Aminoethyl Group Research Articles

Steric hindrance in cationic and neutral rhodamine 6 G molecules adsorbed on Au nanoparticles

The adsorption of cationic and neutral R6G molecules on Au nanoparticles was elucidated by surface enhanced Raman scattering (SERS). The steric hindrance at hydroethyl amino (‐N(H)Et) groups in R6G was evidenced by the observation that R6G+ adsorb on as‐prepared gold nanoparticles (AuNPs) only with electrostatic forces, in contrast to the electrostatic and chemical adsorption of R123+ with dihydro amino (‐NH2) groups on as‐prepared AuNPs. Large steric hindrance at the amino groups in R6G yielded saturated coverage of 700 molecules/AuNP for R6G+ significantly fewer than 1000 molecules/AuNP for R123+. In addition, neutral R6G0 on AuNPs showed markedly enhanced peaks at 1200–1600 cm−1, which were not observed in Raman spectra of R6G0 in bulk solution, and also in SERS of R6G+ on AuNPs. These bands are attributed to vibrational modes of an outer phenyl ring and ethyl amino groups, which are vertical to a xanthene plane, on the basis of theoretical analysis of molecular vibrations. Thus, Raman scattering of these bands is enhanced under an inclined orientation of R6G0 molecules chemisorbed on AuNPs via lone pair electrons at amino groups. Copyright © 2013 John Wiley & Sons, Ltd.

Extended Hydrogen Bond Network Enabled Superbases

New superbases, those organic compounds whose basicities are greater than that of proton sponge, are suggested that involve extended hydrogen-bonding networks. Addition of aminoethyl and related groups to the 1,8-diaminonaphthalene framework provide second- and third-layer hydrogen bonding in the conjugate base. DFT computations predict these compounds to be 10-15 kcal mol(-1) more basic than the proton sponge.

3,6,8-Tribromo-7-ethylamino-4-methyl-2H-chromen-2-one

In the title mol­ecule, C12H10Br3NO2, the 2H-chromen ring is essentially planar (r.m.s. deviation = 0.022 Å) with the ethyl­amino group oriented at 13.9 (5)° with respect to the ring. The mol­ecular structure is stabilized by intra­molecular N—H⋯Br and C—H⋯Br interactions.

Biocatalytic Synthesis and Structure Elucidation of Cyclized Metabolites of the Deacetylase Inhibitor Panobinostat (LBH589)

Panobinostat (LBH589) is a novel pan-deacetylase inhibitor that is currently being evaluated in phase III clinical trials for treatment of Hodgkin's lymphoma and multiple myeloma. Under catalysis of recombinant human CYP3A4 and CYP2D6 coexpressed with human cytochrome P450 reductase in Escherichia coli JM109, five metabolites of panobinostat were produced via whole-cell biotransformation. The structures of the metabolites were elucidated with the spectroscopic methods mass spectrometry (MS) and NMR and revealed an oxidative cyclization of the ethyl-amino group to the methylindole moiety. The MS(2) spectrum of the cyclized metabolite showed a base peak, where the closed ring is reopened and that, taken as sole base for structure proposals, would have lead to wrong conclusions. The metabolites were substantially less potent deacetylase inhibitors than the parent compound.

Molecular weight and pH effects of aminoethyl modified chitosan on antibacterial activity in vitro

Aminoethyl modified chitosan derivatives (AEMCSs) with different molecular weight (Mw) were synthesized by grafting aminoethyl group on different molecular weight chitosans and chitooligosaccharide. FTIR, 1H NMR, 13C NMR, elemental analysis and potentiometric titration results showed that branched polyethylimine chitosan was synthesized. Clinical Laboratory Standard Institute (CLSI) protocols were used to determine MIC for Gram-negative strain of Escherichia coli under different pH. The antibacterial activity of the derivatives was significantly improved compared with original chitosans, with MIC values against E. coli varying from 4 to 64μg/mL depending on different Mw and pH. High molecular weight seems to be in favor of stronger antibacterial activity. At pH 7.4, derivatives with Mw above 27kDa exhibited equivalent antibacterial activity (16μg/mL), while oligosaccharide chitosan derivative with lower Mw (∼1.4kDa) showed decreased MIC of 64μg/mL. The effect of pH on antibacterial activity is more complicated. An optimal pH for HAEMCS was found around 6.5 to give MIC as low as 4μg/mL, while higher or lower pH compromised the activity. Cell integrity assay and SEM images showed evident cell disruption, indicating membrane disruption may be one possible mechanism for antibacterial activity.

Anti-mycobacterial activities of some cationic and anionic calix[4]arene derivatives

Various polycharged calix[4]arenes were assayed as anti-mycobacterial agents against Mycobacterium tuberculosis, H37Rv strain. The sulfonate, carboxylate and phosphonate anionic species displayed no activity. Cationic derivatives integrating four aminoethyl groups at the upper rim and two 6,6′-dimethyl-2,2′-bipyridyl- or 4,4′-dimethyl-2,2′-bithiazolyl subunits at the lower rim were also found inactive against M. tuberculosis, while the unsubstituded and the 5,5′-dimethyl-2,2′-bipyridyl–analogues exhibited MIC values of 3.2 and 0.8μM respectively. Introduction of guanidinoethyl groups at the upper rim resulted, except for the 6,6′-dimethyl-2,2′-bipyridyl-derivative, in high anti-mycobacterial activities for the unsubstituted, the 5,5′-dimethyl-2,2′-bipyridyl– and the 4,4′-dimethyl-2,2′-bithiazolyl analogues, with MIC values of 0.8, 0.8 and 1.6μM, respectively, similar to those of current commercial anti-tuberculosis agents. The five more active substances were also evaluated against the isoniazid-resistant strain MYC5165, resulting in highly interesting micromolar or sub-micromolar MIC and IC50, ca. 4–125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.

VUV Photoionization and Dissociation of Tyramine and Dopamine: the Joint Experimental and Theoretical Studies

Photon induced dissociation investigations of neutral tyramine and dopamine are carried out with synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. At low photon energy only molecular ions are measured by virtue of nearthreshold photoionization. While increasing photon energy to 11.7 eV or more, four distinct fragment ions are obtained for tyramine and dopamine, respectively. Besides, the ionization energies of tyramine and dopamine are determined to be 7.98±0.05 and 7.67±0.05 eV by measuring the photoionization efficiency curves of corresponding molecular ions. With help of density function theory calculations, the detailed fragmentation pathways are established as well. These two molecular cations have similar aminoethyl group elimination pathways, C7H8O2+· (m/z=124) and C7H8O+· (m/z=108) are supposed to be generated by the McLafferty rearrangement via γ-hydrogen (γ-H) shift inducing β-fission. And CH2NH2+ is proposed to derive from the direct fission of C7-C8 bond. Besides, the McLafferty rearrangement and the C7-C8 bond fission are validated to be dominant dissociation pathways for tyramine and dopamine cations.

Microsolvation of the histamine monocation in aqueous solution: the effect on structure, hydrogen bonding ability and vibrational spectrum

Computational methods were employed to investigate the nature of the microsolvation of the histamine monocation that corresponds to the aminoethyl protonated state of histamine under physiological conditions. The calculations were carried out at the M06-2X/6-311+G(d,p) and M06-2X/6-311++G(3df,3pd)//M06-2X/6-311+G(d,p) levels of theory in conjunction with the PCM solvent reaction field of Tomasi and co-workers. The results revealed that at least five explicit water molecules are required for the trans Nτ–H conformer to overcome the larger intrinsic stability of the gauche Nτ–H counterpart, the former being experimentally determined as the most dominant structure of histamine in water. The calculated N–H stretching frequencies, corresponding to the protonated aminoethyl group and to the ring amino moiety, together with the quantitative analysis of the strength of the solute–solvent hydrogen bonds, provide evidence that the –NH3+ fragment forms stronger hydrogen bonds with the neighboring solvent molecules than the ring NH group. This distinction could not be obtained by experiments alone. In this way computational results offer new insight and complement experiments on features highly relevant for the function of this biologically important molecule.

POLYASPARTAMIDES GRAFTED WITH 1-(3-AMINOPROPYL)IMIDAZOLE AS LESS TOXIC AND HIGHLY EFFICIENT GENE CARRIERS

通过氨基引发聚丁二酰亚胺(PSI)开环反应,制备了系列侧链含氨乙基和咪唑丙基的聚(L-天冬酰胺)共聚物( P1~P5 ).该系列聚合物不仅具有极低的细胞毒性,而且随侧链中咪唑取代基含量的增加,聚合物在pH 5~8范围内缓冲能力显著提高.通过凝胶电泳、粒径和电位分析等研究了聚合物与质粒DNA的相互作用.结果表明,所有聚合物均可以在较低N/P比有效结合DNA.在N/P比高于5时,形成粒径在100 nm以下、表面电荷为+20 mV左右的稳定复合物纳米粒子.聚合物介导荧光素酶基因(pGL-3)和增强型绿色荧光蛋白基因(pEGFP-C1)体外转染293T细胞和COS-7细胞的结果表明,侧链中引入咪唑取代基显著提高了聚合物的转染能力.通过优化侧链氨基/咪唑取代基比例,获得转染效率最高的聚合物 P4 . P4 介导pGL-3和pEGFP-C1在细胞中的表达与聚乙烯亚胺(PEI)相当、甚至是PEI的2~3倍.

Carbonic anhydrase I and II activation with mono- and dihalogenated histamine derivatives

Mono- and dihalogenated histamine derivatives incorporating fluorine, chlorine and bromine have been prepared together with the corresponding boc-protected compounds at the aminoethyl group. They have been investigated as activators of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The cytosolic human (h) isoforms hCA I and II were moderately activated by the boc-protected halogenated histamines and very effectively activated by the deprotected ones. Low nanomolar and subnanomolar hCA I and II activators have been detected for the first time, starting from histamine as lead which has an affinity of 2 μM against isoform I and of 125 μM against hCA II.

Hydrogen Bond Dynamics of Histamine Monocation in Aqueous Solution: Car–Parrinello Molecular Dynamics and Vibrational Spectroscopy Study

Hydration of histamine was examined by infrared spectroscopy and Car-Parrinello molecular dynamics simulation. Histamine is a neurotransmitter and inflammation mediator, which at physiological pH conditions is present mainly in monocationic form. Our focus was on the part of vibrational spectra that corresponds to histamine N-H stretching, since these degrees of freedom are essential for its interactions with either water molecules or transporters and receptors. Assignment of the experimental spectra revealed a broad feature between 3350 and 2300 cm(-1), being centered at 2950 cm(-1), which includes a mixed contribution from the ring N-H and the aminoethyl N-H stretching vibrations. Computational analysis was performed in two ways: first, by making Fourier transformation on the autocorrelation function of all four N-H bond distances recorded during CPMD run, and second, and most importantly, by incorporating quantum effects through applying an a posteriori quantization of all N-H stretching motions utilizing our snapshot analysis of the fluctuating proton potential. The one-dimensional vibrational Schrödinger equation was solved numerically for each snapshot, and the N-H stretching envelopes were calculated as a superposition of the 0→1 transitions. The agreement with the experiment was much better in the case of the second approach. Our calculations clearly demonstrated that the ring amino group absorbs at higher frequencies than the remaining three amino N-H protons of the protonated aminoethyl group, implying that the chemical bonding in the former group is stronger than in the three amino N-H bonds, thus forming weaker hydrogen bonding with the surrounding solvent molecules. In this way the results of the simulation complemented the experimental spectrum that cannot distinguish between the two sets of protons. The effects of deuteration were also considered. The resulting N-D absorption is narrower and red-shifted. The presented methodology is of general applicability to strongly correlated systems, and it is particularly tuned to provide computational support to vibrational spectroscopy. Perspectives are given for its future applications in computational studies of tunneling in enzyme reactive centers and for receptor activation.

N,N-Diethyl-4-[9-methoxy-6-(4-methoxyphenyl)-5-methyl-2-phenyl-2H-benzo[h]chromen-2-yl]aniline

In the title compound, C38H37NO3, the pyran ring has an envelope conformation with the quaternary Cq atom as the flap atom. The dihedral angle formed between the meth­oxy­phenyl group and the naphthalene ring system is 67.32 (6)°. The ethyl­amino groups lie to the same side of the plane through the phenyl ring and form dihedral angles of 84.6 (3) and 75.8 (2)° with it.

Structure-cardiovascular activity relationships in a group of new 8-alkylamino-1,3-dimethyl-7-(2-hydroxy-3-aminopropyl)-3,7-dihydro-1H-purine-2,6-diones

On the basis of our earlier studies in a group of 7,8-disubstituted derivatives of 1,3-dimetyl-3,7-dihydropurine-2,6-dione, a series of new 8-alkylamino-1,3-dimethyl-7-(2-hydroxy-3-aminopropyl)-3,7-dihydropurine-2,6-diones (8-15) were synthesized and tested for their electrocardiographic, antiarrhythmic and hypotensive activity and for α1- and α2-adrenoreceptor affinities. Among the new derivatives, compounds with the 7-[2-hydroxy-3-(4-phenylpiperazine)-propyl] substituent (9-11) displayed prophylactic antiarrhythmic activity in epinephrine-induced arrhythmia. Analogue 10 with the 8-(2-morpholin-4-yl)-ethylamino group was the most active (ED50=3.9mg/kg and TI=59.8), which may indicate that this substituent is preferably important for the antiarrhythmic effect. Only compound 11 with the 8-(2-diethylamino)-ethylamino group significantly decreased the systolic (20.4–28.1%) and diastolic (23.4–33.2%) pressure, but this effect lasted for only 1–5min. The pharmacologically active compounds 9–11 with the phenyl-piperazine moiety showed affinity for α1-receptors (Ki=0.143–0.383µM), but the other compounds were almost (12–15) or completely (8) inactive at this site. Compounds 9–11 and 13–15 displayed moderate to low affinity for α2-receptors (Ki=0.36–2.7µM).

Infrared spectra of the protonated neurotransmitter histamine: competition between imidazolium and ammonium isomers in the gas phase

The infrared (IR) spectrum of protonated histamine (histamineH(+)) was recorded in the 575-1900 cm(-1) fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum of mass-selected histamineH(+) ions was obtained in a Fourier transform ion cyclotron resonance mass spectrometer coupled to an electrospray ionization source and an IR free electron laser. A variety of isomers were identified and characterized by quantum chemical calculations at the B3LYP and MP2 levels of theory using the cc-pVDZ basis set. The low-energy isomers are derived from various favourable protonation sites--all of which are N atoms--and different orientations of the ethylamine side chain with respect to the heterocyclic imidazole ring. The measured IRMPD spectrum was monitored in the NH(3) loss channel and exhibits 14 bands in the investigated spectral range, which were assigned to vibrational transitions of the most stable isomer, denoted A. This imidazolium-type isomer A with protonation at the imidazole ring and gauche conformation of the ethylamine side chain is significantly stabilized by an intramolecular ionic Nπ-H(+)···Nα hydrogen bond to the ethylamino group. The slightly less stable ammonium-type isomer B with protonation at the ethylamino group is only a few kJ mol(-1) higher in energy and may also provide a minor contribution to the observed IRMPD spectrum. Isomer B is derived from A by simple proton transfer from imidazole to the ethylamino group along the intramolecular Nπ-H(+)···Nα hydrogen bond via a low barrier, which is calculated to be of the order of 5-15 kJ mol(-1). Significantly, the most stable structure of isolated histamineH(+) differs from that in the condensed phase by both the protonation site and the conformation of the side chain, emphasizing the important effects of solvation on the structure and function of this neurotransmitter. The effects of protonation on the geometric and electronic structure of histamine are evaluated by comparing the calculated properties of isomer A with those of the most stable structure of neutral histamine A(n).

Development of pH-responsive fluorescent false neurotransmitters.

We introduce pH-responsive fluorescent false neurotransmitters (pH-responsive FFNs) as novel probes that act as vesicular monoamine transporter (VMAT) substrates and ratiometric fluorescent pH sensors. The development of these agents was achieved by systematic molecular design that integrated several structural elements, including the aminoethyl group (VMAT recognition), halogenated hydroxy-coumarin core (ratiometric optical pH sensing in the desired pH range), and N- or C-alkylation (modulation of lipophilicity). Of 14 compounds that were synthesized, the probe Mini202 was selected based on the highest uptake in VMAT2-transfected HEK cells and desirable optical properties. Using Mini202, we measured the pH of catecholamine secretory vesicles in PC-12 cells (pH approximately 5.9) via two-photon fluorescence microscopy. Incubation with methamphetamine led to an increase in vesicular pH (pH approximately 6.4), consistent with a proposed mechanism of action of this psychostimulant, and eventually to redistribution of vesicular content (including Mini202) from vesicles to cytoplasm. Mini202 is sufficiently bright, photostable, and suitable for two-photon microscopy. This probe will enable fundamental neuroscience and neuroendocrine research as well as drug screening efforts.

Sustained release properties of crosslinked and substituted starches

AbstractHigh amylose corn, waxy corn, and potato starches were crosslinked (XL) to an optimal degree and then substituted with carboxymethyl (CM) and aminoethyl (AE) groups, and their drug release properties, swelling power, and potential interactions with drugs were investigated. Propranolol hydrochloride, sodium diclofenac and acetaminophen were used as model drugs. High amylose starch required a higher XL degree to achieve good sustained release properties, whereas waxy corn required the least XL. Drug release was more governed by the matrix characteristics than by drug properties, and XL‐CM high amylose corn starch displayed a nearly constant drug release for all three drugs tested. Swelling power correlated well with sustained release properties with the better matrices swelling to greater extents. There was a potential interaction between XL‐AE‐starches and diclofenac as indicated by differential scanning calorimetry. Starches from different sources require different types and degrees of modifications to achieve satisfactory sustained release. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Ring contraction of 1,3-bis(5-bromopentyl)alloxazine

The reaction of 1,3-bis(5-bromopentyl)alloxazine with ethylamine in propan-2-ol resulted in replacement of the terminal bromine atoms by ethylamino groups and was accompanied by contraction of the pyrimidine ring so that the products were 1,3-bis[5-(ethylamino)pentyl]alloxazine and 1,3-bis[5-(ethylamino)-pentyl]imidazo[4,5-b]quinoxalin-2-one.

Specific Extraction of Sialic-acid-containing Glycans and Glycopeptides Using Serotonin-bonded Silica

Serotonin-bonded silica was developed for specific extraction of sialic-acid-containing glycans and glycopeptides. Serotonin, coupled by reductive amination with aldehyde silica particles via its ethylamino group, has strong affinity to sialic acid in glycan chain termini. Sialylated glycans trapped on serotonin silica particles are released by washing with ammonium acetate solution, providing highly efficient specific trap and release glycoconjugates. With >100 micromol/g adsorption capacity, the particles are applicable to purify labeled glycans after derivatization with 2-aminopyridine to remove excess reagents. Serotonin silica efficiently enriches sialic-acid-containing glycopeptides from tryptic digests for LC/MS analysis of glycans' heterogeneity in glycoproteins.

PREPARATION AND SURFACE CHARACTERIZATION OF CALCIUM HYDROXYAPATITE GRAFTING OF PHOSPHOETHANOLAMINE

Calcium hydroxyapatite (Ca10(PO4)6(OH)2: Hap) particles grafting of O-phosphoethanolamine (NH2(CH2)2 OPO3H2: PEA) were prepared by a coprecipitation method with a mixture of Ca(OH)2, H3PO4 and PEA at different PEA/(PEA+H3PO4) molar ratios in aqueous media at 85 °C. The crystallinity and particle size of Hap were decreased with an increase of PEA/(PEA+H3PO4) ratio, revealing that the crystal and particle growth of Hap were inhibited by grafting of PEA. The surface aminoethyl groups were generated by substituting the surface PO43- of Hap with PEA ions, giving rise to the decrease of surface P-OH groups of Hap. The number of surface aminoethyl groups was increased with increasing the PEA/(PEA+H3PO4) ratio and was ranged from 0.08 to 0.56 molecules/nm2. The surface aminoethyl groups would act as the irreversible adsorption sites of CO2.

Potent transglutaminase inhibitors, aryl β-aminoethyl ketones

Aryl β-aminoethyl ketones were discovered as potent inhibitors of tissue transglutaminase. Heteroaryl-like thiophene groups and N-benzyl N- t-butyl aminoethyl group are critical to the strong inhibitory activity of aryl β-aminoethyl ketones.