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Quantum mechanics/molecular mechanics studies on the excited-state decay mechanisms of cytidine aza-analogues: 5-azacytidine and 2′-deoxy-5-azacytidine in aqueous solution
The excited state properties and deactivation pathways of two DNA methylation inhibitors, i.e. , 5-azacytidine (5ACyd) and 2′-deoxy-5-azacytidine (5AdCyd) in aqueous solution, are comprehensively explored with the QM(CASPT2//CASSCF)/MM protocol. We systematically map the feasible decay mechanisms ba...
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Published in: | Physical chemistry chemical physics : PCCP 2023-10, Vol.25 (38), p.26258-26269 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The excited state properties and deactivation pathways of two DNA methylation inhibitors,
i.e.
, 5-azacytidine (5ACyd) and 2′-deoxy-5-azacytidine (5AdCyd) in aqueous solution, are comprehensively explored with the QM(CASPT2//CASSCF)/MM protocol. We systematically map the feasible decay mechanisms based on the obtained excited-state decay paths involving all the identified minimum-energy structures, conical intersections, and crossing points driving the different internal conversion (IC) and intersystem crossing (ISC) routes in and between the
1
ππ*,
1
nπ*,
3
ππ*,
3
nπ*, and S
0
states. Unlike the
1
nπ* state below the
1
ππ* state in 5ACyd, deoxyribose group substitution at the N1 position leads to the
1
ππ* state becoming the S
1
state in 5AdCyd. In 5ACyd and 5AdCyd, the initially populated
1
ππ* state mainly deactivates to the S
0
state through the direct
1
ππ* → S
0
IC or mediated by the
1
nπ* state. The former nearly barrierless IC channel of
1
ππ* → S
0
occurs ultrafast
via
the nearby low-lying
1
ππ*/S
0
conical intersection. In the latter IC channel of
1
ππ* →
1
nπ* → S
0
, the initially photoexcited
1
ππ* state first approaches the nearby S
2
/S
1
conical section
1
ππ*/
1
nπ* and then undergoes efficient IC to the
1
nπ* state, followed by the further IC to the initial S
0
state
via
the S
1
/S
0
conical intersection
1
nπ*/S
0
. The
1
nπ*/S
0
conical intersection is estimated to be located 6.0 and 4.9 kcal mol
−1
above the
1
nπ* state minimum in 5ACyd and 5AdCyd, respectively, at the QM(CASPT2)/MM level. In addition to the efficient singlet-mediated IC channels, the minor ISC routes would populate
1
ππ* to T
1
(ππ*) through
1
ππ* → T
1
or
1
ππ* →
1
nπ* → T
1
. Relatively, the
1
ππ* →
1
nπ* → T
1
route benefits from the spin-orbit coupling (SOC) of
1
nπ*/
3
ππ* of 8.7 cm
−1
in 5ACyd and 10.2 cm
−1
in 5AdCyd, respectively. Subsequently, the T
1
system will approach the nearby T
1
/S
0
crossing point
3
ππ*/S
0
driving it back to the S
0
state. Given the
3
ππ*/S
0
crossing point located above the T
1
minimum and the small T
1
/S
0
SOC,
i.e.
, 8.4 kcal mol
−1
and 2.1 cm
−1
in 5ACyd and 6.8 kcal mol
−1
and 1.9 cm
−1
in 5AdCyd, respectively, the slow T
1
→ S
0
would trap the system in the T
1
state for a while. The present work could contribute to understanding the mechanistic photophysics and photochemistry of similar aza-nucleosides and their derivatives.
The excited state properties and deactivation pathways of two DNA methylation inhibitors,
i.e.
, 5-azac |
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ISSN: | 1463-9076 1463-9084 |
DOI: | 10.1039/d3cp03628f |