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Summary form only given. Leucoemeraldine nitrogen amine has been oxidised by air and pure oxygen, and studied by X-ray Photoelectron Spectroscopy (X.P.S.). We discovered that the higher concentration in pure oxygen does not accelerate the oxidation process. Therefore, the air moisture has a great role in this phenomenon. The dopant concentration of the protonated form decreases with exposition time, concurrently to the oxidation process. Moreover, in addition to the amine nitrogen peak in the N1s XPS structure (at 399.0 eV calibrated versus C1s at 284.4 eV) of the base form, two peaks appear respectively at - 1.0 eV and +0.9 eV versus amine binding energy and correspond to imine and tertiary cycled nitrogen. A mechanism reaction is proposed to justify this tertiary nitrogen.

Optimal amidation conditions between hyaluronic acid (HA) and a methotrexate (MTX)-derived amine that gave rise to a HA-MTX conjugate having a molecular weight of ~2000 kDa have been established based on a model experiment using a tryptophan-derived amine in aqueous THF. This method is robust and provides a conjugate with properties of primary importance for efficacy-MW and amine binding ratio—that satisfy the criteria for a HA-MTX conjugate to be a good candidate.

Deprotonation of the CH2-bridged bis-imidazolium salt [H2(BIM(tBu))]Br2 followed by reaction with CuBr afforded polymeric [(BIM(tBu))2(CuBr)2]n (3), where BIM(tBu) = bis(3-tert-butylimidazole-2-ylidene)methane. In the solid state, compound 3 is an organometallic polymer with an unusual (-L-Cu-(micro-Br)2-Cu-L-)n type of bonding. The reaction of 3 with nitrogen bases N-tert-butylimidazole or piperidine splits the polymer and afforded the corresponding mononuclear amine adducts [(BIM(tBu))2(CuBr)2(amine)] (6 and 7, respectively). Their molecular structures revealed a unique bonding pattern, which has no precedents in copper-NHC coordination chemistry. The amine binding energies in 6 or 7 of 0.7-7.7 kcal mol(-1), calculated by DFT methods, are consistent with an experimentally observed ligand exchange in solution, fast on the NMR time scale.

The role of hydrophobicity and electronic factors in regulating alcohol inhibition of cytochrome P-450-mediated aniline p-hydroxylation has been investigated by the formulation of quantitative structure-activity relationships. The activity of linear primary alcohols and unhindered linear secondary alcohols shows a linear dependence on log P, where P is the octanol-water partition coefficient. Hindered primary and secondary alcohols are less active than this relationship predicts. An equation describing the activity of both hindered and unhindered primary and secondary alcohols shows that alcohol inhibition of aniline hydroxylation is regulated by hydrophobicity and steric effects. No role for electronic factors can be discerned. Similarities are found between alcohol inhibition and the binding of alkyl amines to cytochrome P-450, suggesting that alcohols may bind to the amine binding site.

Reserpine, a competitive inhibitor of catecholamine transport into adrenal medullary chromaffin vesicles, consists of a trimethoxybenzoyl group esterified to an alkaloid ring system. Reserpine inhibits norepinephrine transport with a Ki of approximately 1 nM and binds to chromaffin-vesicle membranes with a KD of about the same value. Methyl reserpate and reserpinediol, derivatives that incorporate the alkaloid ring system, also competitively inhibit norepinephrine transport into chromaffin vesicles with Ki values of 38 +/- 10 nM and 440 +/- 240 nM, respectively. Similar concentrations inhibit [3H]reserpine binding to chromaffin-vesicle membranes. 3,4,5-Trimethoxybenzyl alcohol and 3,4,5-trimethoxybenzoic acid, derivatives of the other part of the reserpine molecule, do not inhibit either norepinephrine transport or [3H]reserpine binding at concentrations up to 100 microM. Moreover, trimethoxybenzyl alcohol does not potentiate the inhibitory action of methyl reserpate. Therefore, the amine binding site of the catecholamine transporter appears to bind the alkaloid ring system of reserpine rather than the trimethoxybenzoyl moiety. The more potent inhibitors are more hydrophobic compounds, suggesting that the reserpine binding site is hydrophobic.

The first-pass pulmonary extraction values of N-lsopropyl-123l-p-lodoamphetamine (123I-IMP) in pretreated dogs decreases from 90 to 62% as the amount of propranolol increases from 0 to 20 mg. The first-pass pulmonary extraction values of 123I-IMP in dogs with a simultaneous bolus injection of propranolol decreases from 90 to 62% as the amount of propranolol increases from 0 to 10 mg. The pulmonary extraction of 123I-IMP with a simultaneous bolus injection of ketamine and 123I-IMP decreases from 90 to 64% as the ketamine dose increases from 0 to 100 mg. These results suggest that the pulmonary uptake of 123I-IMP may be at least partially mediated by receptors. They also indicate that endothelial metabolic cell function may be a useful index of early lung pathology. Furthermore, studies of the degree of lung uptake may be a sensitive index of pathologic states in which alterations of amine binding sites have occurred.

The ionophore lasalocid A forms 1:1 complexes with phenethylamines (1-amino-1-phenylethane and 1-amino-2-phenylethane) and catecholamines (dopamine and norepinephrine) in nonpolar solution. We have undertaken high-resolution proton nuclear magnetic resonance studies to deduce structural and kinetic information on the ionophore-biogenic amine complexes in chloroform solution. The coupling constant, chemical shift, and relaxation time data demonstrate that the lasalocid backbone conformation and the primary amine binding sites in the complexes are similar to those determined earlier for the alkali and alkaline earth complexes of this ionophore in solution. The exchange of lasalocid between the free acid (HX) and the primary amine complexes (RNH 3 X) in chloroform solution have been evaluated from the temperature-dependent line shapes at superconducting fields. The kinetic parameters associated with the unimolecular dissociation [Formula: see text] and the bimolecular exchange [Formula: see text] reactions have been deduced from an analysis of the lifetime of the complex as a function of the reactant concentrations. The relative stability of the complex decreases in the order phenyl > n -pentyl for substituents on the carbon α to the amino group (1-amino-1-phenylethane and 2-aminoheptane) and phenyl > 3,4-dihydroxyphenyl for substituents on the carbon β to the amino group (1-amino-2-phenylethane and dopamine). These results suggest that nonpolar interactions between the biogenic amine side chain and the lasalocid molecule contribute to the stability of the complex in solution.

Synthetic routes to macrocycles derived from (S)-phenyl alanine and (S)-cysteine have been developed. The catalyzed coupling of the Grignard reagent of 1-chloro-1-phenylethane and vinyl bromide in the presence of these ligands proceeds usually in good yields and in enantiomeric excesses (e.e.) of up to 46%.

Summary After incubation in a medium containing 6,7-dihydroxytetrahydroisoquinoline, slices of pineal gland and iris from reserpinized rats showed regranulation of a large number of small and large dense core vesicles in sympathetic boutons. The binding of 6,7-dihydroxy-TIQ to small vesicles that normally bind norepinephrine supports the suggestion that this alkaloid may be capable of functioning as a ‘false transmitter’.

The process of β-hydroxylation of dopamine (DA) and the fate of the newly formed noradrenaline (NA) were studied in high-speed sedimentable particles from bovine splenic nerves, after resuspension in potassium phosphate. The NA formation was found to be a linear function of the DA concentration in the medium. However, only a fixed amount of the newly formed NA was retained in the particulate fraction; the remainder appeared in the supernatant. Addition of NA to the medium reduced NA formation from DA, but hardly affected binding of the newly formed NA, while severely depressing DA retention. On the other hand, DA was shown to have about the same affinity as NA for the amine uptake mechanism of the particles. Reserpine added to the medium inhibited the formation of NA from DA, as well as the binding of NA and of DA, to an extent dependent on the drug/DA concentration ratio. The inhibition of NA formation was much less pronounced than that of firm amine binding. Although the results suggest that the membranes of the particles are permeable to NA and to DA, they do not rule out a certain inhibitory effect of reserpine on amine passage across the membranes. Washing was found to release loosely bound amines or amine derivatives from the particles. Loose binding appeared to be blocked by reserpine. The results indicate that deamination proceeds in the high-speed sedimentable particles. Inhibition of monoamine oxidase did not affect the NA formation from DA.

The cyclic polyether, 18-crown-6, reacts with protonated amines in methanol to form complexes whose formation constants (log K) decrease in the order NH4+, RNH3+ greater than R2NH2+ greater than R3NH+. In the case of the organic amines, this stability order is identical to the earlier observed permeability sequence for protonated organic amines in glyceryl dioleate bilayers treated with valinomycin, nonactin, or gramicidin, and in bullfrog and rabbit gallbladder membranes. The decrease in log K values in the above series is primarily a result of decreased enthalpy change (deltaH) values, the entropy change (TdeltaS) term being essentially constant for the systems studied.

Rat heart slices were incubated with tritium-labeled norepinephrine (NE) or other related amines, exposed to amphetamine or electric field stimulation, and the tritium efflux measured. Pretreatment with reserpine plus the monoamine oxidase inhibitor, pheniprazine, greatly decreased NE efflux following field stimulation, but markedly enhanced amphetamine-induced NE efflux. Pretreatment with 6-hydroxydopamine abolished this effect of amphetamine. Treatment of slices with guanethidine,α-methylnorepinephrine or amantadine also abolished or greatly diminished the amphetamine effect, while phenoxybenzamine or tetrabenazine were without effect. Although amphetamine also released metaraminol, an amine shown to be granule bound even in reserpine-treated systems, amantadine did not, suggesting that amantadine releases amines specifically from an extragranular neuronal binding site. A comparison of release of various amines by field stimulation (a measure of granule amine) and amantadine (a measure of extragranular amine) indicated that the extragranular binding site prefers amines with a catechol group (NE and dopamine) to those without (octopamine, tyramine) and that the beta hydroxyl group is not a significant factor in binding. The extragranular binding site may normally serve as a link in the intraneuronal catecholamine transport system.

The binding of serotonin to bovine adrenal medulla gangliosides (BAMG), bovine brain gangliosides (BBG), and BBG-synthetic lecithin mixed micelles has been demonstrated by a rapid technique using fluorescence monitoring of dialysis rates. BAMG micelles bound 0.10 mM serotonin at about half the efficiency of BBG micelles having the same sialic acid concentration (0.50 mM) in water. In water, the effect of BBG micelles was essentially identical to that of mixed micelles containing the same quantity of BBG. Ca2+ (1.20 mM), however, cancelled the effect of the mixed micelles on serotonin dialysis and reduced the effect of BBG micelles to about one quarter of that observed in water. These and other observations are related to earlier studies and to neurochemical processes which may involve gangliosides.

The effects of nicotine on the uptake and cellular distribution of 14C-norepinephrine (14C-NE)and 14C-dopamine (14C-DA) were examined in slices prepared from rat brain striatum and hypothalamus. Nicotine inhibited the uptake of both 14C-labelled norepinephrine and dopamine only in hypothalamus slices. Under similar incubation conditions, washout experiments with striatum and hypothalamus slices indicated that nicotine decreased the amount of 14C-NE and 14C-DA present in the slow washout component of the hypothalamus but did not alter 14C-labelled contents in the striatum. Addition of 0.62 mM nicotine produced a sustained increase in 14C-NE efflux from brain slices; the presence of desipramine or the absence of either sodium or calcium ions in the washout solution did not alter this nicotine-induced increase. These findings support the hypothesis that the nicotine-induced release of norepinephrine in the hypothalamus occurs by a specific and direct action at cellular amine binding sites or stores.

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue.

Freshly isolated rat hepatocytes were found to contain a 3-fold higher level of putrescine than perfused liver. The bulk of this diamine was recovered in the acid-insoluble fraction of the cell. In order to determine the nature of the amine binding, the levels of gamma-glutamylamine derivatives were measured. The method used involves exhaustive proteolytic digestion of the acid-insoluble fraction of hepatocytes, followed by ion-exchange chromatography. For N1-(gamma-glutamyl)putrescine, a combined ion-exchange chromatographic and reverse-phase h.p.l.c. procedure was adopted. This allowed for the direct detection of less than 50 pmol of this derivative in enzymic hydrolysates. Several of the gamma-glutamylamines reported previously [Beninati, Piacentini, Argento-Ceru', Russo-Caia & Autuori (1985) Biochim. Biophys. Acta 841, 120-126] in the whole organ were found in the isolated liver cells. The elevated level of N1-(gamma-glutamyl)putrescine and the absence of bis-(gamma-glutamyl)spermine was noteworthy. The results suggest that, in rat hepatocytes, both polyamine-dependent post-translational modification of some proteins and cross-linking between proteins involving the glutamine and lysine residues occurs.

The biologically inactive fluorinated nitrosamines N-nitroso-bis(2,2,2-trifluoroethyl)amine (NDEA-F6) and N-nitroso-bis-(2,2,3,3,4,4,4-heptafluorobutyl)amine (NDBA-F14) were investigated for binding affinity to cytochrome P-450 and for ease of alkali-induced proton abstraction at the alpha-C atom, in comparison with biologically active analogues (N-nitroso-diethylamine, NDEA; N-nitroso-2,2,2-trifluoroethylethylamine, NDEA-F3; N-nitrosodibutylamine, NDBA; N-nitroso-4,4,4-trifluorobutylbutylamine, NDBA-F3; N-nitroso-bis(4,4,4-trifluorobutyl)amine, NDBA-F6). Binding to cytochrome P-450 was studied by spectroscopic measurements (optical difference spectra with microsomal fractions); base-catalyzed deuterium exchange of alpha-hydrogen atoms was followed by 1H n.m.r. measurements. Additionally the excretion of NDEA-F6 and NDBA-F14 in expired air, urine and faeces was studied after oral application to the rat. Compared with the biologically active nitrosamine analogues, NDEA-F6 and NDBA-F14 showed higher binding affinity to cytochrome P-450. N.m.r. spectroscopy showed that NDEA-F6, NDBA-F14 and NDEA-F3 (at the fluorinated alkyl chain) were rapidly deprotonated at the alpha-C-position in sodium perdeutero methylate, in contrast to the other analogues tested. In vivo, NDEA-F6 and NDBA-F14 were excreted unchanged, mainly via exhalation. The biological inactivity of NDEA-F6 and NDBA-F14, together with the observed blocking of their microsomal activation can be reconciled with the experimental findings which indicate that homolytic alpha-C-H bond fission is more likely to be involved in alpha-C-hydroxylation of dialkylnitrosamines, than alpha-proton abstraction.

The activity of a purified pea diamine oxidase (DAO) was compared to that of a pea seedling enzymatic extract (PPE). It has been shown that DAO is able to catalyze as PPE the binding of amine to proteins as well as protein cross-linking reactions, but only if diamines and Cu2+ ions are both available in the medium. We proposed a mechanism in two steps for this reaction: first, an enzymatic step which induces the formation of an aldehyde resulting from the enzymatic oxidation of the diamine by DAO and, second, a chemical step catalyzed by Cu2+ which corresponds to the addition of nucleophilic amino acid side chain with the carbonyl group of the aldehyde. This last chemical reaction may lead in a first stage to the amine binding or in a second stage to protein cross-linking. Keywords: Pea seedling diamine oxidase; amine binding; cross-linking; deamidation; Pisum sativum

A study was carried out to compare the binding affinities of 1-dodecanethiol and dodecylamine for small Pt nanoparticles. The results showed that the affinity of thiol for Pt nanoparticles increases with increasing particle size whereas the affinity of amine for Pt nanoparticles decreases. The divergence in binding affinities has resulted in differences in catalytic activities of thiol- and amine-protected Pt nanoparticles in the room temperature electro-oxidation of methanol (a fuel cell reaction). It was therefore possible for the larger Pt nanoparticles to be catalytically more active than the smaller Pt nanoparticles up to a certain critical size, before the surface area effects of nanoparticles become noticeable.

The amine-binding properties of sand fly salivary yellow-related proteins (YRPs) were described only in Lutzomyia longipalpis sand flies. Here, we experimentally confirmed the kratagonist function of YRPs in the genus Phlebotomus. We utilized microscale thermophoresis technique to determine the amine-binding properties of YRPs in saliva of Phlebotomus perniciosus and P. orientalis, the Old-World vectors of visceral leishmaniases causative agents. Expressed and purified YRPs from three different sand fly species were tested for their interactions with various biogenic amines, including serotonin, histamine and catecholamines. Using the L. longipalpis YRP LJM11 as a control, we have demonstrated the comparability of the microscale thermophoresis method with conventional isothermal titration calorimetry described previously. By homology in silico modeling, we predicted the surface charge and both amino acids and hydrogen bonds of the amine-binding motifs to influence the binding affinities between closely related YRPs. All YRPs tested bound at least two biogenic amines, while the affinities differ both among and within species. Low affinity was observed for histamine. The salivary recombinant proteins rSP03B (P. perniciosus) and rPorASP4 (P. orientalis) showed high-affinity binding of serotonin, suggesting their capability to facilitate inhibition of the blood vessel contraction and platelet aggregation.