Acetylamino Group Research Articles

Dual roles of hydroxyl radicals and effects of competition on ozonation kinetics of two phenazone-type pollutants

Abstract Ozonation has been proved to be a promising approach for eliminating emerging pollutants in wastewater. In previous studies, emerging pollutants including diverse pharmaceuticals were found to exhibit significantly different ozonation reactivity. However, how the structural differences of emerging pollutants determine ozonation reactivity and mechanisms are still ambiguous. In this work, ozonation of dimethylaminophenazone (DMP) and acetylaminophenazone (AAA) with the same parent structure of phenazone but different substitution groups was investigated, in order to probe influencing mechanisms of structural differences on ozonation reactivity. Results show that DMP reacts with ozone and HO almost 2 and 1 order of magnitude faster than AAA, respectively. At pH 8, HO accelerates ozonation of DMP, but decreases ozonation of AAA. Competition simultaneously decreases degradation rate of the two phenazones, but effects on AAA are more significant than that on DMP. According to theoretical calculation results, differences in ozonation reactivity and mechanisms of the two phenazones can be mainly attributed to different substitution groups. The dimethylamino group in the structure of DMP increases the ozonation reactivity of phenazone by increasing reaction orbital energies and altering reaction sites, while the acetylamino group in the structure of AAA decreases the reaction orbital energy and therefore lowers the reactivity.

Synthesis of benzamide derivatives and their evaluation as antiprion agents

A new set of 5-(2-(pyrrolidin-1-yl)acetamido)-N-butyl-2-(substituted)benzamide and 5-(2-(piperidin-1-yl)acetamido)-N-butyl-2-(substituted) benzamide derivatives were synthesized in which as structural features the 2-(1-pyrrolidinyl)- or 2-(1-piperidyl)acetylamino group or a diphenylether moiety are associated to a benzamide scaffold. Their binding affinity for human PrPC and inhibition of its conversion into PrPSc were determined in vitro; moreover, the antiprion activity was assayed by inhibition of PrPSc accumulation in scrapie-infected mouse neuroblastoma cells (ScN2a) and scrapie mouse brain (SMB) cells. The results clearly indicate the benzamide derivatives as attractive lead compounds for the development of potential therapeutic agents against prion disease.

Chitin nanocrystals grafted with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and their effects on thermal behavior of PHBV.

Chemically modified chitin nanocrystals were synthesized by grafting poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) onto chitin backbone via chlorination. Acetyl amino group was maintained in the reaction. The chemical structure and morphology of PHBV grafted chitin nanocrystals were characterized by Fourier transform infrared, Transmission electron microscopy and X-ray photoelectron spectroscopy. Contact angle measurement showed that the lipophilicity of chitin was improved by the surface modification. The effects of original chitin and PHBV-graft-chitin nanocrystals on the crystallizing and melting behavior of PHBV were studied by differential scanning calorimeter (DSC). The results indicated that both unmodified and modified chitin nanocrystals suppressed crystallization of PHBV. The melt point of PHBV was increased after being mixed with nanofillers.

Narrow rim CMPO/adamantylcalix[4]arenes for the extraction of lanthanides and actinides

Six p-(1-adamantyl)calix[4]arenes 7, 8 with four differently attached diphenyl-carbamoylmethylphosphine oxide (CMPO) functions at the narrow rim were synthesized. This series was extended by adamantylcalix[4]arenes with two CMPO and two ester, acid or (diethylphosphono)acetylamino groups. Structures of new compounds were proved by NMR, mass-spectrometry and a single-crystal X-ray analysis for the intermediate di-phthalimide 10 3 . The extraction studies towards selected lanthanides and thorium showed that the ligands 7 surpassed the corresponding p-H, p- tert-butyl and p- tert-octyl analogues 3– 5 in lanthanide extraction while thorium was extracted with the same or lesser extent. For the lanthanide extraction D Ln( 7 4 )> D Ln( 7 3 )≈ D Ln( 7 2 ), which follows the order established earlier for ligands 3– 5. Among the tetra-CMPO derivatives of type 8, the ligand 8 3 / 4 was the best extractant for which the D Ln and D Th values were comparable with those for 7 4 .

Photosensitized [2 + 2] cycloaddition of N -acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer

Photocycloaddition between two adjacent bases in DNA produces a cyclobutane pyrimidine dimer (CPD), which is one of the major UV-induced DNA lesions, with either the cis-syn or trans-syn structure. In this study, we investigated the photosensitized intramolecular cycloaddition of partially-protected thymidylyl-(3′→5′)-N4-acetyl-2′-deoxy-5-methylcytidine, to clarify the effect of the base modification on the cycloaddition reaction. The reaction resulted in the stereoselective formation of the trans-syn CPD, followed by hydrolysis of the acetylamino group. The same result was obtained for the photocycloaddition of thymidylyl-(3′→5′)-N4-acetyl-2′-deoxycytidine, whereas both the cis-syn and trans-syn CPDs were formed from thymidylyl-(3′→5′)-thymidine. Kinetic analyses revealed that the activation energy of the acid-catalyzed hydrolysis is comparable to that reported for the thymine-cytosine CPD. These findings provided a new strategy for the synthesis of oligonucleotides containing the trans-syn CPD. Using the synthesized oligonucleotide, translesion synthesis by human DNA polymerase η was analyzed.

ChemInform Abstract: Synthesis and Pharmacological Evaluation of 4,4a,5,6-Tetrahydro-2H-thieno(2,3-h)cinnolin-3-ones Bioisosters of Antihypertensive and Antithrombotic Benzo(h)cinnolinones.

Abstract The 8-acetylamino-4,4a,5,6-tetrahydro-2H-thieno[2,3-h]cinnolin-3-one (2b) has been synthesized and tested for its pharmacological profile in comparison with the bioisoster 8-acetylamino-4,4a,5,6-tetrahydrobenzo(h)cinnolin-3(2H)one (1b), which we reported to be a potent antihypertensive and antithrombotic agent. The new compound retained antithrombotic properties which were higher than those of acetylsalycilic acid but without significant antihypertensive activity. Conformational analysis performed by molecular mechanic calculations suggests that the lack of activity could be due to a different orientation of the acetylamino group in the 2 compounds. In addition, the unsubstituted term 2a was found to be comparable to ASA as an antithrombotic agent.

Selenodiazole-fused diacetamidopyrimidine, a selective fluorescence sensor for aliphatic monocarboxylates

A designed sensor, selenodiazole-fused pyrimidine ring having two acetylamino groups at 2,4-positions has been synthesized for selective recognition of aliphatic monocarboxylate anions over a wide range of other anions. The recognition study has been carried out by UV–vis and fluorescence methods. A significant bathochromic shift of the fluorescence intensity of the receptor in the presence of carboxylate makes the receptor a discriminating sensor for aliphatic monocarboxylates.

Molecular structure, p K a, lipophilicity, solubility and absorption of biologically active aromatic and heterocyclic sulfonamides

The methods of theoretical chemistry have been used to elucidate molecular properties of clinically useful acetazolamide, dorzolamide and brinzolamide and two new aromatic sulfonamides in both neutral and deprotonated forms. The geometries and energies of these drugs have been computed using HF/6–31G(d), Becke3LYP/6–31G(d) and Becke3LYP/6–311+G(d,p) model chemistries. The equilibrium structure of the acetazolamide is stabilized via intramolecular interaction between non-bonded S···O atoms of the acetylamino group and the thiadiazole ring. In the case of the aromatic sulfonamides (4-sulfamoyl- N-(3-morpholinopropyl) benzamide (P10), and N-(morpholinopropyl)benzene-1,4-bis(sulfonamide) (P20)) the fully optimized most stable conformers possess characteristic L-shape structure stabilized via intramolecular hydrogen bonding system of the N–H···N type. Computed partition coefficients (XLOGP2 method) for drugs studied varied between –0.3 and –1.8. Neutral compounds are described as slightly lipophilic drugs. The calculated water solubility of dorzolamide and brinzolamide is comparably low. P10 and P20 are slightly lipophilic sulfonamides with moderate solubility. The calculated p K a values of –SO 2NH 2 moiety in the sulfonamides studied are in the range of 7.3–9.7 and are characterized as weak organic acids.

Quantum mechanical calculations of the cephalosporin nucleus

A computational study using several ab initio methods, HF, DFT and MP2 at different basis set levels (6-31G*, 6-31G**, 6-311G** and 6-311++G**) has been performed to determine the possible stable conformations attained by the cephalosporin nucleus. The calculations were carried out in three stages by studying the conformational analysis of the 3-cephem nucleus, the 3-cephem-4-carboxylic acid nucleus and the acetylamino group of the 7-acetylamino-3cephem-4-carboxylic acid. In the first two stages, the potential energy surfaces indicated two minima that correspond to the S1-up and C2-up conformations, with the S1-up being more stable. The energy required for the interconversion of the S1-up to the C2-up is around 7 kcal/mol, indicating the feasibility of interconversion between the two conformers. In the third stage, the acetylamino group attained two conformations with respect to the 3-cephem nucleus. All the geometric parameters obtained in this study were found to be in reasonably good agreement with available X-ray diffraction data, even upon using a simple basis set.

Stereoselective formation of a cyclobutane pyrimidine dimer by using N4-acetyl protection of the cytosine base

The cytosine base in DNA undergoes hydrolytic deamination at a considerable rate when UV radiation induces formation of a cyclobutane pyrimidine dimer (CPD) with an adjacent pyrimidine base. As a part of our study on the synthesis of CPD-containing oligonucleotides, we have prepared properly-protected thymidylyl-(3' 5')-N(4)-acetyl-2'-deoxycytidine, and the solution of this compound was UV-irradiated using acetophenone as a sensitizer. In this reaction, hydrolysis of the acetylamino group occurred, and a trans-syn cyclobutane thymine-uracil dimer with the syn-anti conformation around the glycosidic bonds was formed stereoselectively.

Novel azo dyes derived from phthalimide. Part 1: Synthesis and spectroscopic properties

A series of azo dyes has been synthesised based on N-alkylphthalimide diazo components featuring one of three different alkyl groups. An analogous set of dyes was prepared in which the N-alkylphthalimidylazo systems bore an o,o-dibromo-substitution pattern. In these cases, cyanodebromination was performed to give the corresponding dicyano analogues. All the synthesised intermediates and dyes were characterised by mass spectrometry, proton nuclear magnetic resonance spectroscopy and elemental analysis. The absorption maxima of the dyes in dimethylformamide (N,N-dimethyl ∼) were observed to be in the range 435–608 nm and found to be consistent with results seen in previous studies of conventional monoazo disperse dyes. Replacement of both halogens in the dibromo-substituted dyes with cyano groups led to large bathochromic shifts (128–141 nm) in absorption maxima. Bathochromism was also observed when acetylamino groups were present on the coupler ring ortho to the azo link. However, variation of the N-alkyl function on the imido ring from n-butyl to sec-butyl and iso-propyl had little effect on absorption maxima, values being similar to that reported for the parent N-unsubstituted analogue.

Poly(amido amine)s as Gene Delivery Vectors: Effects of Quaternary Nicotinamide Moieties in the Side Chains

To evaluate the effect of quaternary nicotinamide pendant groups on gene delivery properties, a series of poly(amido amine) (co)polymers were synthesized by Michael addition polymerization of N, N'-cystaminebisacrylamide with variable ratios of 1-(4-aminobutyl)-3-carbamoylpyridinium (Nic-BuNH(2)), and tert-butyl-4-aminobutyl carbamate (BocNH-BuNH(2)), yielding poly(amido amine)s (NicX-NHBoc) with X=0, 10, 30, and 50 % of quaternary nicotinamide groups in the polymer side chains. Deprotection of the pendant Boc-NH groups afforded an analogous series of polymers (NicX-NH(2)) with higher charge density (due to the presence of protonated primary amino groups in the side chains) and subsequent acetylation yielded a series of polymers (NicX-NHAc) of lower hydrophobicity than the Boc-protected polymers. The polymers with the Boc-protected or the acetylated amino groups showed high buffer capacity in the range pH 5.1-7.4, which is a property that can contribute to endosomal escape of polyplexes. The presence of quaternary nicotinamide groups has distinct beneficial effects on the gene vector properties of these polymers. The polymers containing >or=30 % of quaternary nicotinamide groups in their side chains condense DNA into small, nanosized particles (<or=200 nm) with positive surface charge (>or=+15 mV). Fluorescence experiments using ethidium bromide as a competitor showed that the quaternary nicotinamide groups intercalate with DNA, contributing to a more intimate polymer-DNA binding and shielding. Polyplexes of nicotinamide-functionalized poly(amido amine)s NicX-NHBoc and NicX-NHAc, formed at 12/1 polymerDNA mass ratio, efficiently transfect COS-7 cells with efficacies up to four times higher than that of PEI (Exgen 500), and with essentially absence of cytotoxicity. NicX-NH(2) polymers, possessing protonated primary amino groups in their side chains, have a higher cytotoxicity profile under these conditions, but at lower 3/1 polymer-DNA mass ratio also these polymers are capable of efficient transfection, while retaining full cell viability.

One‐pot synthesis of N2‐aminoprotected 6‐substituted and cycloalka[d] 4‐trifluoromethyl‐2‐acetylaminopyrimidines

Abstractmagnified imageThe one‐pot synthesis of a novel series of amino‐protected 6‐alkyl‐, 6‐aryl‐, 6‐heteroaryl‐ and 5,6‐fused‐cycloalkane 4‐trifluoromethyl‐2‐acetylaminopyrimidines, where alkyl = Me; aryl = Ph, 4‐CH3Ph, 4‐FPh, 4‐ClPh, 4‐BrPh, 4‐OCH3Ph, 4‐NO2Ph, 4,4′‐biphenyl, 1‐naphthyl; heteroaryl = 2‐thienyl, 2‐furyl and cycloalkyl = c‐C6H4, c‐C7H5 from the reaction of substituted 4‐methoxy‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 1‐acetylguanidine in acetonitrile or propan‐2‐ol as solvent, is reported. The acetylamino group of 2‐acetylaminopyrimidines was hydrolyzed under three different conditions to afford the corresponding free 2‐aminopyrimidines.

The synthesis of aminoazobenzenes and the effect of intermolecular hydrogen bonding on their photoisomerization

Two series of azobenzene derivatives were synthesized so as to investigate the effects of intermolecular hydrogen bonding on their photochemistry. Photoisomerization in polymer matrices was investigated under various irradiation conditions using UV pulsed laser light. Rate constants were calculated according to equations for reversible photoisomerization. Although aminoazobenzenes exhibited faster photoisomerization and larger integral rate constants than the corresponding acetylamino derivatives, the latter compounds displayed faster conversion from the trans to the cis form owing to potential intermolecular hydrogen bonding interaction between the acetylamino groups. Long alkyl chain azobenzenes possessed faster photoisomerization rates than those with short alkyl chains.

Synthesis and spectroscopic properties of novel azo dyes derived from phthalimide

A set of azo dyes has been synthesised using N‐substituted phthalimides as diazo components. 3,5‐Dibromo‐N‐substituted‐phthalimidylazo derivatives were cyanated by cyanodehalogenation to give dicyano analogues. All of the synthesised intermediates and dyes have been characterised by mass spectrometry, 1H‐NMR or elemental analyses. The gamut of colour of the prepared dyes spanned much of the visible spectrum: absorption maxima of the dyes in formamide were observed in the range 436 to 609 nm. Consistent with results seen in previous studies of non‐phthalimido monoazo disperse dyes, replacement of dibromo groups with dicyano functions in the phthalimide‐based set led to large bathochromic shifts in absorption maxima, as did the introduction of acetylamino groups onto the coupler ring ortho to the azo link. However, switching an N‐propyl function on the imido ring for a benzyl or 3‐cyanopropyl substituent had little effect on absorption maxima. Good correlations between the observed absorption maxima of certain dyes and those of model analogues predicted by Pariser–Parr–Pople molecular orbital calculations were observed when steric effects were absent.

Complexation of heavy metals by crosslinked chitin and its deacetylated derivatives

Chitin was crosslinked using diisocyanatohexane (HDI), trimellitic anhydride (TMA), and dibromodecane (DBD), then deacetylated in strong aqueous alkali. This led to a product with amine functional groups on the exposed surface of the crosslinked chitin, which could be utilized for complexation with heavy metals. Thus, a key feature of the crosslinked derivatives prepared was that only the hydroxy groups were utilized in the crosslinking reaction, and the acetylamino groups of chitin were hydrolyzed only after the crosslinking was accomplished. This ensured that all amino groups of the chitosans so produced would be available for metal complexation, and not partially used up in crosslinking. This proposed advantage was proved by the similar binding observed for heavy metals like Hg (348–372 mg/g), Cu (91–119 mg/g), Zn (71–92 mg/g), Mn (3–10 mg/g), Cd (121–160 mg/g), and Pb (32–86 mg/g) using these crosslinked polymers, whereas the control polymer (uncrosslinked chitosan powder) had complexation values for Hg (348–361 mg/g), Cu (100–106 mg/g), Zn (81–92 mg/g), Mn (4–7 mg/g), Cd (135 mg/g), and Pb (25–59 mg/g). Additionally, in a case where chitosan was crosslinked with HDI, the amino groups were consumed in the crosslinking reaction, and the metal complexation capacity has found to be decreased for Cu (91–109 mg/g), Cd (133 mg/g), and Zn (71–77 mg/g), while remaining nearly the same for Hg (362 mg/g). The literature value for Cu complexation is 59.67 mg/g for chitosan crosslinked with glutaraldehyde. The crosslinked derivatives have the added advantage of insolubility even in low pH aqueous media, making their repeated re-use possible. Further, these crosslinked derivatives could be used in powder form, and the additional step of preparing beads was found to be not necessary for ease of separation of the crosslinked powder by filtration. The binding capacity of various crosslinked chitin and deacetylated derivatives for Cu, Cd, Hg, Zn, Mn, and Pb was in the region of 100, 140, 360, 88, 5, and 60 mg/g (rounded off values) of polymer, respectively, very close to the values obtained for uncrosslinked chitosan. The metal binding for crosslinked chitosan was slightly lower than that of crosslinked chitin and deacetylated derivatives, due to use of some amino groups in crosslinking. For Cu ions, the Langmuir equation was found to be the best fit for HDI crosslinked deacetylated chitin and TMA crosslinked deacetylated chitin. The morphological studies conducted using WAXRD are in close agreement with the metal complexation data, showing complete loss of original chitosan peaks for the heavily complexed derivatives, and minor changes for the weakly complexed metals.

Recognition of Dicarboxylic Acid by 6,6′-Dipivaloylamino-3,3′-bipyridine and the Supramolecular Solid State Locking of the Carboxyls in the anti Form

A new crystal-engineering motif has been developed where a ditopic receptor 1 having anti binding hindered pyridine pivaloylamide groups instead of normally used acetylamino groups shows a novel anti–anti hydrogen bonded polymeric supramolecular complex giving rise to hydrogen bonded stair like polymeric ribbon structure between the receptor pyridine amides and the carboxyl groups of the guest substrate (1,4-phenylenediacetic acid).

Synthesis of novel sunflower-like silica/polypyrrole nanocomposites via self-assembly polymerization

Novel sunflower-like organic–inorganic composites consisting of spherical silica and smaller conductive polypyrrole particles were successfully prepared through an in situ self-assembly polymerization process by choosing chitosan as a modifying agent of silica surface. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that on the surface of individual silica particle polypyrrole nanoparticles were anchored perfectly. The sunflower-like silica–polypyrrole composites exhibited conductivity of 8 S cm −1 and colloid stability because of the special surface morphology. Adsorbed chitosan chain may play a dual-role of both providing the active sites for formation of the polypyrrole particles on silica and acting as a stabilizer of the silica–polypyrrole particles. Hydrogen-bonding interaction between the acetylamino group of chitosan and hydrogen atom on nitrogen of polypyrrole is a determining parameter in the former case.

Incorporation of N2-Deoxyguanosine Metabolic Adducts of 2-Aminonaphthalene and 2-Aminofluorene into Oligomeric DNA

In previous work we described an efficient procedure for the synthesis of the respective N2 and N6 adducts of 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) derived from a series of aminoaryl compounds. We now outline methods for the site-specific introduction into oligomeric DNA of the adducts dG-N2-AN (6), dG-N2-AAN (7), dG-N2-AF (8), and dG-N2-AAF (9) derived from 2-aminonaphthalene (2-AN) or 2-aminofluorene (2-AF). For the 2-AN adduct 7, containing an acetylamino group, the 5'-O-4,4'-dimethoxytrityl- (DMT-) 3'-O-phosphoramidite (14) required for automated DNA synthesis was synthesized in high yield via the sequence 10-->11-->14. On the other hand, introduction of the desacetyl adduct 6 into oligomeric DNA was accomplished via the N-trifluoroacetyl-DMT-phosphoramidite derivative 18. This involved a similar sequence (10-->15-->18) except that the order of the reactions was changed to avoid a decomposition that occurred when the silyl-protected amino derivative 11 was treated with trifluoroacetic anhydride. In the 2-AF series the 5'-O-DMT-3'-O-phosphoramidites 27a and 27b, related to 8 and 9, were prepared by similar methods. Again, however, the order of the reactions was changed to avoid the extreme insolubility associated with the N2-[3-(2-acetylaminofluoren-3-yl)]dG (dG-N2-AAF, 9) adduct that we had noted previously. The incorporation into oligomeric DNA of the acetylamino compounds 7 and 9 proceeded smoothly and in high yield (95-100%). By contrast, the trifluoroacetyl analogues led in both the naphthyl and fluorenyl series to a mixture of oligomers containing the desired free amino adduct (6 or 8) accompanied by the N-acetyl adduct (7 or 9, respectively, after the deprotection step), indicating secondary acetylation by the capping agent acetic anhydride.

Analysis of the carbohydrate binding specificity of the mushroom Pleurotus ostreatus lectin by surface plasmon resonance

The sugar binding specificity of the mushroom Pleurotus ostreatus lectin (POL) was analyzed by surface plasmon resonance. The lectin was immobilized to a sensor chip, and asialo-bovine submaxillary mucin (asialo-BSM), one of the most potent inhibitors in the hemagglutination inhibition assay, tightly bound to the lectin. The binding specificity of various mono- or oligosaccharides to the lectin was evaluated by the coinjection method. The dissociation of asialo-BSM was promoted by injection of some haptenic saccharides. For the most part, the order of acceleration ability of the sugars to the dissociation in the coinjection experiment agreed with that of the inhibitory potency of each sugar evaluated by the hemagglutination inhibition assay. In conclusion, POL recognized a galactosyl residue, and the specificity was increased by substitution at the C-2 position of the galactosyl residue with a fucosyl or acetylamino group. This method using the coinjection method proved useful in analysis of carbohydrate-lectin binding specificity.