Tautomers solvent effects

In addition to the rather scattered data reported in the previous survey (76AHCSl,p. 510), a few new studies appeared on purine-6- and -2-thiones. Tire MO calculations of solvent effects (AMl-SMl and AM1-SM2) on the tautomerism of 6-thiopurine indicated that l//,9//-tautomer 7a is greatly stabilized in aqueous solution [94THE(309)137].Tlie same results were obtained experimentally from UV and and NMR studies (75JA3215, 75JA4627,75JA4636). 

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

In a combined experimental/computational study, the vibrational spectra of the N9H and N7H tautomers of the parent purine have been investigated [99SA(A) 2329]. Solvent effects were estimated by SCRF calculations. Vertical transitions, transition dipole moments, and permanent dipole moments of several low-lying valence states of 2-aminopurine 146 were computed using the CIS and CASSCF methods [98JPC(A)526, 00JPC(A)1930]. While the first excited state of adenine is characterized by an n n transition, it is the transition for 146. The... 

Once such effects had been noted, it became necessary to interpret the observed results and to classify the solvents. The earliest attempts at this were by Stobbe, who reviewed the effects of solvents on keto-enol tautomers [4]. Since then many attempts have been used to explain solvent effects, some based on observations of chemical reactions, others on physical properties of the solvents, and yet others on spectroscopic probes. All of these have their advantages and disadvantages and no one approach can be thought of as exclusively right . This review is organized by type of measurement, and the available information is then summarized at the end. 

Transient absorption experiments have shown that all of the major DNA and RNA nucleosides have fluorescence lifetimes of less than one picosecond [2—4], and that covalently modified bases [5], and even individual tautomers [6], differ dramatically in their excited-state dynamics. Femtosecond fluorescence up-conversion studies have also shown that the lowest singlet excited states of monomeric bases, nucleosides, and nucleotides decay by ultrafast internal conversion [7-9]. As discussed elsewhere [2], solvent effects on the fluorescence lifetimes are quite modest, and no evidence has been found to date to support excited-state proton transfer as a decay mechanism. These observations have focused attention on the possibility of internal conversion via one or more conical intersections. Recently, computational studies have succeeded in locating conical intersections on the excited state potential energy surfaces of several isolated nucleobases [10-12]. 

The tautomerism between 2-pyridinethione and 2-pyridine thiol has also been examined using variable temperature IR spectroscopy <2002JOC9061>. No evidence for the S-H stretch was observed in a range of solvents and this was determined computationally to be a solvent effect the thiol form is more stable in the gas phase but the thione is more stable in solution. (The effect of phase on the tautomers of 2-hydroxy, 2-amino-, and 2-thiopyridine has also been studied by infrared spectroscopy <2001SAA2659>.) Dimerization is also observed, with the indication that the thione dimer predominates, in contrast with the computational studies described above. 

Thiono-mercapto and amino-imino tautomerism of azines. In the same heterocyclic systems, the stability of thiols with respect to the corresponding thione form is considerably higher than hydroxy derivatives with respect to their oxo forms. In the gas phase 2- and 4-mercaptopyridine are the major tautomers, e.g., 191. 15N NMR spectroscopy is useful for estimating the tautomeric composition of mercaptopyridines in solution. 2-Mercaptopyr-idine in acetone or methanol and 4-mercaptopyridine 191 in methanol or acetone/DMSO were estimated to be ca. 95% in the thione form, e.g., 192. This solvent effect can be attributed to the polarity of the thione tautomers <2006AHC(91)1>. 

Gas-phase NMR spectroscopy has been used to obtain equilibrium constants and rate constants for many low-energy molecular processes. These data have been used to address questions regarding the relative stability of conformers and tautomers in the gas phase, the kinetics of exchange processes in the gas phase, and the direction and magnitude of solvent effects on these equilibria and processes. Most of the studies have appeared in the last 10 years. Continued progress in NMR instrumentation and techniques as well as considerable recent developments in kinetic theory ensure that the next 10 years will see many novel applications of gas-phase NMR spectroscopy. 

Wamke I, Ay S, Brase S, Furche F (2009) Chiral cooperativity and solvent-induced tautom-erism effects in electronic circular dichroism spectra of [2.2]paracyclophane ketimines. J Phys Chem A 113 6987-6993... 

Amino acids, the building blocks of proteins, can exist in two principal tautomeric forms. In aqueous solution, the naturally occurring a-amino acids are found in their zwitterionic form 42Z, but in the gas phase, the neutral form 42N is the only structure observed. This substantial solvent effect is understood in terms of the dipole moments of the tautomers. The dipole moment of the zwitterion is very large and is favorably stabilized by electrostatic interactions with the polar water molecules. In the absence of the polar environment (the gas phase), the charge separation of the zwitterion is unsustainable and only the neutral form exists. 

---