TY - JOUR

T1 - Triplet state generation by furocoumarins revisited

T2 - A combined QSPR/DFT approach

AU - Буглак, Андрей Андреевич

AU - Кононов, Алексей Игоревич

N1 - Publisher Copyright: © 2018 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

PY - 2018

Y1 - 2018

N2 - Furocoumarins (psoralens and angelicins) are often used for the photo-treatment of psoriasis, vitiligo, atopic dermatitis and other dermatological pathologies. The mechanism of furocoumarin action in vivo is as follows: furocoumarin enters the cells and intercalates between DNA base pairs. Upon exposure to UVA, furocoumarin absorbs photons, becomes chemically activated, and covalently binds to DNA base pairs, forming cross-links and cyclobutane type adducts with DNA. The triplet state formation by furocoumarins is a key process, which leads not only to covalent binding to DNA, but also to the generation of reactive oxygen species and photooxidation reactions. Our goal was to develop a quantitative structure-property relationship (QSPR) model for the fast virtual screening and prediction of the efficiency of triplet state generation by furocoumarins. We performed QSPR analysis of 26 furocoumarin compounds (including widely known 8-methoxypsoralen and 5-methoxypsoralen) for their ability to form triplet excited states. Quantum-chemical descriptors were calculated using the HF, B3LYP and PBE0 methods. The ability of furocoumarins to generate triplet states was found to be significantly correlated with the T1 triplet state energy (R2 = 0.627) and the Jhetv descriptor. The best QSPR model "structure-triplet state generation" possesses high internal stability (q2 = 0.865) and a high predicting ability for the test set (pred-R2 = 0.897). The evaluation of reactive oxygen species generation feasibility using Density Functional Theory (DFT) was also performed. We hope that the QSPR model developed in this study will be useful in the development of new synthetic psoralens and angelicins for medicinal purposes.

AB - Furocoumarins (psoralens and angelicins) are often used for the photo-treatment of psoriasis, vitiligo, atopic dermatitis and other dermatological pathologies. The mechanism of furocoumarin action in vivo is as follows: furocoumarin enters the cells and intercalates between DNA base pairs. Upon exposure to UVA, furocoumarin absorbs photons, becomes chemically activated, and covalently binds to DNA base pairs, forming cross-links and cyclobutane type adducts with DNA. The triplet state formation by furocoumarins is a key process, which leads not only to covalent binding to DNA, but also to the generation of reactive oxygen species and photooxidation reactions. Our goal was to develop a quantitative structure-property relationship (QSPR) model for the fast virtual screening and prediction of the efficiency of triplet state generation by furocoumarins. We performed QSPR analysis of 26 furocoumarin compounds (including widely known 8-methoxypsoralen and 5-methoxypsoralen) for their ability to form triplet excited states. Quantum-chemical descriptors were calculated using the HF, B3LYP and PBE0 methods. The ability of furocoumarins to generate triplet states was found to be significantly correlated with the T1 triplet state energy (R2 = 0.627) and the Jhetv descriptor. The best QSPR model "structure-triplet state generation" possesses high internal stability (q2 = 0.865) and a high predicting ability for the test set (pred-R2 = 0.897). The evaluation of reactive oxygen species generation feasibility using Density Functional Theory (DFT) was also performed. We hope that the QSPR model developed in this study will be useful in the development of new synthetic psoralens and angelicins for medicinal purposes.

KW - AMOTOSALEN

KW - DNA

KW - ILLUMINATION

KW - INACTIVATION

KW - PHOTOCHEMOTHERAPY

KW - PLASMA

KW - PSORALEN

KW - SINGLET OXYGEN

KW - ULTRAVIOLET

KW - VIRUS

UR - http://www.scopus.com/inward/record.url?scp=85051956864&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/triplet-state-generation-furocoumarins-revisited-combined-qsprdft-approach

U2 - 10.1039/C8NJ03002B

DO - 10.1039/C8NJ03002B

M3 - Article

AN - SCOPUS:85051956864

VL - 42

SP - 14424

EP - 14432

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

IS - 17

ER -