Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-Analogues in Solution

Abstract

The steady-state and time-resolved photochemistry of the natural nucleic acid bases and their sulfur- and nitrogen-substituted analogues in solution is reviewed. Emphasis is given to the experimental studies performed over the last 3-5 years that showcase topical areas of scientific inquiry and those that require further scrutiny. Significant progress has been made toward mapping the radiative and nonradiative decay pathways of nucleic acid bases. There is a consensus that ultrafast internal conversion to the ground state is the primary relaxation pathway in the nucleic acid bases, whereas the mechanism of this relaxation and the level of participation of the (1)πσ*, (1) nπ*, and (3)ππ* states are still matters of debate. Although impressive research has been performed in recent years, the microscopic mechanism(s) by which the nucleic acid bases dissipate excess vibrational energy to their environment, and the role of the N-glycosidic group in this and in other nonradiative decay pathways, are still poorly understood. The simple replacement of a single atom in a nucleobase with a sulfur or nitrogen atom severely restricts access to the conical intersections responsible for the intrinsic internal conversion pathways to the ground state in the nucleic acid bases. It also enhances access to ultrafast and efficient inter-system crossing pathways that populate the triplet manifold in yields close to unity. Determining the coupled nuclear and electronic pathways responsible for the significantly different photochemistry in these nucleic acid base analogues serves as a convenient platform to examine the current state of knowledge regarding the photodynamic properties of the DNA and RNA bases from both experimental and computational perspectives. Further investigations should also aid in forecasting the prospective use of sulfur- and nitrogen-substituted base analogues in photochemotherapeutic applications.

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

“…In addition to the excitation wavelength used, glycosylation of the thiopyrimidine chromophore at the N1 position affects the intersystem‐crossing rate (, B. Ashwood, M. Pollum, C. E. Crespo‐Hernández, unpublished results), as has been reported for the canonical nucleobases . Pollum et al .…”

“…Following ultrafast population of the triplet manifold, additional minor relaxation pathways have been routinely observed in the excited‐state dynamics of thiopyrimidine derivatives occurring within tens of picoseconds. Triplet self‐quenching has been reported for 2‐thiocytosine (B. Ashwood, M. Pollum, C. E. Crespo‐Hernández, unpublished results), 2‐thiothymine, 2‐thiothymidine, and 2‐thio‐2′‐deoxythymidine , 2‐thiouracil and 4‐thio‐2′‐deoxythymidine , whereas vibrational cooling dynamics in the T 1 state have been reported for 2‐thiocytosine and 2‐thiocytidine (,B. Ashwood, M. Pollum, C. E. Crespo‐Hernández, unpublished results), 2‐thiothymine, 2‐thiothymidine, and 2‐thio‐2′‐deoxythymidine , 2‐thiouracil (,B.…”

“…Thionation also leads to important changes in the absorption spectrum of the pyrimidine bases (Table ) . As exemplified in Fig.…”

“…Room‐temperature phosphorescence emission has been observed in 2‐thiouracil, 2‐thiouridine, 4‐thiouracil, 4‐thiothymine, 2,4‐dithiothymine, and 4‐thio‐2′‐deoxythymidine with quantum yields on the order of 10 −4 , while fluorescence (ca. 10 −5 ) has been detected in 2‐thiouracil, 2‐thiouridine and 4‐thio‐2′‐deoxythymidine in aqueous solution (B. Ashwood, M. Pollum, C. E. Crespo‐Hernández, unpublished results) . Quantum‐chemical calculations have estimated the adiabatic energy of 2‐thiouracil to be at 349 nm for the lowest 1 π S π* state and between 325 and 369 nm for the 1 n S π* state in vacuum, whereas an adiabatic energy between 358 and 435 nm has been reported from the lowest 3 π S π* state.…”

“… *See previous reviews for absorption and emission properties in other solvents and temperatures . † Wavelength of lowest‐energy absorption band maximum.…”