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Photoconversion of β-Lapachone to α-Lapachone Via a Protonation Assisted Singlet Excited State Pathway in Aqueous Solution: A Time-Resolved Spectroscopic Study

xinlan's picture

xinlan - Posted on 18 September 2015

Project Description: 

femtosecond and nanosecond transient absorption (fs-TA and ns-TA) and nanosecond time-resolved resonance Raman (ns-TR3) spectroscopic methods to investigate the early events taking place for β-LA after photoexcitation in aqueous solutions. As far as we know, this is the first time that fs-TA, ns-TA and ns-TR3 experiments have been performed on β-LA in different acetonitrile (MeCN):H2O mixture solutions in order to investigate the role of water on the excited states, intermediates and dynamics of reactive intermediates that are involved in the photochemistry of β-LA. To help determine the geometries and vibrational spectra of the intermediate species and assignments of the experimental vibrational bands, density functional theory (DFT) calculations were done using the B3LYP methods with a 6-311G** basis set for all of the species examined here. The structure and properties of the triplet state of β-LA (β-3LA) is also briefly discussed. In order to distinguish the important role of the pyran ring in the photochemistry, the photoreaction of the parent compound 1,2-naphthoquinone (NQ) that does not contain a pyran ring (see Scheme 1 below) was also studied by time-resolved spectroscopy methods in both MeCN and aqueous solutions and compared to the results found for β-LA here. Our time-resolved spectroscopy results indicate that a photoinduced protonation of the carbonyl group at β position takes place for the singlet excited state of β-LA with the assistance of water in aqueous solutions. This protonation initiates a series of processes that lead to the conversion of some β-LA to α-LA in water rich solutions and acidic aqueous solutions. This photoinduced protonation reaction provides insight into the role of water playing in the cytotoxicity and phototoxicity of β-LA in biological systems and its potential use in photodynamic therapy applications.

Research Project Details
Project Duration: 
10/2013-08/2016
Project Significance: 
β-lapachone (β-LA) is an ortho-naphthoquinone obtained from the heartwood of Tabebuia avellanedae which is mainly found in Brazil. β-LA has been extensively studied due to its anti-cancer properties. β-LA has been found to inhibit the growth of sarcoma tumors in mice, to be cytotoxic to leukemia cells and human cancers such as breast, colon, prostate and lung. The mechanism of the observed cytotoxicity in cancer cells appears to be due to NAD(P)H quinine oxidoreductase-1 performing a two-electron reduction of β-LA to produce its hydroquinone, that may then generate reactive oxygen species to induce DNA damage that can lead to cell death.Therefore, there has been some research effort conducted on the photoreactions of β-LA.
Results Achieved: 
The photophysical and photochemical reaction of β-lapachone were studied using femtosecond transient absorption, nanosecond transient absorption, and nanosecond time-resolved resonance Raman spectroscopy techniques and density functional theory calculations. In acetonitrile, β-lapachone underwent an efficient intersystem crossing to form the triplet state of β-lapachone. However, in water-rich solutions, the singlet state of β-lapachone was predominantly quenched by the photoinduced protonation of the carbonyl group at the β position (O9). After protonation, a series of fast reaction steps occurred to eventually generate the triplet state α-lapachone intermediate. This triplet state of α-lapachone then underwent intersystem crossing to produce the ground singlet state of α-lapachone as the final product. 1,2-naphthoquinone is examined in acetonitrile and water aqueous solutions in order to elucidate the important roles of water and the pyran ring playing during the photoconversion from β-lapachone to α-lapachone. β-lapachone can be also converted to -lapachone on the ground state when a strong acid is added to an aqueous solution. Our investigation indicates that β-lapachone can be converted to -lapachone by photoconversion in aqueous solutions by a protonation assisted singlet excited state reaction or by an acid assisted ground state reaction.