Tautomerism in Neutral Histidine

Histidine is an important natural amino acid, involved in many relevant biological processes, which, because of its physical properties, proved difficult to characterize experimentally in its neutral form. In this work, neutral histidine has been generated in the gas phase by laser ablation of solid samples and its N_εH tautomeric form unraveled through its rotational spectrum. The quadrupole hyperfine structure, arising from the existing three ¹⁴N nuclei, constituted a site‐specifically probe for revealing the tautomeric form as well as the side chain configuration of this proteogenic amino acid.     

Tautomerism in drug discovery

The influence of tautomerism on the precise structure of drugs and thus of their potential to interact with biological systems is discussed from thermodynamic and kinetic aspects. The types of tautomerism encountered in the structure of drugs in current use are surveyed together with the effect of pH, solvent polarity, and temperature.     

Tautomerism in novel oxocorrologens

A novel corrole-type macrocycle, oxocorrologen (2), substituted with hemiquinone groups, has been synthesized. It was found to undergo multiple tautomerism of its exchangeable protons between electronegative atom sites at the macrocyclic core (nitrogen atoms) and periphery (phenol oxygen atoms). Alkylation at one macrocyclic nitrogen atom with a 4-nitrobenzyl group gave 3, which can exist in only two tautomeric forms depending on the solvent. Tautomerism has been studied by means of (1)H NMR spectroscopy in a variety of solvents and solvent mixtures. Tautomer structure assignments have been supported by DFT calculations of the relative energies of the tautomers. X-ray crystallography of the N-nitrobenzyl derivative has revealed that intramolecular hydrogen bonding may be responsible for stabilizing the observed tautomers. The solvent dependence of the tautomerism of 2 and 3 confers solvatochromism. Electrochemical measurements on 2 and 3 in their respective quinone forms have revealed irreversible processes, but indicate that they are both electron-deficient with a small HOMO-LUMO gap and first reduction potentials close to those of fullerene electron acceptors.     

Tautomerism in quinaldyl ketones

The quinaldyl ketone, 4-phenyl-3-(quinolin-2-yl)-butan-2-one was prepared by two methods: (a) benzylation of 1-(1H-quinolin-2-ylidene)propan-2-one in the presence of sodium hydride in dimethylformamide and (b) by the benzylative demethoxycarbonylation of methyl 2-(1H-quinolin-2-ylidene)-3-oxobutanoate in the presence of lithium bromide in hexamethylphosphoramide at 135°. In the absence of acid, the compound exists exclusively in the tautomeric form, 4-phenyl-3-(1H-quinolin-2-ylidene)butan-2-one.     

Tautomerism in large databases

We have used the Chemical Structure DataBase (CSDB) of the NCI CADD Group, an aggregated collection of over 150 small-molecule databases totaling 103.5 million structure records, to conduct tautomerism analyses on one of the largest currently existing sets of real (i.e. not computer-generated) compounds. This analysis was carried out using calculable chemical structure identifiers developed by the NCI CADD Group, based on hash codes available in the chemoinformatics toolkit CACTVS and a newly developed scoring scheme to define a canonical tautomer for any encountered structure. CACTVS’s tautomerism definition, a set of 21 transform rules expressed in SMIRKS line notation, was used, which takes a comprehensive stance as to the possible types of tautomeric interconversion included. Tautomerism was found to be possible for more than 2/3 of the unique structures in the CSDB. A total of 680 million tautomers were calculated from, and including, the original structure records. Tautomerism overlap within the same individual database (i.e. at least one other entry was present that was really only a different tautomeric representation of the same compound) was found at an average rate of 0.3% of the original structure records, with values as high as nearly 2% for some of the databases in CSDB. Projected onto the set of unique structures (by FICuS identifier), this still occurred in about 1.5% of the cases. Tautomeric overlap across all constituent databases in CSDB was found for nearly 10% of the records in the collection.     

Phosphorotropic Tautomerism in Amidines

Abstract

We have discovered and systematically studied the fast reversible 1,3-rearrangements phosphorus-containing groups with tri-, tetra- and pentacoordinate phosphorus in amidines by means of NMR ¹H, ¹³C, ³¹p spectroscopy.     

Tautomerism in isomeric oxypurines

Starting with the assumption, based upon infrared spectroscopy evidence, that the oxypurines exist essentially in the keto form, calculations are performed by the CNDO/2 and the SCF MO CI methods in order to determine the most stable tautomers of these molecules with respect to the possible sites of attachement of the protons upon available ring nitrogens, and in order to evaluate their principal electronic properties. The calculations predict correctly the most stable tautomers, account satisfactorily for the observed ultraviolet absorption spectra and indicate that dipole moment measurements may be a particularly useful tool for the identification of the tautomers.

---

Zusammenfassung Mit der von der UV-Spektroskopie gestützten Annahme, da\ die Oxypurine in der Keto-Form vorliegen, werden nach der CNDO/2-und der SCF MO CI-Methode die stabilsten tautomeren Formen dieser Moleküle bezüglich der möglichen Anlagerung von Protonen an die verfügbaren Stickstoffatome im Ring und ihre prinzipiellen elektronischen Eigenschaften berechnet. Die Rechnungen geben in übereinstimmung mit dem Experiment die stabilsten Tautomeren richtig wieder, zeigen eine gute übereinstimmung mit den UV-Absorptionsspektren und lassen darauf schlie\en, da\ das Dipolmoment eine zur Identifikation der Tautomeren geeignete Grö\e ist.

---

Résumé Alors que la spectroscopie ultraviolette n'est pas capable d'indiquer sans ambiguité si les oxypurines existent préférentiellement sous la forme cétonique ou énolique, la spectroscopie infrarouge décide, elle, en faveur de la forme cétonique. Partant de cette constatation on effectue des calculs CNDO/2 et SCF MO CI pour déterminer les formes tautoméres les plus stables de différentes oxypurines par rapport aux sites de fixation de protons sur les azotes du cycle. Les calculs prédisent correctement dans chaque cas les tautoméres les plus probables, permettent de rendre compte de leurs spectres d'absorption et montrent l'utilité des mesures des moments dipolaires pour l'identification de ces tautoméres.

---

---

This work was sponsored by the RCP No. 173 of the Centre National de la Recherche-Scientifique and grant No. 67-00-532 of the Délégation Générale à la Recherche Scientifique et Technique.     

Tautomerism of rhodanine

Semiempirical (MINDO/3, AM1, PM3, MNDO) and ab initio (4-31G and 4-3IG + dAO/S basis sets) calculations on the relative stabilities and structures of the five potential tautomeric forms of rhodanine are reported. It is shown that all methods (excepting PM3) predict as most stable 2-thioxo-4-thiazolidinone. These results correspond to the known experimental data. The infrared spectrum of rhodanine was recorded for the region 4000-150 cm^–1, and the characteristic bands were compared with AM1 and 4-31G + dAO/S calculated frequencies. The transition states between five pairs of all possible tautomeric forms of the rhodanine were found by the AM1 method.     

Tautomerism in acyl tetronic acids

The tautomeric structures of some acetyl tetronic acids are studied by NMR analysis.     

Phosphorotropic Tautomerism in Amidine Systems

Abstract

During the last years considerable progress was made in the study of phosphorotropic tautomeric transformations, which involves quick reversible migrations of phosphorus groups between nucleophilic centers of molecule. Phosphorotropic systems may serve a s simple and clear models for study of the mechanism of substitution reactions at the phosphorus atom.     

Tautomerism in some quinaldyl sulfones

A series of quinaldyl sulfones was synthesized and their tautomeric composition was determined by ¹H nmr.     

Tautomerism in silicon-containing free radicals

Silicon-containing free radicals with 3,6-di-t-butylpyrocatechinic ligands have been investigated by ESR method. Intramolecular migrations of free valence and bond was found for these systems. It was considered in terms of intramolecular radical substitution.     

Tautomerism in 3-nitrotetronic acids

The controversial structure of the title compounds has been established. The previously reported strong intramolecular hydrogen bond was found to be absent.     

Tautomerism of 1,5-dibenzazolylformazans

The structures of new symmetrical and asymmetrical 1,5-dibenzazolylformazans were investigated by IR and electronic spectroscopy. It is shown that 1,5-dibenzimidazolylformazans, regardless of the substituent in the 3 position (methyl, phenyl), display the presence of the tautomeric imino form in solutions. 1,5-Dibenzothiazolylformazans display a high tendency to form chelate forms. The stability of the chelate increases on passing from the 3-methyl to the 3-phenyl derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 699–701, May, 1973.     

Benzene Oxide-Oxepin Valence Tautomerism

Benzene oxide and the potential 8π-electron system oxepin exist in valence-tautomeric equilibrium with each other, to which both components contribute to approximately the same extent. NMR spectroscopic measurements show that the equilibrium is rapidly established (activation energies of the forward and reverse reactions 9.1 and 7.2 kcal mole^?1, respectively). The present knowledge of the properties of oxepin justifies its classification as a “heterotropilidene”. Benzene oxide-oxepin represents a system having fluctuating bonds, the equilibrium of which can be displaced from one extreme to the other by means of suitable substituents. The oxide component determines the reactions of the system with most agents. With 1,6-oxido[10]annulene, which is formally a 2,7-bridged oxepin, the oxepin character is completely suppressed by the formation of a delocalized 10π-electron system extending over the C₁₀ perimeter. The existence and aromatic character of 1,6-oxido[10]-annulene give rise to the conception of a homologous series of oxygen bridged annulenes (1,6; 8,13-bisoxido[14]annulene, 1,6; 8,17; 10,15-trisoxido[18]annulene etc.), which, like the parent acenes, possess a (4n + 2)π-electron system. Molecular models demonstrate that a considerable flattening of the C_4n+2 perimeter is achievable in the case of a syn or all-syn arrangement of the oxygen bridges, and that the requirement for aromaticity is thus satisfied. This is confirmed in a striking manner by the synthesis and properties of syn-1,6; 8,13-bisoxido[14]annulene.