Properties of a new fluorescent cytosine analogue, pyrrolocytosine.
Pyrrolocytosine is a novel, environment sensitive, fluorescent base that can be used in place of cytosine as a fluorescent marker in nucleic acids. In this work the results of a detailed computational investigation into the hybridization and photochemical properties of the base are reported. The interaction energy of the base pair formed between pyrrolocytosine and guanine, calculated at the MP2/6-31G(d,0.25)//HF/6-31G(d,p) level, was found to be -27.2 kcal mol(-1), comparing very favorably with the value calculated for the cytosine and guanine base pair, -25.8 kcal mol(-1). The wavelengths for the vertical transitions of pyrrolocytosine and cytosine were determined using both the configuration interaction technique, with singly excited configurations (CIS) and time-dependent density functional theory using the B3LYP functional (TDB3LYP). It was found that the spacing between the first pipi state and the first npi state was significantly larger in the case of pyrrolocytosine than cytosine, providing a rationale for the higher fluorescence quantum yield of the former. Hydrogen bonding of pyrrolocytosine to guanine did not affect the predicted fluorescence properties of pyrrolocytosine whereas stacking guanine above pyrrolocytosine, in a manner appropriate to B-form DNA, significantly reduced the predicted fluorescence. Calculations on the two base systems using the TDB3LYP method produced low-lying charge-transfer states which are not predicted when the CIS method is used and are not thought to be physically meaningful.
Thompson
Katherine C
KC
School of Biological and Chemical Sciences, Birkbeck University of London, Malet Street, London WC1E 7HX, U.K.
Miyake
Norimune
N
D003596:Cytosine / Q000031:analogs & derivatives*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure
D005456:Fluorescent Dyes; D006147:Guanine; D003596:Cytosine