Cytosine isocytosine

The direct formation of dipyrimidin-5-yl sulfides occurs on treatment of appropriate 5-unsubstituted pyrimidine substrates with sulfur mono- or di-chloride. Thus, reaction of uracil (83 R = H) with sulfur monochloride in boiling formic acid gives diuracil-5-yl sulfide in good yield sulfur dichloride gives a poor yield. Simple derivatives of uracil and barbituric acid undergo similar reactions but not cytosine, isocytosine, 2,4-bismethylthiopyrimidine or pyrimidine-4,6-dione (59). The mechanism is unknown (72AJC2275). 

Owing to the increasing efficiency of computational methods, it has become possible to investigate base pairs in the gas phase and solution simulated by super-molecular approaches with up to six water molecules [98IJQ37, 98JPC(A) 10374, 98JPC(B)9109, 99JST107]. In the cytosine-isocytosine Watson-Crick base pair. 

Roberts et al. (1966) described a similar synthesis cyanoacetaldehyde and guanidine hydrochloride gave 40-80% yields of 2,4-diaminopyrimidine under the conditions of the lagoon model mentioned above. Hydrolysis of diaminopyrimi-dine leads to cytosine, isocytosine and uracil. Thiourea reacts with cyanoacetylene to give 2-thiocytosine however, the yield is considerably lower than with urea or... 

Figure 11. Predicted tautomeric equilibria in cytosine - isocytosine complexes. The area where the different number of water molecules have been placed is colored in grey.

All complexes of cytosine - isocytosine base pairs dramatically change the geometry when they interact with six water molecules. They become strongly nonplanar and adopt a buckling structure. For example, the buckle angle amounts to 3.6", 6.1 , 3.2" and 31.2" for isolated, two-, four- and six-hydrated iCCl complexes, respectively. The same effect has been observed for seven water molecules hydrating the AU complexes. 

Finally we would like to mention the investigation of the so called reverse Watson-Crick isocytosine - cytosine base pair which mimic the parallel strand of the DNA [145]. Among the structures investigated at the MP2/6-31 G(d)//HF/6-3 lG(d) level, the complex presented in Figure 13, which includes the interaction of two rare tautomers, is only 9 Kcal mof less stable than canonical cytosine-isocytosine base pair. Inclusion of the hydration decreases this difference to 6 Kcal-mof. Thus the calculations indicate that possible involvement of minor tautomeric pairs should be considered when considering the structure of a parallel strand of DNA. 

David and Lubineau191 reported the synthesis of pseudocytidine [5-/3-D-ribofuranosylcytosine (270)] and its a anomer by a procedure analogous to that used in preparing pseudouridine.155-157 Thus, 2,4 3,5-di-O-benzylidene-a/de/iydo-D-ribose (223) was condensed with the dilithio derivative of 2-0,4-N-(trimethylsilyl)cytosine, and the resulting, epimeric, acyclic derivatives were subjected to acid-catalyzed cyclization. The anomeric configuration of the free C-nucleosides was ascertained by spectroscopic methods and by their transformation into a- and /3-pseudouridine in the presence of nitrous acid. The anomeric 5-(/3-D-ribofuranosyl)isocytosines have also been prepared by Fox and coworkers.1913... 

Figure 6 15 Important hydrogen-bonding positions for (A) cytosine and (B) isocytosine in hammerhead ribozymes.

An interesting feature was discovered by Sharma and co-workers494,495 in the crystal structure of isocytosine. Two tautomers of isocytosine (42 and 43) exist in an exact 1 1 ratio in the crystal. The tautomers are hydrogen-bonded to each other in a manner analogous to that proposed by Watson and Crick496,497 for the guanine-cytosine pair in DNA. It is worth underlining that the base pair of isocytosine was not obtained by expedient cocrystallization of the two components. It seems therefore probable that both forms 42 and 43 of isocytosine are of approximately equal stability and are present in comparable amounts in solution. 

Information on the tautomerism in thio analogs of cytosine and isocytosine is scanty. After comparing the UV spectra and ionization constants of these molecules with those of their methylated derivatives, Brown and Teitci511 suggested that thiocytosine exists as a mixture of 52 and 55 in aqueous solution, and isothiocytosine exists rather in form 56. As the 1-methyl derivative of isocytosine was not available, the latter conclusion is uncertain. In fact, the 77-SCF MO Cl calculations... 

Schuchmann MN, Naumov S, Schuchmann H-P, von Sonntag J, von Sonntag C (2005) 4-Amino-3Ff-pyrimidin-2-one ("isocytosine") is a short-lived non-radical intermediate formed in the pulse radiolysis of cytosine in aqueous solution. Radiat Phys Chem 72 243-250 Schulte-Frohlinde D, Hildenbrand K (1989) Electron spin resonance studies of the reactions of OH and SO4 radicals with DNA, polynucleotides and single base model compounds. In Minisci F (ed) Free radicals in synthesis and biology. Kluwer, Dordrecht, pp 335-359 Schulte-Frohlinde D, Behrens G, Onal A (1986) Lifetime of peroxyl radicals of poly(U), poly(A) and single- and double-stranded DNA and the rate of their reaction with thiols. Int J Radiat Biol 50 103-110... 

Electron impact mass spectrometry of cytosine and isocytosine derivatives 93WCH51. 

Zhanpeisov, N. U. Sponer, J. Leszczynski, J. Reverse Watson-Crick isocytosine-cytosine and guanine-cytosine base pairs stabilized by the formation of the minor tautomers of bases. An ab initio study in the gas phase and in a water cluster, J. Phys. Ghent. A 1998,102,10374-10379. 

MO methods have calculated that the bond order of the C(5)-C(6) bond in the first triplet of a series of pyrimidines is lower than in the first excited singlets of the corresponding molecules, and have concluded that dimerization of the bases occurs via the triplet state. They divided the pyrimidines into three groups the pyrimidines which are known to be easily dimerizable (uracil, 6-methyluracil, thymine, orotic acid—for these molecules the Pse values in their T state are of the order of 0.09-0.12), those which dimerize not so easily (5-aminouracil, cytosine, 5-methylcytosine—Pge 0.13-0.17), and the bases which do not dimerize at all or only with considerable difficulty (2-thiothymine, Pgg = 0.31 isocytosine, Pgg = 0.39 and 5-nitrouracil). The relative distribution of the bases within groups leads sometimes to only limited agreement with available experimental data. For instance, as the Pgg = 0.085 in T of uracil is lower than Pgg = 0.106 in T of thymine, uracil should dimerize more easily than thymine, a conclusion in disagreement with experiment. ... 

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