transporter (OCT), monocarboxylate transporter (MCT), and ATB (0, +) transporters and to identify a prodrug with enhanced delivery to the back of the eye. Dimethylamino-propyl, carboxy-propyl, and amino-propyl(2-methyl) derivatives of gatifloxacin (GFX), DMAP-GFX, CP-GFX, and APM-GFX, were designed and synthesized to target OCT, MCT, and ATB (0, +) transporters, respectively. An LC-MS method was developed to analyze drug and prodrug levels in various studies. Solubility and log D (pH 7.4) were measured for prodrugs and the parent drug. The permeability of the prodrugs was determined in the cornea, conjunctiva, and sclera-choroid-retinal pigment epitheluim (SCRPE) and compared with gatifloxacin using an Ussing chamber assembly. Permeability mechanisms were elucidated by determining the transport in the presence of transporter specific inhibitors. 1-Methyl-4-phenylpyridinium iodide (MPP+), nicotinic acid sodium salt, and α-methyl-DL-tryptophan were used to inhibit OCT, MCT, and ATB (0, +) transporters, respectively. A prodrug selected based on in vitro studies was administered as an eye drop to pigmented rabbits, and the delivery to various eye tissues including vitreous humor was compared with gatifloxacin dosing. DMAP-GFX exhibited 12.8-fold greater solubility than GFX. All prodrugs were more lipophilic, with the measured log D (pH 7.4) values ranging from 0.05 to 1.04, when compared to GFX (log D: -1.15). DMAP-GFX showed 1.4-, 1.8-, and 1.9-fold improvement in permeability across the cornea, conjunctiva, and SCRPE when compared to GFX. Moreover, it exhibited reduced permeability in the presence of MPP+ (competitive inhibitor of OCT), indicating OCT-mediated transport. CP-GFX showed 1.2-, 2.3-, and 2.5-fold improvement in permeability across the cornea, conjunctiva, and SCRPE, respectively. In the presence of nicotinic acid (competitive inhibitor of MCT), the permeability of CP-GFX was reduced across the conjunctiva. However, the cornea and SCRPE permeability of CP-GFX was not affected by nicotinic acid. APM-GFX did not show any improvement in permeability when compared to GFX across the cornea, conjunctiva, and SCRPE. Based on solubility and permeability, DMAP-GFX was selected for in vivo studies. DMAP-GFX showed 3.6- and 1.95-fold higher levels in vitreous humor and CRPE compared to that of GFX at 1 h after topical dosing. In vivo conversion of DMAP-GFX prodrug to GFX was quantified in tissues isolated at 1 h after dosing. The parent drug-to-prodrug ratio was 8, 70, 24, 21, 29, 13, 55, and 60% in the cornea, conjunctiva, iris-ciliary body, aqueous humor, sclera, CRPE, retina, and vitreous humor, respectively. In conclusion, DMAP-GFX prodrug enhanced solubility, log D, as well as OCT mediated delivery of gatifloxacin to the back of the eye.

Versatile routes to C-2- and C-6-functionalized glucose derivatives of iminodiacetic acid.

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-alpha-beta-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-alpha-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a-c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of alpha and beta anomers.

Synthesis of (5-azido-2-nitrobenzoyl)amido, (4-azido-2-nitrophenyl)amino, and (5-azido-2-nitro-3,4,6-trifluorophenyl)amino derivatives of 17α-methylamino-, 17α-ethylamino-, and 17α-propylamino-5α-dihydrotestosterone as reagents of different linker lengths for the photoaffinity labeling of sex hormone binding globulins and androgen receptors

The photoactivable aryl azide reagents, N-(5-azido-2-nitrobenzoyl)oxysuccinimide, 4-azido-1-fluoro-2-nitrobenzene, and 4-azido-1-nitro-2,4,5,6-tetrafluorobenzene have been condensed at the extremity of three 17α-aminomethyl, 17α-aminoethyl, and 17α-aminopropyl side-chains introduced on (17S)-spiro-(3,3-dimethoxy)-5α-androstan-17β,2′-oxirane either directly, by ammonolysis, in the first case, or by conversion to nitrile intermediates with cyano or cyanomethyl anions and subsequent reduction to amines with lithium aluminum hydride, in the two other cases. The 3,3-dimethoxy group of these photoreagents was cleaved by acidolysis to a 3-ketone, which was reduced with sodium borohydride to a 3β-alcohol. All of these compounds were characterized by 1H- and 13C-NMR as well as by 1H, 13C heteronuclear 2D NMR, which helped to resolve ambiguous assignments. Significant differences of substituent-induced effects on 13C NMR signals were observed according to the 17α-side-chain length, the structure of the terminal aryl azide groups, and the solvent, showing a different behavior of N-5-azido-2-nitrobenzoyl derivatives as compared with 4-azido-2-nitrophenylamino and 5-azido-2-nitro-3,4,6-trifluorophenylamino derivatives. The N-5-azido-2-nitrobenzoyl conjugates of the three 17α-aminomethyl, aminoethyl, and aminopropyl derivatives of 5α-dihydrotestosterone were tested as ligands for purified human sex hormone-binding globulin and for the cytosolic androgen receptor of rat ventral prostate by competition experiments with tritiated 5α-dihydrotestosterone. The increasing lengths of the aminomethyl, aminoethyl, and aminopropyl spacer arms of N-5-azido-2-nitrobenzoyl conjugates were found to correspond to decreasing relative binding affinities for sex hormone-binding globulin (0.76, 0.47, and 0.10, respectively, versus 1.00 for 5α-dihydrotestosterone) while only the longer aminoethyl and aminopropyl conjugates interacted significantly with the androgen receptors (0.05 and 0.10, respectively).

Tyramine-containing poly(4-nitrophenylacrylate) as iodinatable ligand carrier in biodistribution analysis.

Targeted label or drug delivery requires access to convenient carrier systems and methods for efficient ligand conjugation. The main purpose of this study is to design an iodinatable synthetic polymer, whose application in vivo in tumor-bearing mice is tested with several related carbohydrate ligands, namely ABH and Lewis blood group epitopes. Tyramine and aminopropyl derivatives of the synthetic oligosaccharides were attached to poly(4-nitrophenylacrylate). Following iodination, the biodistribution of the sugar-free and the substituted polymers was determined in tumor-bearing mice. Flow cytofluorimetric analysis assessed tumor cell binding of further ligand types to human tumor cells in vitro. Quantitative ligand incorporation was achieved under mild conditions. Whereas the ligand-free poly[N-(2-hydroxyethyl)acrylamide] (MW 30 kDa) showed preferential accumulation in kidney, neoglycopolymers were found in substantial amounts in liver, kidney or spleen. The nature of the carbohydrate structure quantitatively influenced the distribution pattern. Tumor cell binding of blood group determinants and three further ligand types revealed non-uniform intensity in labeling and percentage of positive cells even in comparison between lines with identical histogenetic origin. Carbohydrate-exposing poly[N-(2-hydroxyethyl)acrylamide] polymers with tyramine as an iodine acceptor distribute in mice with a profile which is quantitatively influenced by small structural variations of the ligand part. Further refinement of the ligand structure may increase the level of selectivity for organ and tumor accumulation.

Enzymatic aminopropylation of certain secondary amines.

Two unusual aminopropyl acceptors found in a survey of putrescine binding sites of mammalian spermidine synthase, N-methylputrescine (I) and 4-aminomethylpiperidine (II), were examined for their aminopropyl derivatives. Studies under in vitro incubation conditions suggested that the aminopropyl derivatives of the secondary amine of I and II, N4-methylspermidine (Is) and 1-N-(3-aminopropyl)-4-aminomethylpiperidine (IIs), and of the primary amine of I and II, N8-methylspermidine (Ip) and 4-[N-(3-aminopropyl)aminomethyl]piperidine (IIp), respectively, were biosynthesized by rat spermidine synthase. Studies on the cell culture system of cultured rat hepatoma (HTC) cells treated with alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, clearly showed the presence of Is and Ip when I was administered, and IIs and IIp when II was administered, with no detection of putrescine or spermidine. These results suggested that mammalian spermidine synthase can transfer the aminopropyl moiety of decarboxylated S-adenosylmethionine to certain secondary amines in living cells.

Direct resolution of optically active isomers on chiral packings containing ergoline skeletons: II. Enantioseparation of carboxylic acids

Structurally different carboxylic acids and dansyl derivatives of amino acids were examined on a chiral stationary phase for high-performance liquid chromatography. The packing was prepared by bonding to silica gel an aminopropyl derivative of the ergot alkaloid (+)-terguride. Optimization of the enantioseparations was attained through the study of the influence of the organic modifier content and the pH and ionic strength of the buffer in the eluent. Electrostatic and hydrophobic interactions between the ergot alkaloid and the analyte contribute to a large extent to the retention and chiral discrimination. The selector was shown to be effective for the resolution of dicarboxylic acids, 2-arylcarboxylic acids and amino acid derivatives.

Taxonomic significance of polyamine synthesis in Paracoccus.

Five Paracoccus species, P. denitrificans, P. alcaliphilus, P. aminophilus, P. aminovorans and P. kocurii, ubiquitously contained putrescine and spermidine as major polyamines. Spermine and cadaverine were detected sporadically in some strains as a minor component. All the strains of these species produced norspermidine from diaminopropane supplemented into the medium and some strains produced two aminopropyl derivatives of cadaverine, i.e., aminopropylcadaverine and aminopentylnorspermidine. The biosynthetic ability of these unusual polyamines serves as a chemotaxonomic marker in the genus Paracoccus. P. denitrificans IFO 13301 decarboxylated ε-N-methyllysine as well as lysine but neither ε-N-acetyllysine nor δ-hydroxylysine. The orgranism formed 2-hydroxyspermidine from the supplemented 2-hydroxyputrescine as well as 2-hydroxynorspermidine from 2-hydroxydiaminopropane but not N-acetyispermidine and N-methylspermidine from N-acetylputrescine and N-methylputrescine, respectively. A halophilic species, P. halodenitrificans, which contains spermidine as the major polyamine and has no norspermidine- and aminopropylcadaverine-synthetic potential, was suggested not to be a valid member of the genus Paracoccus.

Novel polyamines in insects and spiders

1. 1. Diaminopropane, putrescine, norspermidine, spesrmidine, norspermine and spermine were commonly found in the larval silk gland and head of Bombyx mori, Antheraea yamamai and Galleria mellonella. 2. 2. The cockroach Periplaneta americana contained thermospermine, caldopentamine, caldohexamine, homospermidine, aminopropylhomospermidine and aminobutylhomospermidine (homospermine) in addition to the common polyamines. This is the first report to show the occurrence of the homospermidine derivatives and a hexamine in insects. 3. 3. In addition to thermospermine, caldopentamine, agmatine, histamine, cadaverine and other usual polyamines, three cadaverine-derivatives, aminopropylcadaverine, bis(aminopropyl)cadaverine and aminopentylnorspermidine, were detected in the silk gland and head of the spiders, Nephila clavata and Araneus ventricosus. The occurrence of aminopropyl derivatives of of cadaverine has never been reported in animals.

Polyamine distribution and the potential to form novel polyamines in phytopathogenic agrobacteria

Abstract Polyamines were analyzed in 4 species of genus Agrobacterium . Not only putrescine, spermidine and spermine, but also homospermidine and thermospermine were found in A. tumefaciens, A. radiobacter, A. rubi and A. rhizogenes . Trace amounts of aminopropylhomospermidine were also observed. Norspermidine and norspermine were formed from diamonorpropane added to the medium. Aminopropylcadaverine and its aminopropyl derivative(s) (aminopentylnorspermidine and N , N ′-bis(3-aminopropyl) cadaverine) were produced from the supplemented cadaverine. A strain of A. rhizogenes normally contains only putrescine and homospermidine; no other diamines, triamines and tetraamines were synthesized.

Occurrence of aminopropylcadaverine and its aminopropyl derivatives aminopentylnorspermidine andN,N′ -bis(3-aminopropyl)cadaverine inHalococcus acetoinfaciens

Besides putrescine, cadaverine, spermidine, spermine and thermospermine, three novel polyamines were detected in a slightly halophilic eubacterium Halococcus acetoinfaciens (IAM 12094, ATCC 25861). These novel polyamines were found to be N-3-aminopropylcadaverine [NH2(CH2)3NH(CH2)5NH2] and its aminopropyl derivatives: aminopentylnorspermidine [NH2(CH2)3NH(CH2)3NH(CH2)5NH2] and N, N′ -bis(3-aminoprophyl)cadaverine [NH2(CH2)3 NH(CH2)5NH(CH2)3NH2]. Aminopropylcadaverine was also detected in two other species, Halococcus agglomeratus (IAM 12095, ATCC 25862) and Halococcus nondenitrificans (IAM 12096, ATCC 25863).

Occurrence of aminopropylcadaverine and its aminopropyl derivatives aminopentylnorspermidine and N, N′ -bis(3-aminopropyl)cadaverine in Halococcus acetoinfaciens

Occurrence of aminopropylcadaverine and its aminopropyl derivatives aminopentylnorspermidine and N, N′ -bis(3-aminopropyl)cadaverine in Halococcus acetoinfaciens

Polyamine starvation causes accumulation of cadaverine and its derivatives in a polyamine-dependent strain of Chinese-hamster ovary cells.

Starvation of the polyamine-dependent Chinese-hamster ovary cells for ornithine or ornithine-derived polyamines in serum-free culture resulted in the formation of cadaverine and its aminopropyl derivatives, N-(3-aminopropyl)cadaverine and NN'-bis(3-aminopropyl)cadaverine. The synthesis of these unusual amines was inhibited by treatment of the cells with DL-2-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase (EC 4.1.1.17). In the absence of ornithine (the normal substrate), ornithine decarboxylase thus appeared to catalyse the decarboxylation of lysine to cadaverine. Cell proliferation was markedly inhibited by ornithine deprivation of the cells, and further depressed by exposure of the cultures to difluoromethylornithine.

Structure of agmatine sulphate dihydrate: an extensive amine–sulphate–water hydrogen-bond network

CsHI4N4.H2SO4.2H 20 , M r = 264.3, orthorhombic, Pbca, a = 22.251 (16), b = 7.199 (5), c = 15.849 (11) A, Z = 8, D m = 1.390, D e = 1.383 (3) Mg m -s. The structure was solved by heavy- atom and Fourier methods and refined to R = 0.060 for 1311 counter reflections. The agmatine chain is essentially planar, packing in layers parallel to ac. An elaborate network of N-H...O and O-H...O hydrogen bonds interlinks the amine, water and sulphate groups. Introduction. Some of the amines produced from amino acids by bacteria have pharmacological activity in animals (Fruton & Simmonds, 1965). These oligoamines are low molecular weight, aliphatic, non- protein, nitrogenous bases and include the simple diamines putrescine and cadaverine, the aminopropyl derivatives spermidine and spermine, and the peculiar guanidine bases such as agmatine and octopine found in invertebrate tissues and microbes. Oligoamines stimu- late chain elongation in systems containing DNA- dependent RNA-polymerase in vitro and also have follicle-stimulating hormone-releasing-factor activity. Agmatine sulphate dihydrate (ASD) (Fig. 1) was crystallized from aqueous methanol. Preliminary cell parameters were obtained from Weissenberg photographs and accurate values by least-squares refinement (Main & Woolfson, 1963) of 17 diffrac- tometer settings each measured at +20. Intensities were measured on a Picker four-circle diffractometer with

Replacement of natural polyamines by cadaverine and its aminopropyl derivatives in Ehrlich ascites carcinoma cells

Ehrlich ascites carcinoma cells were cultured in the presence of difluoromethyl ornithine (DFMO) and micromolar concentrations of cadaverine for several months. This treatment resulted in a complete disappearance of putrescine and spermidine and reduced spermine content to traces of its normal content. The natural polyamines were replaced by cadaverine (about 40% of total polyamines), N-(3-aminopropyl)cadaverine (about 50%) and N,N′-bis(3-aminopropyl)cadaverine (about 5%). In comparison with untreated cells or cells grown in the presence of DFMO and putrescine, the “cadaverine cells” grew definitely slower, their protein synthesis was depressed while DNA and RNA syntheses proceeded at near normal rate. In spite of the high intracellular concentrations of cadaverine and its aminopropyl derivatives, the tumor cells grown in the presence of DFMO and cadaverine, behaved exactly like cells severly depleted of putrescine and spermidine. Though exposed to DFMO, ornithine decarboxylase activity was almost 10 times higher than that in untreated cells. S-Adenosyl-L-methionine decarboxylase activity was likewise strikingly elevated, and these cells transported methylglyoxal strikingly elevated, and these cells transported methylglyoxal bis(guanylhydrazone) (MGBG) at a rate that was more than 5 times faster than that in untreated cells. Furthermore, these cells exhibited arginase activity, which was less than one fifth of that found in untreated cells.