Heterocyclic Residues Research Articles

Metal ion – biomolecule interactions. Part 16. C(2)-H isotopic exchange in Co(III)-coordinated imidazoles

Transition-metal-bound imidazoles are suitable models for evaluating the roles of metal ions in biomolecules having the imidazole moiety and similar heterocyclic residues as part of their structure. Such studies provide useful insights into metal–biomolecule interactions in biological systems, especially when the lability of the metal–ligand bond is substantially reduced, such that the identity of the metal–ligand complex is preserved during the course of the reaction under investigation. The present paper reports on a kinetic study of tritium exchange from the C(2) position of the imidazole moiety in the substitution-inert complex cations [Co(NH3)5[2-3H]-imidazole]3+ (1) and [Co(NH3)5-1-methyl-[2-3H]-imidazole]3+ (2). Rate–pH profiles have been determined in aqueous solution at 60 °C. Both substrates are believed to react through rate-determining attack of hydroxide ion (kM+ pathway) at C(2)-T. Dissection of the kinetic data reveals an additional pathway for 1 consequent upon deprotonation of its pyrrole-like N-H(T) to yield 3, which is then attacked by hydroxide at C(2) (kM pathway). The ratio kM+/kM = 103 that is obtained is in accord with the expected reduced reactivity of 3. Comparison of the present data with those reported for a variety of heterocyclic substrates shows that the order of reactivity, protonated [Formula: see text] metal ion coordinated [Formula: see text] neutral form of substrates, prevails. The superiority of the proton over metal ions in catalyzing isotopic hydrogen exchange is attributed to its larger ground state acidifying effect coupled with the greater transition state stabilization it affords, relative to metal ions. The exchange reaction of 3 via the kM pathway is the first example of a reactive anionic species in which the negative charge is located α to the exchanging C-H. Keywords: tritium exchange, cobalt (III)-coordinated imidazoles.

Synthesis and transformations of some (heteroaryl)acetylazides, (heteroaryl)methyl isocyanates and alkyl (heteroaryl)methyl carbamates

AbstractThe synthesis of two complex acetyl azides 6 and 10 having an heteroaryl residue bound to the acetyl group through the ring nitrogen, and their further transformations into the corresponding carbamates 7a‐b and 11a‐b and isocyanates 16 and 14 are described. Hydrolysis of these products results in the elimination of the substituted methyl group from the heterocyclic residue and formation of 1‐unsubstituled heterocycles. A similar transformation was also observed under mass measurement conditions.

Pyrylocyanines. 30. Unsymmetrical 4,6,4?,6?-tetraphenyl-substituted 2-pyrido-2-pyrylocyanines with trimethylene groupings in the chromophore

The reaction of methylamine with symmetrical 4,6,4′,6′-tetraphenyl-substituted 2-pyrylopolycarbocyanines, in which both a positions of the polymethine chain are linked to the β positions of the heterocyclic residues by trimethylene groups, was used to synthesize the corresponding pyridopyrylocyanines. The effect of trimethylene groupings in the 2-pyridocyanines on this transformation was examined. The principles involved in the color of the synthesized pyridopyrylocyanines were studied.

Preparation of heteroaryl phenylmethanes and a 13C and 15N NMR spectroscopic study of their conjugate carbanions. Rotational isomerism and charge maps of the anions and ranking of the charge demands of the heterocycles

2-Benzylpyridazine, 4-benzylpyrimidine, 2-benzylpyrimidine and 2-benzylpyrazine, (5–8), have been prepared in order to study their 13C and 15N spectra and those of their conjugate carbanions (1–4). These systems are aza-homologues of the previously reported benzylpyridines and have been considered to evaluate the effect of aza-substitution upon rotational isomerism and charge maps in the anions. Two synthetic approaches have been followed: (i) decarboxylation of α-(heteroaryl)phenylacetic acids, in turn obtained by nucleophilic substitution of phenylacetonitrile anion on the pertinent halogenoazine (or a correspondingly available derivative); (ii) by nucleophilic substitution of benzyl (tributylphos-phonium)ylide on the pertinent halogenoazine. The 13C and 15N NMR data for 1–4 indicate that, at room temperature, there is slow rotation about the bond between the carbanionic carbon and the carbon atom of the heterocycle: this generates geometrical isomerism in the anions 1–4. The NMR data are treated with the π-charge–shift equations (1)–(4) to obtain the local variations of the π-electron density. By evaluating, in anions 1–4, the fraction of π-charge transferred to the heterocycle from the carbanionic carbon it is possible to obtain the charge demands, cx of the heterocycles, and thus rank them on the same scale as primary organic functionalities. It is found that the 4-pyrimidyl is the strongest electron-withdrawing heterocyclic residue, comparable with the acetyl group.

5-Hetaryl-substituted 2-methyleneindolines and polymethine dyes based on them

2-Methyleneindolines containing benzazole residues at the 5-position were synthesized and polymethine dyes were obtained from them. The bathochromic shifts induced by the introduction of heterocyclic residues into indocyanines exceed the similar shifts induced by the same heterocycles in thio and quinocyanines.

Correlation of polymethine dye basicity with parameters of the terminal heterocyclic nuclei

The basicity values of symmetrical polymethine dyes have been compared and correlated with a variety of parameters obtained both experimentally or derived by calculations, as well as with parameters obtained by quantum mechanical methods, characterizing the electron-donating abilities of the terminal heterocyclic residues. Linear correlations have been derived for the first time between the thermodynamic and spectral characteristics of these compounds and effective parameters of the heterocyclic nuclei. The basicity has been shown to be a universal characteristic not only of the end group but of the molecule as a whole.

Mass spectrometry of nitrogenous heterocycles. 1. Mass spectrometric evaluation of stability of tetrahydropyrazines annelated to five- and six-membered heterocycles

Based on a study of electron impact mass spectra of a large number of tetrahydropyrazines, which are joined to five- and six-membered heterocyclic and carbocyclic residues, the trends which characterize the stability of these condensed systems are found. The proposed criteria can be used for evaluation of the chemical stability of these compounds, for example, their propensity toward the reverse dissociation reaction.

Mesoionic compounds with a bridging nitrogen atom

Mesoionic thiazoloazinium oxides -have been synthesized previously [i], and their spectral characteristics have been investigated [2]. Since these compounds absorb in the visible region of the spectrum (440-600 nm), and since the effective length of the heterocyclic residues in these dyes [3] is quite large (with respect to their effect on color, the heterocyclic residues are equivalent to about 6-7 vinylene groups [4, 5]), it was of interest to us to prepare a vinylogous series of symmetrical polymethine dyes based on these derivatives, and to study their spectral characteristics.

Radiation Damage to Histone H2A by the Primary Aqueous Radicals

Histone H2A has been examined for radiation-induced changes in structure and in amino acid composition. The effects of the individual radical intermediates--the hydroxyl radical, solvated electron, and superoxide radical--have been determined by irradiating in dilute aqueous solution under controlled environmental conditions. Amino acid analysis of irradiated histone H2A shows a selective attack on a few residues; only the aromatic residues, phenylalanine and tyrosine, and the heterocyclic residue, histidine, are significantly decreased. A significant increase in aspartic acid is also observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the hydroxyl radical is the effective radical for promoting changes in protein structure.

ChemInform Abstract: PYRYLOCYANINES. 21. UNSYMMETRICAL α‐PYRYLO‐ AND α‐PYRIDOCYANINES

AbstractEs wird der Einfluß von Elektronendonor‐ und Elektronenakzeptor‐Gruppen wie ‐OMe bzw. ‐NO2 in Farbstoffen der allgemeinen Formel (I) auf verschiedene physikalische Eigenschaften untersucht.

Pyrylocyanines. 21. Unsymmetrical ?-pyrylo- and ?-pyridocyanines

(2-Pyrylo)- and (2-pyrido)(indo)trimethinecyanines containing both electron donor and electron acceptor substituants in the heterocyclic rings have been synthesized. It has been shown that the 4,6-diphenyl-2H-pyran nucleus confers less basicity (electron donor characteristics) than the 1,3,3-trimethylindoline segment. It has also been shown that the introduction of substituents to the heterocyclic residues of unsymmetrical dyes allows one to manipulate their electronic asymmetry over a wide range up to a change in the distribution of charge from one ring to another.

Pyrylocyanines. 19. Symmetrical pyrylocyanines based on 3,4-polymethylene-2,6-diphenylpyrylium salts

Symmetrical 2,6,2′,6′-tetraphenyl-substituted pyrylo-4- and thiopyrylo-4-cyanines in which both α positions of the polymethine chain are bonded to the β positions of the heterocyclic residues by ethylene or trimethylene groups were synthesized. The introduction of bridged groupings gives rise to a bathochromic effect, which is greater for ethylene groups than for trimethylene groups.

Pyrylocyanines. 18. Unsymmetrical flavylocyanines on the basis of methoxysubstituted 4-methylflavylium salts

Unsymmetrical flavyloindotrimethylidynecyanines in which a methoxy group is located alternately in the 5, 6, 7, 8, 2′, 3′, and 4′ positions of the flavylium ring were synthesized. An increase in the electron-donor character of the heterocyclic residue generally leads to a bathochromic shift of the absorption bands of the dyes and a decrease in the widths of these bands and the ratios of the intensities of the short-wave and long-wave maxima in them.

Pyrylocyanines. 14. Unsymmetrical pyrylocyanines based on 2,3-polymethylene-4,6-diphenylpyrylium salts

Unsymmetrical 4,6-diphenylpyrylo-2-carbo- and dicarbocyanines, as well as the analogous pyridocyanines, containing 3-ethylbenzothiazolium and 1,3,3-trimethyl-3H-indolium residues and an ethylene or trimethylene bridging grouping between the α position of the polymethine chain and the β position of the pyrylium or pyridinium residue were synthesized. The introduction of bridging groups is generally accompanied by a bathochromic effect and intensification (in the pyrylocyanine series) or weakening (in the pyridocyanine series) of the fine structure of the absorption bands. On the basis of the deviations calculated from the centers of the absorption bands and the dependences of the vinylene shifts and the absorption band widths on the structure of the dyes it was concluded that the trimethylene bridging groups in the examined cases increase the electron-donor character of the heterocyclic residues in the dyes more markedly than the ethylene bridging groups.

Marqueurs Á spin construits directement sur le squelette carboné de sucres

Treatment of aldehydo-sugars with 2,3-bis(hydroxyamino)-2,3-dimethylbutane gave the corresponding 1,3-dihydroxyimidazolidines. Oxidation of these compounds gave, successively, unstable, free radicals having a 3-hydroxyimidazolidine 1-oxyl structure, then stable, free radicals having a 2-glycosyl-2-imidazoline 3-oxide 1-oxyl structure, which were reduced to stable 2-glycosyl-2-imidazoline 1-oxyl compounds. The orientation of the two last-named series of compounds around the σ bond between carbohydrate and heterocyclic residues that bears the radical centre is indicated by the value of the hyperfine coupling aH of the carbohydrate proton nearest to the nitrogenous heterocyclic residue. The study of numerous compounds of both series shows that the value of the hyperfine coupling depends greatly on the structure of the carbohydrate residue. A general explanation based on the preponderance of eclipsed forms and on the primary influence of steric hindrance due to the substituents of the carbohydrate residue is proposed. This study also gives some indirect information on the conformation of diamagnetic compounds that show little sterical difference, and about which 1H-n.m.r. spectroscopy does not provide useful information.

Pyrylocyanines. 13. Symmetrical pyrylocyanines based on 2,3-polymethylene-4,6-diphenylpyrylium salts

Symmetrical 4,6,4′,6′-tetraphenyl-substituted pyrylo-2-, thiopyrylo-2-, and pyrylo-2-cyanines in which both α positions of the polymethine chain are bonded to the β positions of the heterocyclic residues by ethylene and trimethylene groups were synthesized. The introduction of bridged groupings is accompanied by intensification of the fine structure and bathochromic and hypsochromic effects in the absorption spectra; the former effect is greater and the latter effect is smaller in the case of ethylene groups. The steric and electronic effects of these groups are discussed with the aid of PMR spectroscopy and quantum chemistry.

Direct introduction of heterocyclic residues in the oxindole ring

It has been reported [1] that salts of some N-acyloxyheteroaromatic cations hetarylate 1-methyloxindole in situ. It seemed extremely probable that the salts of more electrophilic N-acylheteroaromatic cations also can be used for the direct introduction of a heterocyclic residue in the oxindole ring, especially since similar salts have proved to be suitable for the hetarylation of the most diverse CH acids with pKa ⩽ 20–21 [2].

Substrate specificity of ribosomal peptidyltransferase. Effect of modification in the heterocyclic, carbohydrate and amino acid moiety of 2'(3')-O-L-phenylalanyladenosine.

The chemical synthesis of 2'(3')-O-L-phenylalanyl derivatives of nebularine (Ld), 6-methoxynebularine (Ih), N6,N6-dimethyladenosine (Lk), 6-methylthionebularine (Lo), 8-bromoadenosine (Lr), tubercidin (Iu), and 3'-O-L-phenylalanyl derivatives of 1-(beta-D-arabinofuranosyl)cytosine (IIIg) and 9-(beta-D-arabinofuranosyl)adenine (IIIl) is described. 2'(3')-O-(3-Phenyl)propionyladenosine (Iv) was obtained by reaction of adenosine with ethyl 3-phenylorthopropionate and subsequent hydrolysis of the orthoester intermediate IV with formic acid. Compounds Id, Ih, Ik, Io, and Iu were active in the release of Ac-Phe from N-Ac-Phe-tRNA-poly(U)-70S ribosome complex: at 0.01 mM the release of Ac-Phe was 50-100% of that of A-Phe. At 1 mM, compounds Ir and IIIg released 30 and 25% of Ac-Phe relative to A-Phe whereas derivatives Iv and IIIl were virtually inactive. The results indicate the following conclusions regarding ribosomal peptidyltransferase activity of 2'(3')-O-aminoacyl nucleosides: (a) the presence of the 2'-hydroxy group in the ribo configuration is more important for a highly active substrate (A-Phe) than for one of moderate activity (C-Phe); (b) the heterocyclic (purine) residue is in the anti conformation although this requirement is not absolute; (c) the presence of the amino group of the aminoacyl moiety is required; (d) acceptor activity is dependent upon the substituent in the position 6 of the purine moiety.

Structure-activity relationships in reactivators of organophosphorus-inhibited acetylcholinesterase. 9. N-Heterocyclic acraldoximes methiodides.

N-Heterocyclic acraldoximes methiodides, where the heterocyclic residues are 2-, 3-, and 4-pyridyl, 2-(1-methyl)imidazolyl or 4-pyrimidyl, were prepared and tested for their reactivating potency on acetylcholinesterase inhibited from diisopropylphosphorofluoridate (DFP). The in vitro testing revealed that the new compounds are good reactivators of the phosphorylated electric eel cholinesterase. The structure-activity relationships are briefly discussed.

Aromatization reactions of some N-acyl-1,2-dihydroquinolines and isoquinolines

The proton and hydride lability of the α-hydrogen atom in various α-substituted N-acyl-1,2-dihydroquinolines and N-acyl-1,2-dihydroisoquinolines was investigated. It was shown that splitting out of both a hydride ion and an α-substituent as carbanions is possible in the presence of strong electron-acceptor substituants in the α position under the influence of electrophilic agents. A new transhetarylation reaction consisting in the migration of the heterocyclic residue from one compound with a labile hydrogen atom to another was found.