Primary Amine Moiety Research Articles

Simultaneous Detection of Monoethanolamine, Diethanolamine, and Triethanolamine by HPLC with a Chemiluminescence Reaction and Online Derivatization to Tertiary Amine

In this paper we propose a new postcolumn detection method for compounds having primary, secondary, and tertiary amine moieties. The primary and secondary amine are delivatized by a reaction with epichlorohydrin having an epoxy moiety in a reaction coil to yield a tertiary amine with subsequent chemiluminescence detection using [Ru(bpy)3]3+. The liner values of the calibration curves of monoethanolamine (MEA), diethanolamine (DEA) and triethanolamine (TEA) were 0.02 - 1.0 nmol (r2 = 0.9986), 0.02 - 0.5 nmol (r2 = 0.9993) and 0.1 - 1.0 nmol (r2 = 0.9482), respectively. Also, the detection limits (S/N = 3) of MEA, DEA and TEA were 30, 25 and 40 pmol, respectively. The amount of DEA and TEA in shaving cream (60 microg/20 microL) were found to be 0.3 nmol and 14 nmol, respectively, by the proposed method.

Mass spectrometric characterization of substituted 2-thiazolin-4-one derivatives.

Electron ionization mass spectrometry was used for the structural characterization of substituted 2-thiazolin-4-one derivatives in the gas phase. The compounds follow common fragmentation pathways, producing ions whose abundances are dependent on the chemical nature of the substituent at position 2. Collision-induced dissociation tandem mass spectrometric experiments, carried out on both molecular ions and fragment ions produced in the source, allowed the elucidation of gas-phase decompositions. The presence of tautomeric forms is suggested for some ionic species. Rapid identification of a primary or secondary amine moiety at position 2 of the thiazoline ring can be achieved by the detection of characteristic fragmentations occurring both in the ion source and under the collision-induced dissociation regime.

Synthesis and Characterization of Nitrato-Triamine-Metal(II) Complexes. Conglomerate Crystallization Part 55. Crystal Structure of [Ni(dien)(O2NO)(ONO2)] (I), {[Cu(dien)-(μ-ONO2)]NO3}∞ (II), [Zn(dien)(O2NO)(ONO2)] (III), [Ni(Medpt)(O2NO)(ONO2)] (IV) and [Cu(Medpt)(ONO2)2] (V)

In absolute ethanol and in the presence of triethylorthoformate, reactions of metal(II) nitrates with linear tridentate amines afforded metal complexes of the formula M(NNN)(NO3)2, where M = Ni2+, Cu2+ and Zn2+, and NNN = dien and Medpt. The compounds fall into three categories in accordance with their stereochemistry and mode of binding of the nitrato ligands. Compounds I, [Ni(dien)(O2NO)(ONO2)] and III, [Zn(dien)(O2NO)(ONO2)] are isomorphous and isostructural. They crystallize in the monoclinic space group P21/n with nearly identical cell constants. The stereochemistry of these two compounds is such that the terdentate dien ligand forms a fac MN3 moiety with the two oxygens of the bidentate nitrato ligand trans to the terminal NH2. These ligands form the base of the octahedral arrangement in which the sixth position, trans to the secondary nitrogen of the dien, is an oxygen of the monodentate nitrato ligand. Compound IV, [Ni(Medpt)(O2NO)(ONO2)] falls into the same category as I and III despite the fact that the two rings in the Ni-Medpt moiety are six-membered rings, unlike those in compounds I and III which are five-membered rings. Nevertheless, the nickel-amine arrangement is fac. The bidentate nitrato-oxygens are trans to the terminal NH2 of the amine ligand, and the oxygen of the monodentate nitrato ligand is trans to the tertiary amine-nitrogen. Such stereochemistry is prevalent for nickel and zinc compounds. Interestingly, compound IV crystallizes as a conglomerate (space group P212121). Compound II, {[Cu(dien)(μ-ONO2)]NO3}∞ belongs to the second category and has a polymeric structure. The repeating fragment in the polymeric chain is a Cu(dien)-O fragment with the monodentate nitrato ligand occupying an equatorial position of the base. A second oxygen of the equatorial nitrate becomes an axial ligand for an adjacent Cu-N3O fragment. In this way the substance propagates into an infinite chain. The repeating unit has an effective square pyramidal, five-coordinate, configuration. Finally, the compound crystallizes as a racemate. The second nitrate necessary for charge compensation of this copper(II) compound is ionic and its function is to hold the infinite chains of the lattice. The third category represented by compound V, [Cu(Medpt)(ONO2)2] contains two molecules in the asymmetric unit of the racemic lattice (monoclinic, space group P21/a). The structure of Cu-Medpt is unlike that of IV in that both species present in the asymmetric unit have the amine ligand in a mer configuration which together with a monodentate oxygen of a nitrato ligand form a base plane of a square pyramid. The fifth ligand of both Cu2+ ions is a second monodentate nitrato ligand. The stereochemical differences between the two Cu2+ ions are insignificant for the Cu-Medpt fragment, which share the same conformation and configuration. The major difference between the two species is the torsional angles defined by the Cu-O-N-O angles. The difference arises from variation in the hydrogens of the primary amine moieties selected by nitrato-oxygens to form intramolecular hydrogen bonds. Finally, there is a little variation in the equatorial Cu-ONO2 stereochemistry because of steric hindrance, imposed by the Medpt, preventing large torsional angles by these nitrato ligands. This is evident by comparing the two copper species shown in Finally, nitrate-to-Br ligand exchange was found to take place when KBr pellets are prepared for IR spectral measurements.

Regioselective synthesis of N-functionalized 12-membered azapyridinomacrocycles bearing trialkylcarboxylic acid side chains

Abstract Selective protection of primary amine moieties of diethylenetriamine by 2-nitrophenylsulfonyl chloride followed by alkylation of the central N atom generates functionalized disulfonamide building blocks. When reacted with 2,6-bis(bromomethyl)pyridine following the Richman–Atkins methodology, such compounds yield the corresponding pyridine-containing azamacrocycles. Smooth removal of the N-sulfonyl groups provides versatile azamacrocyclic intermediates with transannular secondary amine functions. Subsequent N-alkylation regioselectively leads to tri N-functionalized 12-membered azapyridinomacrocycles bearing a sequence of N-acetate and N-propionate side chains.

SYNTHESIS AND CHARACTERIZATION OF POLYAMINE-BASED BIOMIMETIC CATALYSTS AS ARTIFICIAL RIBONUCLEASE

Several polyamine derivatives (I–V) conjugated with or without an intercalative moiety were prepared as ribonuclease mimics. Although no DNA-cleaving activity was observed for all compounds tested, mimics I,III, and V bearing an intercalative moiety along with the primary amine and/or imidazole moieties exhibited potent RNA-cleaving activity at near physiological pH. The RNA-cleaving reactions of the compounds show characteristic bell-shaped pH dependency, and the optimal pH values for III and V were well correlated to the pK a values of their active sites, primary amine, and imidazole moieties.

A Highly Chemoselective Protection and Activation of Primary Amines in Polyamine

Functionalization of polyamines containing both primary and secondary amine moieties could be achieved with the use of 2-nitrobenzenesulfonyl chloride. In the presence of a secondary amine, the primary amine groups are selectively transformed into the corresponding N-sulfonyl derivatives.

Modified Polysulfone Membranes. IV. Gas Separation with Aminated Polysulfone Membranes.

Novel gas permeation membranes were prepared from polysulfones and amine-modified polysulfones. The introduction of the primary amine moiety into polysulfone membranes led to an increase in permselectivity toward CO2 in CO2/N2 separation and a significant increase in that toward O2 in O2/N2 separation.

Selective benzoylation of primary amines in the presence of secondary amines

Compounds containing both primary and secondary amine moieties in the same molecule were treated sequentially with two equivalents of n-butyllithium at room temperature, two equivalents of TMSCl, one equivalent of n-butyllithium and one equivalent of benzoyl chloride, to afford mono-benzoylated diamines. Under these conditions, the primary amine moiety was selectively benzoylated.

Characterization of a novel spermidine/spermine acetyltransferase, BltD, from Bacillus subtilis

Overexpression of the BltD gene in Bacillus subtilis causes acetylation of the polyamines spermidine and spermine. BltD is co-regulated with another gene, Blt, which encodes a multidrug export protein whose overexpression facilitates spermidine export [Woolridge, Vazquez-Laslop, Markham, Chevalier, Gerner and Neyfakh (1997) J. Biol. Chem. 272, 8864-8866]. Here we show that BltD acetylates both spermidine and spermine at primary propyl amine moieties, with spermine being the preferred substrate. In the presence of saturating concentrations of acetyl CoA, BltD rapidly acetylates spermine at both the N1 and N12 positions. The Km (app) values for spermine, spermidine and N1-acetylspermine are </=67, 200 and 1200 microM, respectively. Diamines ranging from 1, 3-diaminopropane to 1,12-diaminododecane, monoacetylputrescine and N8-acetylspermidine were not substrates for BltD. Putrescine (1, 4-diaminobutane) and N8-acetylspermidine were competitive inhibitors of spermidine acetylation by BltD, with Ki values of 0.25 and 5.76 mM, respectively. CoA competitively inhibited both spermidine and acetyl-CoA interactions with BltD. These data and other results indicate that the mechanism of spermidine and spermine acetylation by BltD is a random-order mechanism of bi-molecular kinetics.

In vitro cytotoxicity and DNA damage production in Chinese hamster ovary cells and topoisomerase II inhibition by 2-[2'-(dimethylamino)ethyl]-1, 2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with substitutions at the 6 and 7 positions (azonafides).

The mechanism of action of a group of anthracene-containing analogs of amonafide was studied in Chinese hamster ovary (CHO) cells. These agents differ structurally from amonafide by the replacement of the naphthalene chromophore with an anthracene chromophore, the lack of a primary amine moiety in the 5 position, and substitutions at the 6 and 7 positions on the anthracene nucleus. In this study, five analogs with potent growth inhibitory activity and with low cardiotoxicity were chosen. Cytotoxicity analyses with tetrazolium dye assays (MTT) in vitro and continuous drug exposure revealed IC50 values in CHO cells in the nanomolar range. Intracellular scanning laser confocal microscopy of these drug-treated CHO cells showed that all analogs are able to enter cell nuclei with varying nuclear/cytoplasmic distribution: the more potent dimethylaminoethyl substituted analogs, 47 and 104, were primarily localized in the nucleus. Three analogs, including the unsubstituted parent (1), and numbers 35 (6-amino substituted) and 53 (6-aminoethyl substituted) inhibited DNA and RNA synthesis when assayed immediately after a 1 h exposure. In contrast, analogs 47 and 104 required 24 h post-drug exposure for 1 h to inhibit DNA and RNA synthesis. Using alkaline elution techniques, each analog also produced DNA single- and double-stranded breaks, as well as DNA protein cross-links. Interestingly, the most cytotoxic analogs, 47 and 104, produced minimal DNA strand damage in CHO cells at their IC90 concentrations, whereas the three other compounds with lower growth inhibitory potency produced marked and roughly equivalent DNA damage at equitoxic concentrations. Gel shift analysis of SV40 DNA exposed to the compounds demonstrated that these agents do not directly induce DNA strand breaks. However, catalytic studies with purified human topoisomerase II (Topo II) and plasmid DNA demonstrated that these drugs inhibit this enzyme. These results suggest that the azonafides inhibit Topo II to cause protein-associated strand breaks and impaired DNA and RNA synthesis. However, other mechanisms may also be operant, especially with the more potent dimethylamino ethyl substituted analogs.

Enantiomeric separation of β‐amino alcohols with a primary or tertiary amine moiety by reversed phase liquid chromatography with a chiral mobile phase containing copper (II) and (R)‐mandelic acid

Enantiomeric separation of β‐amino alcohols with a primary or tertiary amine moiety by reversed phase liquid chromatography with a chiral mobile phase containing copper (II) and (<i>R</i>)‐mandelic acid

A Bridgehead Enone Approach to Huperzine a

Abstract The preparation of a bicyclic amino ketone for the synthesis of huperzine has been achieved in only six steps. The key step is the introduction of the primary amine moiety via a bridgehead enone.

Use of 7,7,8,8-tetracyanoquinodimethane for spectrophotometric determination of certain local anaesthetics and procainamide hydrochloride

A simple and rapid spectrophotometric procedure has been developed for the determination of four local anaesthetics containing a free primary amine moiety and of procainamide hydrochloride as the drug substances and in dosage forms. The method is based on the reaction of the drug with 7,7,8,8-tetracyanoquinodimethane in alkaline solution to produce yellow products. The chromogen was measured at 473 nm. The effects of several variables on colour development were established. Job's plots of absorbance versus molar ratio of drug to reagent indicated a 1:1 ratio for all the drugs studied. Results of the analysis of drug substances and their dosage forms by the proposed method are in good agreement with those obtained by the USP XX method.

Fluorescent-labeled oligonucleotide probes: detection of hybrid formation in solution by fluorescence polarization spectroscopy

Fluorescein-labeled oligonucleotides as DNA-probes were synthesized and used to monitor hybrid formation, namely to detect DNA or oligonucleotide sequence in solution. The introduction of fluorescein to oligonucleotides was carried out by oxidation of a hydrogen phosphonate linkage with ethylenediamine or hexamethylenediamine as a tether and by a subsequent labeling of the primary amine moiety by FITC. Fluorescence anisotropy, r, was adopted as an index to monitor the behavior of F-probe in solution. An increase in the anisotropy was observed upon an increase in the chain-length of F-probe. When F-Probe formed a hybrid with its complementary oligonucleotide in solution, the r value increased compared to that of F-Probe itself. These observations clearly indicate that measurements of r in solution will readily lead to the monitoring of the presence of a hybrid in solution. Consequently, it is promising to detect a certain nucleic acid sequence in solution using fluorescent-labeled oligonucleotides.

Photochemical derivatization of agarose: Synthesis of an affinity agarose using a photoaffinity ligand specific for the peripheral-type benzodiazepine receptor

PK 14105, a photoaffinity ligand specific for the peripheral-type benzodiazepine receptor (PBZR), was photochemically coupled to ω-aminobutyl agarose (ABAg) to yield PK 14105 agarose (PKAg). 19F and 1H NMR spectroscopy were consistent with the proposed site of coupling at the 2′-fluorine of PK 14105 by the primary amine moiety of ABAg. Quantitation of the affinity gel using two different colorimetric assays for primary amines suggests approximately 50% of the available primary amine groups of ABAg were bound by PK 14105. The estimated concentration of PK 14105 bound to ABAg was 2.3 μmol/ml of settled gel (2.3 m m effective ligand concentration). PKAg specifically binds the bovine PBZR solubilized by digitonin. The affinity of PKAg for the soluble PBZR was estimated by varying the concentration of PKAg. PBZR binding to PKAg was saturable and the apparent affinity of PKAg for the bovine receptor was estimated from the saturation data. APKAg affinity column bound 85% of the solubilized PBZR from rat adrenals partially purified by anion exchange chromatography. These results indicate PKAg is a receptor-specific affinity media which may be useful in the purification of the native PBZR from various species.

Formation of Isoindole Derivatives of Sulfidopeptide Leukotrienes by Reaction with O-Phthalaldehyde and Separation by Reverse Phase High Performance Liquid Chromatography

Abstract A method is described for the formation of fluorescent conjugates of the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) by reaction of the primary amine moiety of these metabolites with o-phthalaldehyde. Separation of the fluorescent derivatives was achieved by reverse-phase high performance liquid chromatography in less than 30 minutes using a convex gradient of methanol-50 mM Na Acetate-5% Tetrahydrofuran pH 5.5. Detection limits realized under the conditions described were 0.35 ng, 3.8 ng and 3.7 ng for LTC4, LTD4, and LTE4, respectively. This represents an Increased sensitivity over detection of these metabolites by ultra-violet spectroscopy. The leukotriene-OPA derivatives are fully stable for 50 minutes at 23°C and for at least 4 hours at 0°C. The method is applied to the detection of LTC4 generated by zymosan stimulated murine peritoneal macrophages.

ChemInform Abstract: Synthesis and Biochemical Evaluation of Analogues of Aminoglutethimide Based on Phenylpyrrolidine-2,5-dione.

Das Aminophenylpyrrolidin-2,5-dion (V) wird als Strukturanaloges des Aminoglutethimid (VI) ausgehend von der Phenyl-butan- 1,2-dicarbonsäure (I) hergestellt und auf Inhibierung von Aromatase sowie des CSCC- Enzyms (CSCC: Cholesterol side chain cleavage) untersucht.

Synthesis and biochemical evaluation of analogues of aminoglutethimide based on phenylpyrrolidine-2,5-dione.

A series of (aminophenyl)pyrrolidine-2,5-diones has been prepared that bear structural similarities to aminoglutethimide (1, 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione). The inhibitory activity of these compounds was evaluated toward human placental aromatase and bovine adrenal cholesterol side chain cleavage (CSCC) enzyme assay systems. Selective, competitive inhibition of the aromatase enzyme system was demonstrated by 5 (3-(4-aminophenyl)-1-methyl-pyrrolidine-2,5-dione, Ki = 1.75 microM), 6 (3-(4-aminophenyl)-1,3-dimethylpyrrolidine-2,5-dione, Ki = 1.75 microM), 7 (3-(4-aminophenyl)-3-methylpyrrolidine-2,5-dione, Ki = 0.8 microM), and 8 (3-(4-aminophenyl)-3-ethylpyrrolidine-2,5-dione, Ki = 1.0 microM). Compound 15 (3-(4-aminophenyl)pyrrolidine-2,5-dione) proved unexpectedly difficult to prepare following standard methods and was only moderately inhibitory toward aromatase (IC50 = 20 microM). Compound 16 (3-(4-aminophenyl)-3-ethyl-1-methylpyrrolidine-2,5-dione) was weakly inhibitory toward testosterone aromatization and totally inactive toward androstenedione aromatization. These compounds were either weak or ineffective inhibitors of the CSCC enzyme systems, while 1 gave Ki values toward aromatase and CSCC enzymes of 0.68 and 14 microM, respectively. The unsubstituted phenylpyrrolidinediones were inactive in either system, and the 4-nitrophenyl derivatives exhibited weak, nonselective inhibition, indicating the importance of the primary amine moiety for potent inhibition of aromatase activity.

Dynamic surface properties due to amine migration and chemical reaction in primary amine/epoxide systems

We have studied the dynamic surface properties of four different primary amines in a low-molecular-weight epoxide resin by measuring dynamic spreading pressures. These spreading pressures directly manifest surface activity of the primary amines, which include three members of the dialkylaminopropylamine family (dimethyl, diethyl, and dibutyl), and the coupling agent γ-aminopropyltrimethoxysilane. Each of these systems shows a characteristic maximum in spreading pressure with time. Details of the transport processes (diffusion, chemical reaction, and adsorption) responsible for this time-dependence are illustrated in the context of a previously developed theory. The three dialkylaminopropylamines, for example, clearly show the effect of the reaction rate/diffusion rate ratio, or Damköhler number, on the dynamic spreading pressure. Likewise, by varying the bulk concentration of γ-aminopropyltrimethoxysilane, we have been able to demonstrate that saturation of the solution/vapor interface occurs for a bulk concentration of roughly 0.5 mass%. Further experiments using related silane compounds also suggest that the primary amine moiety is preferentially expelled from the solution phase, and is therefore responsible, in large part, for the observed surface activities.

Selective amidation of fatty methyl esters with N‐(2‐aminoethyl)‐ethanolamine under base catalysis

AbstractThe reaction of N‐(2‐aminoethyl)‐ethanolamine (AEEA) with saturated fatty methyl esters derived from coconut oil occurs under noncatalyzed conditions to yield principally N‐(2‐hydroxyethylamino)‐ethyl fatty amide,1, derived from the condensation of the primary amine moiety of AEEA with the methyl ester. In the presence of 0.25 wt % sodium methoxide at low reaction temperatures (&lt;90 C), 2 carboxamides are formed, the secondary monoamide,1 and also the tertiary monoamide, N‐(2‐aminoethyl)‐N‐(2‐hydroxyethyl) fatty amide,2. As this mixture of secondary and tertiary monoamides is heated to higher reaction temperatures (&gt;120 C), the concentration of secondary monoamide1 increases with a concomitant decrease in tertiary monoamide2. As the reaction time is increased at the elevated temperature, the tertiary monoamide continues to disappear. Increasing the base concentration to 2.5 wt % sodium methoxide, promotes selective formation of amide2 at low temperature. The results constitute evidence that at least 2 mechanisms are operating in fatty methyl ester amidations with AEEA and provide a classic example of thermodynamic vs kinetic control. Because amides1 and2 are intermediates to imidazoline amphoteric surfactants (powerful detergents, wetting agents, emulsifiers and so forth), knowledge of the reaction mechanisms in operation during the condensation of fatty methyl esters with AEEA will permit better understanding of the resultant products and the related processing conditions.