Photosensitizing properties of triplet furano and pyrano-1,2-naphthoquinones

Journal of Photochemistry and Photobiology A: Chemistry 276 (2013) 16–30

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Photosensitizing properties of triplet furano and pyrano-1,2-naphthoquinones Nanci C. de Lucas a,∗ , Carolina P. Ruis a , Rodolfo I. Teixeira a , Luisa L. Marc¸al a , Simon J. Garden a , Rodrigo J. Corrêa a , Sabrina Ferreira a , José Carlos Netto-Ferreira b , Vitor F. Ferreira c a

Instituto de Química, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, Cidade Universitária, 21949-900 Rio de Janeiro, RJ, Brazil Departamento de Química, Universidade Federal Rural do Rio de Janeiro, BR 465 km 7, 23970-000 Seropédica, RJ, Brazil c Departamento de Química Orgânica, Instituto de Química CEG, Universidade Federal Fluminense, Campus do Valonguinho, 24020-150 Niterói, RJ, Brazil b

a r t i c l e

i n f o

Article history: Received 25 August 2013 Received in revised form 24 October 2013 Accepted 21 November 2013 Available online 1 December 2013 Keywords: Photosensitizer Triplet state 1,2-Naphthoquinone TDDFT Singlet oxygen Proton coupled electron transfer

a b s t r a c t The absorption spectra for both families of naphthoquinones reveal a solvatochromic red shift in polar solvents which is consistent with the ␲,␲* character of the S0 → S1 electronic transition in all cases. The photochemical reactivity of a series of substituted furano- and pyrano-1,2-naphthoquinones has been examined by laser flash photolysis. Excitation ( = 355 nm or 266 nm) of degassed solutions of the quinones 1a–f and 2a–f, in acetonitrile, resulted in the formation of their corresponding triplet excited state. Addition of hydrogen donors, such as 2-propanol, toluene and methylcyclohexane led to the formation of new transients, which were assigned to the corresponding ketyl radicals derived from the hydrogen abstraction reaction by the corresponding triplets. The low values (kq ∼ 105 L mol−1 s−1 ) observed for the hydrogen abstraction rate constants for the naphthoquinones using 2-propanol as the quencher led us to conclude that the triplet excited state has ␲␲* character. The triplet excited state of these naphthoquinones was efficiently quenched by 4-methoxyphenol and N-acetyl l-tryptophan methyl ester (kq ∼ 109 L mol−1 s−1 ). In all cases a new transient was formed in the quenching process, which was assigned to the corresponding radical pair resulting from an initial electron transfer from the quencher to the excited quinone, followed by a fast proton transfer. The quantum efficiency of singlet oxygen (1 O2 ) formation from the naphthoquinones was determined by employing time-resolved near-IR emission studies upon laser excitation and revealed large values in all cases, which are fully in accord with the ␲␲* character of these triplets in acetonitrile. Theoretical calculations (TD) DFT were used to calculate UV–vis spectra and to investigate the nature of the transition of max as well as to investigate the structure and reactivity of the first triplet state. The calculated triplet energies are compatible with the experimental findings and the calculated hydrogen abstraction from phenol by T1 quinones indicates a PCET mechanism. © 2013 Elsevier B.V. All rights reserved.

1. Introduction Naphthoquinones have been extensively studied due to their numerous biological and pharmacological activities [1–18]. The mechanism of action of these quinones is related to redox cycling, which can lead to the formation of reactive oxygen species that can damage cellular macromolecules [19–21]. ␤-Lapachone, a pyrano-ortho-naphthoquinone, is a natural product that is readily extracted from the heartwood of Tabebuia avellanedae, which is found mainly in South America [22–24]. It possesses various pharmacological activities and has long been recognized for its anti-cancer properties [25–29]. The cytotoxicity of

∗ Corresponding author. Tel.: +55 21 2562 72 78. E-mail address: [email protected] (N.C. de Lucas). 1010-6030/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jphotochem.2013.11.010

this quinone to many human cancer cell lines has been widely studied [30–34] and its activity has been associated with the inhibition of DNA repair enzymes [35], inhibition or activation of DNA topoisomerase I [27,33], induction of topoisomerase IIa-mediated DNA breaks [36], and inhibition of poly(ADP-ribose) polymerase-1 [37]. Oxidative damage to biological systems, either accidental or intentional, is a major cause of cell death [38]. In particular, apoptotic or necrotic signalling pathways to cell death can be induced by the combined use of a photo-activated drug, called the photosensitizer, and per se harmless visible light. This process involves the generation of reactive oxygen species (ROS) capable of inflicting damage to susceptible cell components such as proteins [39,40], membrane lipids [41], and nucleic acids [42]. Several mechanisms account for the reactions of molecules in photosensitized processes [43,44]. The photosensitized reactions

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17

In the present investigation we detail results of laser flash photolysis studies of the reactivity of pyrano- and furano-1,2naphthoquinones towards hydrogen and electron donors, as well as to N-acetyl tryptophan methyl ester, a model compound of a biological substrate, as well as their ability in efficiently transfer energy so as to result in the formation of singlet oxygen, O2 (1 g ) (Scheme 1). 2. Materials and methods 2.1. General Scheme 1.

have been classified into two types. In the first case, type I mechanisms may involve H-abstraction or electron transfer. These processes result in the formation of radical species that can promote biomolecular oxidation. In the second case, the type II mechanism, energy is transferred to molecular oxygen resulting in singlet oxygen formation. The singlet oxygen then reacts with biological substrates in oxidative processes [45]. With respect to proteins, the aromatic amino acids, tryptophan (TrpH) and tyrosine (TyrOH), are readily oxidized [46,47]. Therefore there has been considerable interest in the study of the photo-oxidation reactions of TrpH and TyrOH with photosensitizers. Laser excitation of ␤-lapachone, in acetonitrile, gives rise to the triplet excited state via ultrafast S–T intersystem crossing (kISC ∼ 1011 s−1 ) [48], The T1 –Tn absorption spectrum reveals a sharp maximum at 380 nm and a broad band in the region from 500 to 700 nm [49]. The lack of solvent effects observed in the quenching rate constants of the triplet ␤-lapachone by 2-propanol and 1, 4-cyclohexadiene suggests that its lowest energy triplet excited state has ␲␲* character. On the other hand, the lowest lying triplet state of other non-substituted naphthoquinones have ␲,␲* character in polar solvents and n,␲* in non-polar solvents [50]. This difference in configuration is the consequence of a small energy separation between the n,␲* and ␲,␲* triplet levels [51]. 1,2Naphthoquinone is non-phosphorescent but a number of other aryl-1,2-diketones are. Due to the phosphorescence of the latter systems the triplet energy can be estimated to be less than 50 kcal/mol and greater than 30 kcal/mol [52]. Recently, laser flash photolysis experiments on ␤-lapachone and nor-␤-lapachone have shown that these quinones are able to act as photosensitizers for the one-electron oxidation of the amino acids l-tryptophan, l-tyrosine and l-cysteine. The quantum efficiency of singlet oxygen formation from these quinones was also determined and revealed large values in all cases (˚ = 0.6) [49,53,54]. In a recent study we characterized the photobehaviour of condensed 1,4-naphthoquinone systems, analogous with the furano- and pyrano-1,2-naphthoquinones employed in this study and found them to be excellent singlet oxygen sensitizers [55]. tetrahydropyranoand dihydrofurano-1,2The naphthoquinone compounds shown in Scheme 1 are synthetic products that have shown great potential in pharmacological applications and posses structures similar to the natural ␤-lapachone and nor-␤-lapachone [2,56,57]. There is considerable interest in the photochemistry of 1,2-naphthoquinones and studies have focused on both the fundamental aspects and the biological applications [52,53,58–60]. However, the influence of fused ring size and the substituents on the photobehaviour of condensed systems, such as pyrano- and furano-1,2-naphthoquinones has been little explored. In principle, the differences in ring strain might have an influence on the excited state properties due to changes in geometrical parameters and the electronic distribution.

Solvents, acetonitrile, 2-propanol, chlorobenzene, cyclohexane, methylcyclohexane (all spectroscopic grade) and deuterated water, as well as the reagents perinaphthenone, ␤-carotene, indole, ltryptophan methyl ester and 4-methoxyphenol, were all purchased from Sigma–Aldrich and used as received. Water was milli-Q grade. N-Acetyl l-tryptophan methyl ester (NATME) was synthesized by a standard procedure (mp = 150–152 ◦ C, Lit = 152 ◦ C; yield: 88%) [61]. Naphthoquinone derivatives 1a–f and 2a–f were prepared as described in the literature and spectroscopic and spectrometric properties are fully in accord with the structures proposed [2,56,57]. 2.2. UV–visible spectra UV–vis spectrum of the quinones 1a–f and 2a–f were recorded using a Shimatzu model UV-2450 in either acetonitrile or cyclohexane. 2.3. Laser flash photolysis The laser flash photolysis experiments were carried out on a LuzChem Instrument model mLFP122. Samples were contained in a 10 mm × 10 mm cell made from Suprasil tubing and were deaerated by bubbling with argon for about 20 min. The samples were irradiated with the third ( = 355 nm) or fourth ( = 266 nm) harmonic of a Nd/YAG Surelite laser. All laser flash photolysis experiments were performed in acetonitrile solution, unless otherwise indicated in the text. The concentration of naphthoquinones was adjusted to yield an absorbance of ∼0.3 at the excitation wavelength (355 or 266 nm). Stock solutions of quenchers were prepared so that it was only necessary to add microliter volumes to the sample cell in order to obtain appropriate concentrations of the quencher. The rate constants for the reaction of triplet naphthoquinones with the different quenchers employed in this work were obtained from Stern–Volmer plots, following Eq. (1). kobs = ko + kq [Q ]

(1)

where ko is the triplet decay rate constant in the absence of quencher; kq is the triplet decay rate constant in the presence of the quencher and [Q] is the quencher concentration in mol L−1 . The trace at 650 nm was used to determine the quenching rate constants in order to avoid the influence of the ketyl radical decay on kinetic trace corresponding to the triplet excited state. It is important to note that in the quenching experiments samples were excited at 355 nm, since at this wavelength the only absorbing species is the naphthoquinone. 2.4. Singlet oxygen measurements The quantum efficiency of singlet oxygen (1 O2 ) formation was determined using a spectrofluorometer (FS920 Edinburgh Instruments) with a TMS300 monochromator. The detection system was equipped with a NIR Hamamatsu model H1033-45 photomultiplier. The excitation source (355 nm) was provided by a CryLas

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Nd-YAG HP 355-50 laser (pulse width of 1.0 ns and energy <150 ␮J). Singlet oxygen formation was observed by monitoring the phosphorescence at 1270 nm upon laser excitation of optically matched solutions (A = 0.3 in air–saturated acetonitrile) of the naphthoquinones relative to a standard solution of perinaphthenone, which shows singlet oxygen quantum yield of 1.0 [62]. The quantum yield for singlet oxygen formation was determined from the slope of the plots of signal intensity at zero time at 1270 nm versus laser light intensity, using a set of neutral density filters, employing Eq. (2), where Isample is the emission intensity recorded for the sample, IPER is the perinaphthenone emission intensity, used as standard, and ˚PER is the quantum yield of singlet oxygen formation from perinaphthenone. ˚sample =

Isample IPER

× ˚PER

0.3

0.2

1

0.8

absorbance

18

0.1

0.6 0 300

350

400

450

500

550

wavelength, nm

0.4

(2) 0.2

2.5. Theoretical calculations

3. Results and discussion 3.1. UV–vis spectrum The absorption spectrum for the 1,2-naphthoquinones employed in this study clearly reveals a difference between the tetrahydropyrano- (1a–f) and the dihydrofuranonaphthoquinones (2a–f). Fig. 1 shows the spectra for 1a and 2a in cyclohexane and acetonitrile. A solvatochromic red shift, for the band around 400 nm, similar to that observed for ␤-lapachone [55], is also observed when the compounds are dissolved in acetonitrile in comparison to the spectra in cyclohexane for both pyrano- and furano- naphthoquinones, which is consistent with the ␲,␲* character of the S0 → S1 electronic transition. This behaviour is analogous to the 1,4-naphthoquinones recently reported by us [55]. Additionally, a shoulder is readily visible on the spectra of 1a and 2a above 500 nm in acetonitrile whereas in cyclohexane a shoulder is less obvious but extended absorption above 500 nm is readily discernible. 1,2-Naphthoquinone reveals a small absorption with maximum at 537 nm which was assigned to the n,␲* transition [52].

0 200

300

400

500

wavelength, nm 0.4

0.32

1

0.24

0.16

0.8

0.08

absorbance

Energy and geometry calculations were performed at (U)B3LYP/6-311++G**//(U)B3LYP/6-31G* computational level for all quinone-phenol structures [63–65]. The calculations were performed using Spartan’10 (initial conformational analysis) and Gaussian 09 [66,67]. All the reported data derive from the results obtained with Gaussian 09. The gas phase geometries were optimized using standard techniques [68,69], and vibrational analysis was performed to confirm that the geometries were true minima on the potential energy surface, as shown by the absence of imaginary frequencies, or saddle points that corresponded to a transition state having a single imaginary vibration that corresponded to vibration along the forming/breaking bonds. The DFT method was used as it reasonably estimates spin contamination. Values for S2  were typically consistent with two unpaired electrons for all triplets. Solvation energies were optimized by use of IEF-PCM as implemented in Gaussian 09 [70–72]. UV–vis spectra of the quinones were calculated by TD-DFT using the same functional (f) that was used to calculate the solvent optimized geometry (IEFPCM) of the ground state, where f = B3LYP, CAM-B3LYP [73], and PBE0 [74,75] (in all cases n states = 20). Atomic (ChelpG) charges were calculated from the electrostatic potential as implemented in Gaussian 09 for both gas phase and solvent optimized structures [76].

0.6 0 300

350

400

450

500

550

wavelength, nm

0.4

0.2

0 200

300

400

500

wavelength, nm Fig. 1. Absorbance spectra for 1a (top) and 2a (bottom) (3 × 10−5 mol L−1 ) in acetonitrile (- - -) and cyclohexane ( ). Inset: long-wavelength region (10−4 mol L−1 ).

3.2. Singlet oxygen formation Singlet oxygen can be formed through an energy transfer process from a suitable donor. A tiny fraction of 1 O2 molecules undergoes radiative decay, thereby emitting a photon in the near infrared (NIR). This extremely weak phosphorescence, centered at 1270 nm, provides the means for the most direct and unambiguous method for 1 O2 detection. A representative decay for the singlet oxygen phosphorescence generated by energy transfer from 2a is shown in Fig. 2. Linear plots for the singlet oxygen phosphorescence intensity versus energy dependence were obtained for perinaphthenone (standard) and the respective naphthoquinone (inset Fig. 2). From the slopes of these plots one could calculate the quantum yield of singlet oxygen (1 O2 ) formation and in all cases a value close to 0.7 was found (Table 1). Values of 0.6 have been reported for the analogous ␤-lapachone and nor-␤-lapachone [54]. The quantum yield for singlet oxygen formation for an

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19

0.025 Time after the laser pulse (µs)

1.8 6.4 17.5 32.6

0.02

A

0.015

0.01

0.005

0 300

350

400

450

500

550

600

650

700

, nm Fig. 3. LFP spectra observed for 1a in nitrogen saturated acetonitrile (exc = 355 nm). Fig. 2. Decay for the singlet oxygen phosphorescence emission generated upon excitation (exc = 355 nm) of a sample of 1c in acetonitrile monitored at 1270 nm. Inset: representative plots for singlet oxygen phosphorescence emission versus light intensity for solutions of perinaphthenone (䊉) (standard for comparison), and 1c ().

0.008 Time after the laser pulse (µs)

0.007 Table 1 The quantum efficiency of singlet oxygen (1 O2 ) formation by the 1,2naphthoquinones (Scheme 1) in air-saturated acetonitrile (exc = 355 nm). Furano-1,2-naphthoquinones

␤-Lapachonea 1a 1b 1c 1d 1e 1f

nor-␤-Lapachonea 2a 2b 2c 2d 2e 2f

0.6 0.74 0.68 0.76 0.76 0.77 0.70

0.005 0.6 0.51 – 0.77 0.77 0.76 0.72

Error ± 10%. a Ref. [54].

isomeric series of 1,4-naphthoquinones was found to be about 15% greater than the values obtained in the present study for the 1,2naphthoquinones [55]. A similar behaviour can be found when one compares the quantum yield of singlet oxygen formation between ␤-lapachone, a pyrano-1,2-naphthoquinone [54] and ␣-lapachone, a pyrano-1,4-naphthoquinone [53]. The large values for the quantum yield are in accord with the requirement for a ␲␲* triplet for highly efficient singlet oxygen formation [54]. 3.3. Laser flash photolysis Laser flash photolysis of deoxygenated acetonitrile solutions for all naphthoquinones employed in this work led to the formation of a detectable transient with sharp band absorptions at 300 and 380 nm and a broad band at 650 nm with a lifetime of 5 ␮s. Figs. 3 and 4 show representative spectra for the transient obtained after laser excitation of 1a and 2a, respectively. A similar transient absorption spectrum was obtained for ␤-lapachone and derivatives, as described in the literature [49,54,60]. Furthermore there is no difference in the T–T absorption spectra for the pyrano-1,2- and furano-1,2-naphthoquinones. Similar LFP spectra were also observed in dichloromethane and chlorobenzene. These transients were quenched by oxygen in a diffusion controlled process, whilst in the presence of ␤-carotene, a frequently used triplet state quencher due to its low triplet energy (19 kcal/mol), the formation of a 520 nm band due to the

A

Pyrano-1,2-naphthoquinones

4.0 14.5 30.2 78.1

0.006

0.004 0.003 0.002 0.001 0 300

350

400

450

500

550

600

650

700

, nm Fig. 4. LFP spectra observed for 2a in nitrogen saturated acetonitrile (exc = 355 nm).

␤-carotene triplet was readily observed [77]. Fig. 5 shows the spectra obtained for 1f in a saturated solution of ␤-carotene and the inset shows the kinetic trace (growth and decay) for the triplet of ␤-carotene at 520 nm. Further, the triplets of 1a and 2a were not quenched by benzil (T1 energy = 54.3 kcal/mol) or 1,3-cyclohexadiene (T1 energy = 52.4 kcal/mol) [77] in acetonitrile. However these triples were quenched by (E)stilbene (T1 energy = 49.3 kcal/mol) [77] with a rate constant of 3.50(±0.12) × 108 and 5.07(±0.24) × 108 L mol−1 s−1 , for 1a and 2a, respectively. Therefore the triplet energies of the naphthoquinones of the present study should be smaller than the triplet energy of (E)-stilbene, consistent with literature precedents [52,54] and in line with the theoretical results of this study. The transient absorption spectra for the naphthoquinones in 2-propanol, toluene and methylcyclohexane are quite different from that observed in acetonitrile. These solvents are known to be good hydrogen donors and the spectra recorded after a long time delay, when the triplet has completely disappeared, show a sharp band with maximum at 380 nm, as shown in Fig. 6 for 1a in methylcyclohexane. This absorption spectrum can be assigned to

20

N.C. de Lucas et al. / Journal of Photochemistry and Photobiology A: Chemistry 276 (2013) 16–30 0.015

Time after the laser pulse (µs)

0.013

0.5

0.03

A

2.5 A

0.03

0.01 0.009

0.005

0.004

0.025

0

0.02

-0.005

0

0.02

0

2

4

6

8

10

Time, µs

0

50

100

150

200

250

0.01

A

A

Time, µs

0.015

Time after the laser pulse (µs)

6.6 41 80 163

0.01

0

0.005 -0.01 300

400

500

600

700

800

, nm

Fig. 5. LFP spectra observed for 1f in ␤-carotene saturated acetonitrile solution. Inset: kinetic trace at 520 nm.

the ketyl radical derived from 1a. The time profile for the decay monitored at 380 nm in methylcyclohexane and recorded 50 ms after the laser pulse clearly shows that this new transient has a longer lifetime when compared to the triplet state (Fig. 6, inset). The quenching plots for representative triplet naphthoquinones by 2-propanol in acetonitrile show rate constants in the range of 1.0–2.5 × 105 L mol−1 s−1 (Table 2). Similar values were obtained for ␤-lapachone and nor-␤-lapachone, for which the triplet was assigned ␲␲* character [54]. Ketyl radicals are known to be excellent electron donors with methyl viologen, MV2+ , being the most commonly used acceptor (Eq. (3)) [78]. The methyl viologen radical cation formed through electron transfer from a ketyl radical has strong absorption bands at 398 and 603 nm and is easily observed in LFP experiments [78,79]. LFP experiments performed with 1a in 2-propanol, in the presence of methyl viologen, led to the formation of the methyl viologen radical cation (Fig. 7). Similar behaviour was also observed for 2a.

0 300

350

400

450

500

550

600

650

700

, nm Fig. 6. Transient absorption spectra observed upon laser excitation (355 nm) of 1a in nitrogen saturated methylcyclohexane. Inset: kinetic trace monitored at 380 nm.

semiquinone–organoradical pair. When N-acetyl l-tryptophan methyl ester was employed as a quencher, the l-tryptophanyl radical, which shows a broad absorption in the 450–550 nm region, was easily observed [60,82,83]. Fig. 8 shows the transient absorption spectra recorded upon laser excitation of an acetonitrile solution of 2a in the presence of 2.3 × 10−4 M N-acetyl l-tryptophan methyl ester. The inset in Fig. 8 shows the kinetic trace recorded at 500 nm. The transient absorption spectra obtained are similar to those obtained by quenching the triplet quinones employed in the present study by indole (not shown). The strong absorption band observed at 370 nm can be attributed to the corresponding semiquinone radical derived from 2a. When 4-methoxyphenol was employed as a quencher, the 4methoxyphenoxyl radical was also observed [84]. Fig. 9 shows the

(3) 4-Methoxyphenol and N-acetyl l-tryptophan methyl ester have been employed as quenchers for the triplet excited state of the naphthoquinones 1a–f and 2a–f, in acetonitrile. In all cases, linear quenching plots following Eq. (1) were obtained and the resulting quenching rate constants (kq ) are in the order of 2 × 109 L mol−1 s−1 , as shown in Table 2. For comparison, values of 4.8 × 109 and 4.5 × 109 L mol−1 s−1 were obtained for the quenching rate constant of ␤-lapachone and nor-␤-lapachone triplet with l-tryptophan methyl ester, respectively [54]. The large values for the quenching rate constants of 1a–f and 2a–f by 4-methoxyphenol and N-acetyl l-tryptophan methyl ester indicate that in both cases the mechanism involved in the hydrogen transfer process is quite similar and must involve a coupled proton electron transfer as demonstrated previously for other ortho-quinones [49,54,80,81]. The proton coupled electron transfer mechanism ultimately results in the experimental observation of the

transient absorption spectrum recorded upon laser excitation of an acetonitrile solution of 2e in the presence of 8.2 × 10−4 M 4methoxyphenol. The shoulder at 410 nm on the strong absorption band at 370 nm (due to the semiquinone radical derived from 2e) can be attributed to the 4-methoxyphenoxyl radical. The photobleaching observed at 450 nm can be attributed to absorption by the ground state of 2e. To further investigate the proton coupled electron transfer mechanism, some experiments involving an isotope effect were performed. The quenching of the triplet quinone 1f by NATME or 4-methoxyphenol was chosen for this study. The isotope effect was taken into account by comparing the reactivity of triplet 1f when CH3 CN:D2 O (9:1, V/V) and CH3 CN:H2 O (9:1, V/V) were employed as solvents (Table 2). Isotope effects of 1.42 and 1.56 were observed for NATME and 4-methoxyphenol, respectively. These values indicate that stretching of the O H bond in the phenol and N H bond in NATME are not important in the transition state, strongly

N.C. de Lucas et al. / Journal of Photochemistry and Photobiology A: Chemistry 276 (2013) 16–30

0.25

21

Time after the laser pulse (µs)

0.25

2.96 9.08 19.2 34.6

0.2

0.2 Time after the laser pulse (µs)

6.0 29.6 90.4 172.0

0.15

A

A

0.15

0.1

0.1

0.05

0.05

0

0

300

350

400

450

500

550

600

650

700

300

350

400

450

, nm

indicating that a proton coupled electron transfer mechanism is operating [79]. 3.4. Theoretical calculations DFT calculations were used to investigate the nature of the T1 state and the hydrogen abstraction reaction from phenol by pyranoand furano-1,2-naphthoquinones (1 = NQP and 2 = NQF). The structures of the 1,2-quinones were simplified by removing the exocyclic phenyl group as this is sufficiently remote so as to have minimal electronic and steric influence as seen from the experimental results. Experimentally, the ␲–␲* nature of the principal absorption in the visible part of the UV–vis spectrum was characterized by a bathochromic shift in the S0 → S1 transition on changing the solvent 0.03

0.02

650

700

A

Fig. 9. LFP spectra observed for 2e in the presence of 8.2 × 10−4 M 4-methoxyphenol in ACN (exc = 355 nm).

from cyclohexane to acetonitrile. Therefore in order to simulate the experimental spectra, the solvent optimized structures (IEF-PCM) of NQF and NQP were used to calculate UV–vis spectra. Calculation of the UV–vis spectra (TD-DFT B3LYP, CAM-B3LYP, and PBE0) using solvent optimized structures gave a faithful reproduction of the experimentally observed spectra and the solvatochromic shift when a minimal basis set polarized with d orbitals and augmented with diffuse functions (6-31+Gd) was used [85,86]. The solvent optimized calculations of max for the model structures NQP (1) and NQF (2) are given in Table 3 and examples of the calculated spectra are reproduced in Fig. 10. The CAM-B3LYP method gave the best results for prediction of the principal longer wavelength excitation whilst the use of the PBE0 or B3LYP functionals gave the better results for prediction of the shorter wavelength excitations and the “forbidden” n–␲* transition. The results are in accord with the finding that CAM-B3LYP has been found to be well suited for the calculation of the lowest energy, very delocalized, ␲* excited states [87]. Despite the success of PBE0 for the calculation of UV–vis spectra [86–88], the respective calculation for acetonitrile or cyclohexane solvated NQP or NQF gave 30–40 nm red shifted Table 2 Experimental quenching rate constants (kq ) of 1,2-naphthoquinone triplets in acetonitrile.

0

-0.01

0.04

0

10

20

30

40

50

1,2-Naphthoquinone

Time, µs

A

600

0.01

0.05

Time after the laser pulse (µs)

4.0 19 42 73

0.02

0.01

350

400

450

500

550

600

kq /L mol−1 s−1 2-propanol

0.03

0 300

550

, nm

Fig. 7. LFP spectra observed for 1a and excess methylviologen, in 2-propanol solution.

0.06

500

650

700

, nm

1a 1b 1c 1d 1e 1f

1.0 × 105 1.4 × 105 1.8 × 105 – –

2a 2b 2c 2d 2e 2f

2.4 × 105 1.8 × 105 2.4 × 105 2.2 × 105 – –

a

Fig. 8. LFP spectra observed for 2a in the presence of 2.8 × 10−4 M N-acetyl tryptophan methyl ester in ACN (exc = 355 nm). Inset: Kinetic trace at 500 nm.

ACN:H2 O 9:1. ACN:D2 O 9:1. Error ± 10% b

NATME

4-MeO phenol

2.0 × 109 2.3 × 109 2.0 × 109 2.1 × 109 1.5 × 109 2.4 × 109 2.7 × 109 a 1.9 × 109 b 2.7 × 109 1.1 × 109 1.3 × 109 1.7 × 109 2.5 × 109 2.4 × 109

5.1 × 109 3.2 × 109 2.2 × 109 1.9 × 109 1.9 × 109 4.3 × 109 3.2 × 109 a 2.0 × 109 b 2.2 × 109 1.5 × 109 1.8 × 109 1.6 × 109 1.7 × 109 2.2 × 109

22

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Table 3 Observed values of max . and calculated values of max .

NQP (1) cy-C6 H12 NQP (1) ACN NQF (2) cy-C6 H12 NQF (2) ACN a b c d e f g

max obsd.a (nm)

max calc.b (nm)

max calc.c (nm)

max calc.d (nm)

max calc.e (nm)

max calc.f (nm)

max calc.g (nm)

407 253 211 424 260 210 420 257 210 438 255 211

442 255

458 261 213 483 262 214 473 271 218 497 270 219

459 263 214 484 264 216 475 273 218 498 272 220

391 233 194 411 233 195 404 237 196 423 237 196

393 235 196 412 235 196 405 239 198 424 239 197

438 253 209 461 253 207 455 262 211 476 262 212

460 255 457 265 475 267

Experimental values taken from the UV–vis spectra of 1a and 2a. B3LYP/6-31G*. B3LYP/6-31+G*. B3LYP/6-311++G**//6-31+G*. CAM-B3LYP/6-31+G*. CAM-B3LYP/6-311++G**//6-31+G*. PBE1PBE/6-31+G*. For all calculations n states = 20.

Fig. 10. Calculated (TD CAM-B3LYP/6-311++G**//6-31+G*, n states = 20) UV–vis spectra (150-600 nm) revealing a bathosolvatochromic effect in acetonitrile relative to cyclohexane for NQP and NQF and the bathochromic shift of max for NQF relative to NQP.

deviations of max . However, the maxima of the higher energy, shorter wavelength, excitations were in excellent agreement with the experimental results. A closer look at the low energy side of the visible spectra (see insets of Fig. 1) reveals the presence of shoulders and extended absorption above 500 nm in both acetonitrile and cyclohexane. 1,2Naphthoquinone, a simpler analogue of NQP and NQF, reveals a small absorption with max 537 nm which has been attributed to the n → ␲* transition [52]. This feature of the spectra for 1a and 2a (ε of the order 100 L mol−1 cm−1 ) can therefore be attributed to the forbidden n → ␲* transition. In Table 4, a comparison of the calculated values of max for the forbidden first excited state is given. The calculated first excited state transition has contributions from various pairs of canonical molecular orbitals. However, a single pair of molecular orbitals corresponding to the HOMO-1 → LUMO transition had the most significant CI coefficient (greater than 96% contribution) in the case of the B3LYP and PBE0 calculations. Whereas the CAM-B3LYP calculation was found to be composed of a mixture of significant pairs of canonical molecular orbitals for which the principal positive CI coefficient consisted of a HOMO-1 → LUMO transition (92% contribution). The calculated oscillator strengths for these transitions

Table 4 Calculated values (IEFPCM TDDFT) of max for the forbidden first excited state. Structure/solvent

max calc.a (nm)

max calc.b (nm)

max calc.c (nm)

NQP (1) cy-C6 H12 NQP (1) ACN NQF (2) cy-C6 H12 NQF (2) ACN

535 510 537 509

469 451 467 447

522 500 523 498

a b c

B3LYP/6-31+G*. CAM-B3LYP/6-31+G*. PBE1PBE/6-31+G*.

were all zero. In the case of the CAM-B3LYP calculations, a natural transition orbital analysis [89] for the first excited state confirmed the n → ␲* nature of this transition ( > 0.98, see Fig. 11). Notably, the B3LYP and the PBE0 calculations give a much closer estimate of max for the n → ␲* transition in comparison to CAMB3LYP (based upon max for 1,2-naphthoquinone, 537 nm) when the TDDFT calculations are based upon geometries optimized by the same method as the TDDFT calculation [90,91]. Another notable feature of the calculated value of max for this transition is the blue shift on passing from the apolar solvent cyclohexane to the polar solvent acetonitrile. This is typical of the n → ␲* transition of

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Fig. 11. Calculated (HF/6-31+G*) frontier molecular orbitals for S0 (HOMO/LUMO) and T1 (SOMO-1/SOMO) of NQF and the natural transition orbitals (NTO) for the forbidden first excited state (n–␲*) of NQF.

carbonyl compounds and is attributed to non-equilibrium destabilizing dipolar interactions between the excited state solute and the ground state solvation following vertical excitation [92–96]. The principal excitation leading to absorption in the visible part of the spectrum was characterized as being a HOMO–LUMO transition. Fig. 11 shows the calculated Hartree–Fock (HF) orbitals HOMO and LUMO (S0 ) and SOMO and SOMO-1 (T1 ). Notably, the Kohn–Sham orbitals from the DFT calculation were very similarly structured to the HF orbitals. The calculated HF molecular orbitals are consistent with the ␲–␲* nature of the excitation that eventually leads to the triplet intermediate. Table 5 details the frontier orbital energies, the respective energy gaps and the molecular dipole moments. Notably, the energy of the LUMO of the quinones is significantly reduced, more so than the energy of the respective HOMO, in the presence of the polar solvent. This observation can be attributed to greater stabilization of the dipole moment by dispersive and dipolar interactions with the solvent for both the S0 (and presumably the S1 , ␲–␲*) states, as well as the T1 state, which systematically increase on passing from the gas phase to an apolar solvent to a polar solvent. Indeed, the calculated dipole moments for the triplets are larger than for the respective ground states. Therefore the dispersion and or dipolar interactions between the solvent and the excited state will stabilize the excited state in the polar solvent and will result in the observed solvatochromic red-shift for the ␲–␲* transition [97,98]. The calculated gas phase vertical transition (VT) triplet energies (G) for both NQP and NQF are 44 kcal/mol and the optimized (OPT) gas phase T1 energies are 38.9 and 37.1 kcal/mol, respectively (Table 6). In the case of the solvent (acetonitrile) optimized structures the corresponding values (G) for NQP and NQF are 34.6 and 32.9 kcal/mol, respectively. The calculated triplet energies are consistent with the experimental findings that the triplet structures can readily transfer energy to triplet oxygen to form singlet oxygen and are consistent with the observation that the triplets of 1a and 2a are not quenched by 1,3-cyclohexadiene but are quenched by ␤-carotene. Further, the calculated triplet energies are consistent with the known reactivity of triplet 1,2-naphthoquinone [99]. Analysis of the bond lengths and some important angles of the furano- and pyrano-naphthoquinone structures (Table 7, Fig. 12) reveals ground state (S0 ) structures typical of an ortho˚ naphthoquinone with long C4 C9 single bonds (about 1.55 A)

˚ between the 1,2-diketo moiety and a double bond C7 C8 (1.36 A). After excitation and inter-system crossing (ISC) to the T1 state the single bonds of the naphthoquinone structure (C4 C5 , C4 C9 , C8 C9 and C6 C7 ) are all reduced in length and the C O bonds (C4 O1 and C9 O2 ) are elongated consistent with “isomerization” to an aromatic system possessing an ortho-dioxi-diradical moiety (Fig. 12). Notably, the increase in the length of the C9 O2 bond is almost twice that of the C4 O1 bond. The structural change involving the increase in the bond length of C7 C8 results in the largest change, amongst all the relevant bond angles, to the bond angle C6 C7 O3 , where this bond angle opens from 119.7◦ to 125.2◦ (for NQF) and 112.7◦ to about 116.3◦ (an average of the GP and ACN structure values for NQP). An analysis of the ChelpG atomic charges for both NQF and NQP (Table 8) reveals that in the S0 state, of the two carbonyl groups, O2 has approximately 10–12% more electron density both in the gas phase and in solution in comparison to O1 . However, after excitation and ISC there is an inversion of the electron density distribution and O2 is about 10% more electrophilic in comparison to O1 both in the gas phase and in solution. Considerable reorganization of the electron density of the carbon atoms of the quinoid moiety occurs on passing from S0 to T1 . In general carbon atoms with an excess of electron density loose electron density and carbon atoms that were deficient in electron density gain electron density. Overall, the reorganization of electron density is consistent with the formulation of the structure of the T1 state as having an ortho-dioxi-diradical type structure (Fig. 12). Notably, the absolute ChelpG values for the oxygen atoms of the carbonyl groups of solvated NQF-T1 and NQP-T1 are to all extents and purposes equal to one another but in the gas phase O1 and O2 of NQP-T1 are more electrophilic in comparison to NQF-T1 . Given the observation that the respective calculated charges for O1 and O2 of solvated NQP-T1 and NQF-T1 , and the respective C4 O1 and C9 O2 bond lengths, are equivalent it is perhaps reasonable to assume a similar reactivity for the two triplets in acetonitrile in the absence of any other factors. In a similar fashion to previous studies [80,100–102], the hydrogen abstraction reaction was modelled by: (1) investigation of ground state hydrogen bonded quinone-phenol complexes (NQF-HOPh and NQP-HOPh); (2) vertical excitation of the hydrogen bonded complexes to a T1 state; (3) optimization of the T1 complexes; (4) localization of transition states (TS) for hydrogen abstraction and; (5) product formation, a triplet radical pair (TRP).

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Table 5 Calculated energies of the frontier orbitals, the energy gap and dipole moment for gas phase and solvent (acetonitrile or cyclohexane) optimized structures NQP (1) and NQF (2).

Solvent

NQP (1) (hartrees)a Gas phase

NQP (1) (hartrees)a cy-C6 H12

NQP (1) (hartrees)a Acetonitrile

NQF (2) (hartrees)a Gas phase

NQF (2) (hartrees)a cy-C6 H12

NQF (2) (hartrees)a Acetonitrile

LUMO HOMO Energy gap S0 Dipole moment (D) T1 Dipole moment (D)

−0.11864 −0.24520 0.12656 (3.44 eV) 6.81 8.48

−0.12138 −0.24497 0.12359 (3.36 eV) 7.92 10.12

−0.12655 −0.24524 0.11869 (3.23 eV) 9.97 13.07

−0.12141 −0.24350 0.12209 (3.32 eV) 6.47 7.93

−0.12365 −0.24300 0.11935 (3.25 eV) 7.56 9.40

−0.12795 −0.24288 0.11493 (3.13 eV) 9.56 12.13

a

B3LYP/6-311++G**//6-31+G*.

Table 6 The energy difference ( (U)B3LYP/6-311++G**//6-31G*) between S0 and stationary points on the reaction coordinate. Energies (kcal/mol)

NQFS0 -T1VT a

NQFS0 -T1 b

NQPS0 -T1VT a

NQPS0 -T1 b

H298.15 (GP)c G298.15 (GP)c H298.15 (sol)c G298.15 (sol)c

43.9

37.7 37.1 33.5 32.9

44.0

39.7 38.9 35.4 34.6

S0 -T1VT a

S0 -T1 b

S0 -TSe

S0 -TRPf

45.7

36.5 36.8 7.74

34.6 34.6 5.54

27.0 26.6 7.42

34.4 33.3 12.39

35.0 35.0 10.85

25.5 25.0 11.53

42.5

45.0

NQF-Phenol structuresd NQF-HOPh – gas phase structures

H298.15 G298.15 DM (debeyes)g

7.89; 7.20

NQF-HOPh – solvated structures, solvent = acetonitriled H298.15 42.2 G298.15 DM (debeyes)g 11.30; 12.49

a VT, vertical transition; the values of H and G for a calculated structure are equivalent because they use the same respective correction factors from the S0 frequency calculation; b Fully optimized T1 state. c GP, gas phase; sol, solvated structure (solvent = acetonitrile). d The energies refer to structures deriving from reaction at site d (see Fig. 13) of NQF. e TS, transition state. f TRP, triplet radical pair. g DM, dipole moment, in the horizontal order S0 , T1VT , T1 , TS, TRP.

Fig. 12. Relevant atom numbering and schematic representation of the structures of NQP and NQF before and after excitation.

The complexation of phenol to NQF and NQP was investigated by calculating the four possible hydrogen bonded complexes between phenol and the 1,2-diketone moiety. These complexes were used as starting points to evaluate the relative energies of the quinonephenol triplet complexes (NQF-HOPh-T1 ) and triplet radical pairs (NQFH-OPh-TRP). The triplet structures were in turn used to localize transition state structures. This strategy was applied to both reactions of NQF and NQP with phenol. However, only in the case of NQF was it possible to locate a complete sequence of relevant stationery points when using rigorous convergence criteria. 3.5. Hydrogen abstraction from phenol by triplet NQF Of the four possible ground state hydrogen bonded complexes between phenol and NQF (NQF-HOPh-S0 ), the structure forming a hydrogen bond at position d (Fig. 13) was found to be the thermodynamically more stable isomer both in the gas phase and via a continuum solvation model (IEF-PCM). This observation is

consistent with the finding that O2 of both NQP and NQF was found to have the larger negative charge in the S0 state. In the case of NQF, optimization of the four possible T1 complexes (NQFHOPh-T1 ) resulted in the finding that only T1 complexes involving interaction of the phenol with NQF at sites a and d could be localized and the T1 complex at site d was found to be 1 kcal/mol (total electronic energy, TEE) more stable (H = 0.84 kcal/mol more stable whereas G = 1.27 kcal/mol less stable). In a similar fashion attempts to localize triplet radical pairs (TRP) where a hydrogen atom had been transferred to the respective sites a–d resulted only in the localization of products (NQFH-OPh-TRP) resulting from hydrogen transfer to sites a and d. Once again the structure involving site d was energetically favoured, in this case by 5.3 kcal/mol (TEE, H = 5.13 kcal/mol, G = 4.57 kcal/mol). Notably this finding is in line with the structure of the semiquinone radical (1-oxy2-hydroxynaphthalene) deduced from CIDEP spectra after laser irradiation of 1,2-naphthoquinone in the presence of hydrogen donors [51].

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Table 7 Selected geometric parameters of the calculated structures for hydrogen atom abstraction by NQF from PhOH.

. ˚ (GP/Sol)a Bond lengths (A)

NQF-HOPh-S0

NQF-HOPh-T1

NQF-HOPh-TS

NQFH-OPh-TRP

NQF-S0

NQF-T1

NQF-RAb

NQFH-Rc

O3 C7 (GP) (Sol)

1.339 1.331

1.348 1.337

1.355 1.349

1.357 1.350

1.346 1.338

1.349 1.338

1.388 1.373

1.356 1.348

1.366 1.371

1.428 1.427

1.401 1.397

1.392 1.392

1.359 1.364

1.433 1.429

1.368 1.369

1.392 1.393

1.432 1.421

1.432 1.438

1.418 1.420

1.392 1.392

1.442 1.431

1.427 1.435

1.443 1.438

1.388 1.387

C9 O2 (GP) (Sol)

1.235 1.243

1.267 1.269

1.292 1.293

1.344 1.343

1.224 1.232

1.260 1.263

1.254 1.264

1.354 1.354

O2 H13 (GP) (Sol)

1.828 1.769

1.773 1.771

1.290 1.360

0.987 0.994

H13 O14 (GP) (Sol)

0.984 0.989

0.990 0.989

1.126 1.090

1.804 1.744

O14 C15 (GP) (Sol)

1.361 1.361

1.357 1.362

1.313 1.315

1.266 1.268

C4 C9 (GP) (Sol)

1.558 1.556

1.496 1.487

1.482 1.479

1.466 1.465

1.561 1.560

1.501 1.492

1.505 1.496

1.464 1.461

C4 O1 (GP) (Sol)

1.215 1.220

1.238 1.248

1.243 1.253

1.246 1.254

1.216 1.221

1.237 1.248

1.255 1.265

1.244 1.253

O2 O14 (GP) (Sol)

2.805 2.756

2.754 2.758

2.414 2.449

2.748 2.720

C7 C8 (GP) (Sol) C8 C9 (GP) (Sol)

a b c

0.970 0.972

GP, gas phase; sol, solvated (U)B3LYP/6-311++G**//6-31G*. NQF-RA, NQF-radical anion; NQFH-R, NQF semiquinone radical with protonation at site d.

Fig. 13. Four relevant hydrogen bonding sites for phenol to NQF [n = 1] and NQP [n = 2] (a–d) and a schematic representation of the calculated structures involving phenol interacting at site d of NQF.

Attempts to localize transition states (TS) for hydrogen transfer to sites a, b, and c were unsuccessful (using rigorous convergence criteria) but a TS was readily localized for hydrogen transfer to site d (NQF-HOPh-TS). The relative Gibbs free energies for hydrogen abstraction from phenol by NQF to site d of NQF are depicted in Fig. 14 and the relative energies of the calculated stationery points both in the gas phase and in the presence of solvent are detailed in Table 6. Merely as an observation it is interesting to note that in the

transition state (NQF-HOPh-TS) the phenol and NQF are coplanar but in the preceding and following stationery points, phenol and the phenoxyl radical are rotated out of the plane of NQF and NQFH respectively both in the gas phase and in the solvated model. As hydrogen transfer will not necessarily occur directly after excitation of a ground state complex (phenol and triplet NQF will encounter by diffusion) it is reasonable to assume that the triplet state will relax to a minimum and from this relaxed state hydrogen

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Table 8 Selected atomic (ChelpG) charges of the calculated structures for hydrogen atom abstraction by NQF from PhOH.

. Atom/atomic charge (e) (GP/Sol)a

NQF-HOPh-S0

NQF-HOPh-T1

NQF-HOPh-TS

NQFH-OPh-TRP

NQF-S0

NQF-T1

NQF-RAb

NQFH-Rc

O3 (GP) (Sol)

−0.224 −0.227

−0.240 −0.215

−0.276 −0.274

−0.276 −0.290

−0.258 −0.264

−0.261 −0251

−0.313 −0.318

−0.285 −0.292

C7 (GP) (Sol)

0.188 0.269

0.144 0.170

0.140 0.170

0.173 0.189

0.186 0.234

0.131 0.154

0.053 0.108

0.184 0.194

C8 (GP) (Sol)

−0.338 −0.383

−0.136 −0.211

−0.236 −0.270

−0.255 −0.293

−0.007 0.040

−0.248 −0.298

−0.235 −0.231

C9 (GP) (Sol)

0.471 0.538

0.283 0.330

0.231 0.324

0.409 0.458

0.299 0.307

0.397 0.410

0.195 0.217

O2 (GP) (Sol)

−0.535 −0.663

−0.462 −0.559

−0.516 −0.682

−0.528 −0.665

−0.479 −0.593

−0.449 −0.554

−0.635 −0.750

−0.527 −0.585

H13 (GP) (Sol)

0.442 0.508

0.403 0.440

0.471 0.546

0.435 0.546

O14 (GP) (Sol)

−0.637 −0.711

−0.594 −0.661

−0.589 −0.645

−0.559 −0.662

C15 (GP) (Sol)

0.460 0.461

0.438 0.411

0.493 0.591

0.580 0.664

C4 (GP) (Sol)

0.418 0.436

0.333 0.333

0.353 0.358

0.385 0.404

0.417 0.446

0.319 0.350

0.291 0.320

0.405 0.417

O1 (GP) (Sol)

−0.430 −0.499

−0.484 −0.597

−0.496 −0.614

−0.494 −0.597

−0.435 −0.512

−0.473 −0.605

−0.581 −0.696

−0.480 −0.594

0.008 0.014

−0.038 0.030

−0.310 −0.519

−0.041 −0.033

Residual charge on NQFd (GP) (Sol) a b c d

−0.0465 −0.0115

0.1970 0.260

0.421 0.465

GP, gas phase; sol, solvated (U)B3LYP/6-311++G**//6-31G*. NQF-RA, NQF-radical anion. NQFH-R, NQF semiquinone radical with protonation at site d. Sum of the ChelpG charges of all the atoms that compose NQF or NQFH in the case of the product NQFH-OPh-TRP.

transfer may occur in an encounter complex. Notably NQF-HOPhT1 structures optimized to a minimum are more energetic than the calculated TS (NQF-HOPh-TS). Therefore hydrogen transfer from phenol to NQF is best described as a barrierless process in the gas phase. Similar barrierless transition states have been observed for other ␣-diketones in hydrogen abstraction reactions from phenol or from 2-propanol (C H abstraction) for which there is experimental evidence in the case of hydrogen abstraction by triplet 9,10-phenanthrenequinone [80,100,103]. Additionally, the energies of the relevant stationery points on the reaction coordinate were calculated by modelling the solvent as a polarizable continuum. The respective energies of the stationery points were marginally smaller in comparison to the gas phase calculations (Table 6). However, the notable difference was that the optimized NQF-HOPh-T1 complex was now less energetic than the NQF-HOPh-TS structure resulting in a very small activation barrier (<1 kcal/mol).

Table 7 details selected geometric parameters of the respective stationery points along the reaction coordinate. Analysis of the bond lengths, principally the bonds involving atoms at the reaction centre C9 O2 , O2 H13 , H13 O14 , and O14 C15 and the interatomic distance of O2 O14 reveals features of the mechanism for hydrogen abstraction. The quinone C9 O2 , and to a much lesser extent C4 O1 , bond lengths increase along the reaction coordinate from NQF-HOPh-S0 , NQF-HOPh-T1 , NQF-HOPh-TS to NQFH-OPh-TRP. A comparison can be made with the structures NQF-S0 , NQF-T1 , NQF-RA (NQF-radical anion) and NQFH-R (the NQF semiquinone radical). Although the absolute values of the bond lengths for both sequences are slightly different, they generally follow the same trends and differences can be attributed to the presence of the phenol or the phenoxyl radical in the former sequence. As commented earlier for the structures of NQF-T1 and NQP-T1 the C9 O2 bond is longer than the C4 O1 bond in the T1 complex NQF-HOPhT1 . The increased bond length and the lesser excess of electron

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27

Fig. 14. Optimized geometries of the gas phase calculated structures are represented within a schematic reaction coordinate (relative values of Gibb’s free energies are not to scale).

density results in O2 being more electrophilic than O1 and therefore presumably more reactive than O1 for hydrogen atom abstraction. Specifically, with respect to bonds along the reaction coordinate (C9 O2 , O2 H13 , H13 O14 and O14 C15 ) and the inter-atomic distance O2 O14 , the substrates NQF and phenol are at their largest distance apart in the NQF-HOPh-S0 ground state complex. In the NQF-HOPh-T1 complex the O2 H13 bond length has been reduced to a greater extent than the increase in the bond length C9 O2 whilst the bond lengths H13 O14 and O14 C15 are more or less unchanged resulting in an overall shorter O2 O14 inter-atomic distance. On passing from the NQF-HOPh-T1 complex to NQF-HOPh-TS the C9 O2 bond length increases by 2% and the O2 H13 distance is reduced by 27%. These changes are accompanied by a 14% increase in the H13 O14 and a 3% decrease in the O14 C15 bond lengths. Notably in the TS the O2 H13 distance is 13% greater than the H13 O14 bond length in the gas phase and 25% greater in the solvated structures revealing that H13 has not yet been transferred. The inter-atomic distance O2 O14 is smallest at the TS. On passing from NQF-HOPh-TS to NQFH-OPh-TRP the C9 O2 bond length increases by 4% and the proton/hydrogen atom (H13 ) is completely transferred, the O2 H13 distance decreases by 23% (GP) or by 27% (sol). Correspondingly, the H13 O14 distance increases by 60% (both GP and sol) and the O14 C15 distance decreases by 4% resulting in the formation of the phenoxyl radical. The final O2 O14 interatomic distance (NQFH-OPh-TRP) is very similar to that observed for the triplet complex NQF-HOPh-T1 and consistent with the formation of two new products that are closely associated. The analysis of the bond lengths along the reaction coordinate reveals an early transition state for the “hydrogen atom” transfer and when solvation is taken into account the transition state was found to occur still earlier on the reaction coordinate. The charge flux along the reaction coordinate was investigated by analyzing the ChelpG atomic charges of the stationery points. Table 8 presents some selected ChelpG data for atoms of key structural elements of the stationery points along the reaction coordinate as well as the respective atoms of NQF-S0 , NQF-T1 , NQF-RA and NQFH-R for comparative purposes. As part of the analysis the

residual charge on NQF was calculated from the sum of the atomic charges of all the atoms (note not all atoms are listed in Table 8) that compose NQF or NQFH in the case of the product NQFH-OPh-TRP. The residual charge values reveal an excess of electron density on NQF in the TS (0.31e in the GP and 0.52e in solution) but no charge transfer in the NQF-HOPh-T1 complex. Taken in hand with the observation that the hydrogen atom of the phenol is more closely associated with the phenol than with the triplet ketone in the TS (and more so in solution than in the gas phase) then the analysis reveals that electron transfer occurs in the transition state and not in the triplet complex as seen with highly reactive n, ␲* and ␲,␲* ketones with particularly low reduction potentials [80,81]. 4. Conclusion In conclusion, it was shown that 1,2-naphthoquinones 1a–f and 2a–f are able to act as photosensitizers for the one-electron oxidation of N-acetyl-l-tryptophan methyl ester (NATME) and 4-methoxyphenol. Additionally, efficient singlet oxygen formation was measured for these lapachone analogues (˚ = 0.7). The results clearly demonstrate that 1a–f and 2a–f are able to undergo photosensitized type I and type II mechanisms with biological substrates, and that their reactivity is similar to other lapachones previously reported in the literature. TD-DFT calculations were used to calculate UV–vis spectra of model compounds with the furano- and pyrano-1,2naphthoquinone structures (NQF and NQP). The principal transition in the visible part of the spectrum was characterized as being a HOMO–LUMO transition involving ␲–␲* orbitals. The use of the hybrid functional CAM-B3LYP and IEF-PCM resulted in a faithful reproduction of the solvatochromic shift observed for each family as well as the reproduction of the difference in max for each family of compounds for the ␲–␲* transition in the visible part of the spectrum. The rigid, tensioned, NQF resulted in a smaller HOMO–LUMO energy gap and consequently the longer value of max in comparison with NQP. Additionally, the forbidden n–␲* transition was characterized and its assignment as a shoulder on

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the low energy side of the ␲–␲* transition (above 500 nm as seen in the experimental spectra) was based upon TDDFT calculations. DFT calculations were used to calculate the structure, the energy, and the reactivity of the first triplet state. The effect of solvent was modelled by use of IEF-PCM calculations where the solvent resulted in stabilization of the calculated structures relative to the gas phase. Optimized triplet energies were found to be in good agreement with the experimental results for energy transfer from T1 NQP and NQF derivatives. The reactivity of NQF in the hydrogen abstraction reaction from phenol was successfully modelled both in the gas phase and in the presence of solvent modelled as a dielectric polarizable continuum. Hydrogen transfer was found to preferentially occur to the outside of the 1,2-diketone system and to the carbonyl group that was most basic in the S0 state but also the most electrophilic in the T1 state. In the gas phase, hydrogen abstraction was characterized as a barrierless process but in solution a small (H < 1 kcal/mol) barrier was calculated. The results are consistent in that analysis of the geometries and of the charge flux through the stationery points along the reaction coordinate revealed that electron transfer precedes proton transfer in an early transition state. Therefore in the gas phase there will be no barrier to proton transfer in the transition state whilst in solution there will be a cost involved with solvent reorganization because of changes in the dipole moment of the structures along the steps of the reaction coordinate. Acknowledgments This study was supported by the Brazilian agencies: CAPES (Coordenac¸ão de Aperfeic¸oamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), and FAPERJ (Fundac¸ão de Amparo a pesquisa do Estado do Rio de Janeiro). References [1] E.N. da Silva, M. de Souza, A.V. Pinto, M. Pinto, M.O.F. Goulart, F.W.A. Barros, C. Pessoa, L.V. Costa-Lotufo, R.C. Montenegro, M.O. de Moraes, V.F. Ferreira, Synthesis and potent antitumor activity of new arylamino derivatives of nor-beta-lapachone and nor-alpha-lapachone, Bioorg. Med. Chem. 15 (2007) 7035–7041. [2] F.D. da Silva, S.B. Ferreira, C.R. Kaiser, A.C. Pinto, V.F. Ferreira, Synthesis of alpha- and beta-lapachone derivatives from hetero Diels–Alder trapping of alkyl and aryl o-quinone methides, J. Braz. Chem. Soc. 20 (2009) 1478–1482. [3] M.N. Silva, V.F. Ferreira, M.C.B.V. de Souza, Um Panorama Atual da Quimica e da Farmacologia de Naftoquinonas, com Ênfase na beta-Lapachona e Derivados, Quím. Nova 26 (2003) 407–416. [4] C. Asche, Antitumour quinones, Mini-Rev. Med. Chem. 5 (2005) 449–467. [5] A.F. dos Santos, P.A.L. Ferraz, F.C. de Abreu, E. Chiari, M.O.F. Goulart, A.E.G. Sant’Ana, Molluscicidal and trypanocidal activities of lapachol derivatives, Planta Med. 67 (2001) 92–93. [6] A.F. dos Santos, P.A.L. Ferraz, A.V. Pinto, M.C.F.R. Pinto, M.O.F. Goulart, A.E.G. Sant’Ana, Molluscicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones and derivatives, Int. J. Parasitol. 30 (2000) 1199–1202. [7] M.J. Teixeira, Y.M. de Almeida, J.R. Viana, J.G. Holanda, T.P. Rodrigues, J.R.C. Prata, I.V.B. Coelho, V.S. Rao, M.M.L. Pompeu, In vitro and in vivo leishmanicidal activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol), Phytother. Res. 15 (2001) 44–48. [8] E.R. Almeida, A.A. da Silva, E.R. dos Santos, C.A.C. Lopes, Antiinflammatory action of lapachol, J. Ethnopharmacol. 29 (1990) 239–241. [9] K.O. Eyong, P.S. Kumar, V. Kuete, G.N. Folefoc, E.A. Nkengfack, S. Baskaran, Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol, Bioorg. Med. Chem. Lett. 18 (2008) 5387–5390. [10] B.H. Kim, J. Yoo, S.H. Park, J.K. Jung, H. Cho, Y.S. Chung, Synthesis and evaluation of antitumor activity of novel 1,4-naphthoquinone derivatives (IV), Arch. Pharm. Res. 29 (2006) 123–130. [11] C.S. Medeiros, N.T. Pontes, C.A. Camara, J.V. Lima, P.C. Oliveira, S.A. Lemos, A.F.G. Leal, J.O.C. Brandao, R.P. Neves, Antifungal activity of the naphthoquinone beta-lapachone against disseminated infection with Cryptococcus neoformans var. neoformans in dexamethasone-immunosuppressed Swiss mice, Braz. J. Med. Biol. Res. 43 (2010) 345–349. [12] A. Riffel, L.F. Medina, V. Stefani, R.C. Santos, D. Bizani, A. Brandelli, In vitro antimicrobial activity of a new series of 1,4-naphthoquinones, Braz. J. Med. Biol. Res. 35 (2002) 811–818.

[13] M.M.M. Santos, N. Faria, J. Iley, S.J. Coles, M.B. Hursthouse, M.L. Martins, R. Moreira, Reaction of naphthoquinones with substituted nitromethanes. Facile synthesis and antifungal activity of naphtho[2,3-d]isoxazole-4,9-diones, Bioorg. Med. Chem. Lett. 20 (2010) 193–195. [14] V.K. Tandon, H.K. Maurya, N.N. Mishra, P.K. Shukia, Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4naphthoquinones as potent antifungal and antibacterial agents, Eur. J. Med. Chem. 44 (2009) 3130–3137. [15] K.C.G. De Moura, F.S. Emery, C. Neves-Pinto, M.C.F.R. Pinto, A.P. Dantas, K. Salomão, S.L. De Castro, A.V. Pinto, Trypanocidal activity of isolated naphthoquinones from Tabebuia and some heterocyclic derivatives: a review from an interdisciplinary study, J. Braz. Chem. Soc. 12 (2001) 325–338. [16] C.N. Pinto, A.P. Dantas, K.C.G. De Moura, F.S. Emery, P.F. Polequevitch, M.C.F.R. Pinto, S.L. De Castro, A.V. Pinto, Chemical reactivity studies with naphthoquinones from Tabebuia with antitrypanosomal efficacy, Arzneimittel-Forsch 50 (2000) 1120–1128. [17] E.N. Silva, R.F.S. Menna-Barreto, M. Pinto, R.S.F. Silva, D.V. Teixeira, M. de Souza, C.A. De Simone, S.L. De Castro, V.F. Ferreira, A.V. Pinto, Naphthoquinoidal [1,2,3]-triazole, a new structural moiety active against Trypanosoma cruzi, Eur. J. Med. Chem. 43 (2008) 1774–1780. [18] C.L. Zani, E. Chiarib, A.U. Krettlia, S.M. Murta, M.L. Cunninghamc, A.H. Fairlambc, A. Romanha, Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiophen-4,9-quinones, Bioorg. Med. Chem. 5 (1997) 2185–2192. [19] R. Docampo, F.S. Cruz, A. Boveris, R.P. Muniz, D.M. Esquivel, Biochem. Pharmacol. 28 (1979) 723–728. [20] G. Powis, Metabolism and reactions of quinoid anticancer agents, Pharmacol. Ther. 35 (1987) 57–162. [21] D.M. Santos, M.M.M. Santos, R. Moreira, S. Sola, C.M.P. Rodrigues, Synthetic condensed 1,4-naphthoquinone derivative shifts neural stem cell differentiation by regulating redox state, Mol. Neurobiol. 47 (2013) 313–324. [22] F.S. Cruz, R. Docampo, W.D. Souza, Effect of beta-lapachone on hydrogenperoxide production in Trypanosoma cruzi, Acta Trop. 35 (1978) 35–40. [23] R. Docampo, J.N. Lopes, F.S. Cruz, W.D. Souza, Trypanosoma cruzi: ultrastructural and metabolic alterations of epimastigotes by beta-lapachone, Exp. Parasitol. 42 (1977) 142–149. [24] C.O. Salas, M. Faundez, A. Morello, J.D. Maya, R.A. Tapia, Natural and synthetic naphthoquinones active against Trypanosoma cruzi: an initial step towards new drugs for Chagas disease, Curr. Med. Chem. 18 (2011) 144–161. [25] J.J. Pink, S.M. Planchon, C. Tagliarino, M.E. Varnes, D. Siegel, D.A. Boothman, NAD(P)H: quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity, J. Biol. Chem. 275 (2000) 5416–5424. [26] S.M. Planchon, J.J. Pink, C. Tagliarino, W.G. Bornmann, M.E. Varnes, D.A. Boothman, Beta-lapachone-induced apoptosis in human prostate cancer cells: involvement of NQO1/xip3, Exp. Cell Res. 267 (2001) 95–106. [27] S.M. Planchon, S. Wuerzberger, B. Frydman, D.T. Witiak, P. Hutson, D.R. Church, G. Wilding, D.A. Boothman, Beta-lapachone mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cell – AP53-independent response, Cancer Res. 55 (1995) 3706–3711. [28] K. Schaffnersabba, K.H. Schmidtruppin, W. Wehrli, A.R. Schuerch, J.W.F. Wasley, Beta-lapachone synthesis of derivatives and activities in tumormodels, J. Med. Chem. 27 (1984) 990–994. [29] S.M. Wuerzberger, J.J. Pink, S.M. Planchon, K.L. Byers, W.G. Bornmann, D.A. Boothman, Induction of apoptosis in MCF-7: WS8 breast cancer cells by betalapachone, Cancer Res. 58 (1998) 1876–1885. [30] J.L. Bolton, M.A. Trush, T.M. Penning, G. Dryhurst, T.J. Monks, Role of quinones in toxicology, Chem. Res. Toxicol. 13 (2000) 135–160. [31] M.E. Dolan, B. Frydman, C.B. Thompson, A.M. Diamond, B.J. Garbiras, A.R. Safa, W.T. Beck, L. Marton, Effects of 1,2-naphthoquinones on human tumor cell growth and lack of cross-resistance with other anticancer agents, Anti-Cancer Drugs 9 (1998) 437–448. [32] J.S. Driscoll, G.F. Hazard, H.B. Wood, Structure-antitumor activity relationships among quinone derivatives, Cancer Chemother Rep 4 (2 (Suppl.)) (1974) 1–27. [33] C.J. Li, I. Averboukh, A.B. Pardee, Beta-lapachone, a novel DNA topoisomeraseI inhibitor with a mode of action different from camptothecin, J. Biol. Chem. 268 (1993) 22463–22468. [34] J.N. Lopes, F.S. Cruz, R. Docampo, In vitro and in vivo evaluation of toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi, Ann. Trop. Med. Parasitol. 72 (1978) 523–531. [35] D.A. Boothman, D.K. Trask, A.B. Pardee, Inhibition of potentially lethal DNA damage repair in human-tumor cells by beta-lapachone, an activator of topoisomerase-1, Cancer Res. 49 (1989) 605–612. [36] B. Frydman, L. Marton, J.S. Sun, K. Neder, D.T. Witiak, A.A. Liu, H.M. Wang, Y. Mao, H.V. Wu, M.M. Sanders, L.F. Liu, Induction of DNA topoisomerase II-mediated DNA cleavage by beta-lapachone and related naphthoquinones, Cancer Res. 57 (1997) 620–627. [37] M.S. Bentle, E.A. Bey, Y. Dong, K.E. Reinicke, D.A. Boothman, New tricks for old drugs: the anticarcinogenic potential of DNA repair inhibitors, J. Mol. Histol. 37 (2006) 203–218. [38] J.L. Martindale, N.J. Holbrook, Cellular response to oxidative stress: signaling for suicide and survival, J. Cell. Physiol. 192 (2002) 1–15. [39] A. Michaeli, J. Feitelson, Reactivity of singlet oxygen toward amino-acids and peptides, Photochem. Photobiol. 59 (1994) 284–289. [40] A. Michaeli, J. Feitelson, Reactivity of singlet oxygen toward large peptides, Photochem. Photobiol. 61 (1995) 255–260.

N.C. de Lucas et al. / Journal of Photochemistry and Photobiology A: Chemistry 276 (2013) 16–30 [41] G. Stark, Functional consequences of oxidative membrane damage, J. Membr. Biol. 205 (2005) 1–16. [42] J.L. Ravanat, P. Di Mascio, G.R. Martinez, M.H.G. Medeiros, J. Cadet, Singlet oxygen induces oxidation of cellular DNA, J. Biol. Chem. 275 (2000) 40601–40604. [43] S. Encinas, N. Belmadoui, M.J. Climent, S. Gil, M.A. Miranda, Photosensitization of thymine nucleobase by benzophenone derivatives as models for photoinduced DNA damage: Paterno–Buchi vs energy and electron transfer processes, Chem. Res. Toxicol. 17 (2004) 857–862. [44] V. Lhiaubet, N. Paillous, N. Chouini-Lalanne, Comparison of DNA damage photoinduced by ketoprofen, fenofibric acid and benzophenone via electron and energy transfer, Photochem. Photobiol. 74 (2001) 670–678. [45] V. Lhiaubet-Vallet, M.A. Miranda, Phototoxicity of drugs, in: A. Griesbeck, M. Oelgemöller, F. Ghetti (Eds.), CRC Handbook of Organic Photochemistry and Photobiology, third ed., CRC Press/Taylor and Francis, Boca Raton, FL, 2012, pp. 1541–1551. [46] M.J. Davies, R.J.W. Truscott, Photo-oxidation of proteins and its role in cataractogenesis, J. Photochem. Photobiol. B: Biol. 63 (2001) 114–125. [47] E. Silva, R. Ugarte, A. Andrade, A.M. Edwards, Riboflavin-sensitized photoprocesses of tryptophan, J. Photochem. Photobiol. B: Biol. 23 (1994) 43–48. [48] S.M. Hubig, T.M. Bockman, J.K. Kochi, Identification of photoexcited singlet quinones and their ultrafast electron-transfer vs intersystem-crossing rates, J. Am. Chem. Soc. 119 (1997) 2926–2935. [49] J.C. Netto-Ferreira, B. Bernardes, A.B.B. Ferreira, M.A. Miranda, Laser flash photolysis study of the triplet reactivity of beta-lapachones, Photochem. Photobiol. Sci. 7 (2008) 467–473. [50] M. Barra, E.D. Harder, J.P. Balfe, Influence of solvent polarity on the photoreactivity of 2–4-ring aromatic ortho-quinones, J. Chem. Soc. Perkin Trans. 2 (1999) 1439–1441. [51] H. Shimoishi, S. Tero-Kubota, K. Akiyama, Y. Ikegami, Influence of solvent polarity on the excited triplet states of non-phosphorescent 1,2-naphthoquinone and phosphorescent 9,10-phenanthrenequinone—time resolved ESR and CIDEP studies, J. Phys. Chem. 93 (1989) 5410–5414. [52] R.S. Becker, L.V. Natarajan, Comprehensive absorption, photophysical chemical, and theoretical study of 2–5-ring aromatic hydrocarbon diones, J. Phys. Chem. 97 (1993) 344–349. [53] J.C. Netto-Ferreira, V. Lhiaubet-Vallet, B.O. Bernardes, A.B.B. Ferreira, M.A. Miranda, Characterization, reactivity and photosensitizing properties of the triplet excited state of alpha-lapachone, Phys. Chem. Chem. Phys. 10 (2008) 6645–6652. [54] J.C. Netto-Ferreira, V. Lhiaubet-Vallet, B.O. Bernardes, A.B.B. Ferreira, M.A. Miranda, Photosensitizing properties of triplet beta-lapachones in acetonitrile solution, Photochem. Photobiol. 85 (2009) 153–159. [55] N.C. de Lucas, R.J. Corrêa, S.J. Garden, G. Santos, R. Rodrigues, C.E.M. Carvalho, S. Ferreira, J.C. Netto-Ferreira, V.F. Ferreira, P. Miro, M.L. Marin, M.A. Miranda, Singlet oxygen production by pyrano and furano 1,4-naphthoquinones in non-aqueous medium, Photochem. Photobiol. Sci. 11 (2012) 1201–1209. [56] S.B. Ferreira, F.D. da Silva, F. Bezerra, M.C.S. Lourenco, C.R. Kaiser, A.C. Pinto, V.F. Ferreira, Synthesis of alpha- and beta-pyran naphthoquinones as a new class of antitubercular agents, Arch Pharm 343 (2010) 81–90. [57] C.P.V. Freire, S.B. Ferreira, N.S.M. Oliveira, A.B.J. Matsuura, I.L. Gama, F.C. da Silva, M.C.B.V. de Souza, E.S. Lima, V.F. Ferreira, Synthesis and biological evaluation of substituted a- and b-2,3-dihydrofuran naphthoquinones as potent anticandidal agents, Med. Chem. Commun. 1 (2010) 229–232. [58] X.H. Ci, R.S. Dasilva, J.L. Goodman, D.E. Nicodem, D.G. Whitten, A reversible photoredox reaction – electron-transfer photoreduction of beta-lapachone by triethylamine, J. Am. Chem. Soc. 110 (1988) 8548–8550. [59] X.H. Ci, R.S. Dasilva, D. Nicodem, D.G. Whitten, Electron and hydrogen-atom transfer mechanisms for the photoreduction of ortho-quinones-visible-light induced photoreactions of beta-lapachone with amines, alcohols and aminoalcohols, J. Am. Chem. Soc. 111 (1989) 1337–1343. [60] J.C. Netto-Ferreira, V. Lhiaubet-Vallet, A.R. da Silva, A.M. da Silva, A.B.B. Ferreira, M.A. Miranda, The photochemical reactivity of triplet betalapachone-3-sulfonic acid towards biological substrates, J. Brazil. Chem. Soc. 21 (2010) 966–972. [61] H.T. Huang, C. Niemann, The kinetics of the a-chymotrypsin catalyzed hydrolysis of acetyl- and nicotinyl-l-tryptophanamide in aqueous solutions at 25◦ and pH 7.9, J. Am. Chem. Soc 73 (1951) 1541–1548. [62] S. Nonell, M. Gonzalez, F.R. Trull, 1H-phenalen-1-one-2-sulfonic acid – an extremely efficient singlet molecular-oxygen sensitizer for aqueous-media, Afinidad 50 (1993) 445–450. [63] A.D. Becke, Density-functional thermochemistry. 3. The role of exact exchange, J. Chem. Phys. 98 (1993) 5648–5652. [64] T.H. Dunning, Gaussian-basis sets for use in correlated molecular calculations. 1. The atoms boron through neon and hydrogen, J. Chem. Phys. 90 (1989) 1007–1023. [65] C.T. Lee, W.T. Yang, R.G. Parr, Development of the Colle-salvetti correlationenergy formula into a functional of the electron-density, Phys. Rev. B 37 (1988) 785–789. [66] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross,

[67] [68] [69] [70]

[71]

[72] [73]

[74] [75] [76]

[77] [78] [79]

[80]

[81] [82] [83] [84]

[85]

[86]

[87]

[88]

[89] [90]

[91]

[92] [93] [94]

[95] [96]

[97] [98]

29

V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, Ö. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian 09, Revision C.01, Gaussian, Inc., Wallingford, CT, 2009. Spartan’10, Wavefunction Inc., Irvine, CA. R. Fletcher, Practical Methods of Optimization, Wiley, New York, 1980. W.H. Koch, M.C. Weinheim, A Chemist’s Guide to Density Functional Theory, 2001. E. Cances, B. Mennucci, J. Tomasi, A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics, J. Chem. Phys. 107 (1997) 3032–3041. B. Mennucci, E. Cances, J. Tomasi, Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method: theoretical bases, computational implementation, and numerical applications, J. Phys. Chem. B 101 (1997) 10506–10517. G. Scalmani, M.J. Frisch, Continuous surface charge polarizable continuum models of solvation. I. General formalism, J. Chem. Phys. 132 (2010). T. Yanai, D.P. Tew, N.C. Handy, A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP), Chem. Phys. Lett. 393 (2004) 51–57. C. Adamo, V. Barone, Toward reliable density functional methods without adjustable parameters: the PBE0 model, J. Chem. Phys. 110 (1999) 6158–6170. M. Ernzerhof, G.E. Scuseria, Assessment of the Perdew–Burke–Ernzerhof exchange-correlation functional, J. Chem. Phys. 110 (1999) 5029–5036. C.M. Breneman, K.B. Wiberg, Determining atom-centered monopoles from molecular electrostatic potentials – the need for high sampling density in formanide conformational-analysis, J. Comput. Chem. 11 (1990) 361–373. S.L. Murov, I. Carmichael, G.L. Hug, Handbook of Photochemistry, Marcel Dekler, Inc., New York, 1993. J.C. Scaiano, Laser flash photolysis studies of the reactions of some 1,4biradicals, Acc. Chem. Res. 15 (1982) 252–258. N.C. de Lucas, J.C. Netto-Ferreira, Laser flash photolysis study of the hydrogen abstraction properties of acenaphthequinone and 1-acenaphthenone, J. Photochem. Photobiol. A: Chem. 116 (1998) 203–208. N.C. de Lucas, R.J. Correa, A.C.C. Albuquerque, C.L. Firme, S.J. Garden, A.R. Bertoti, J.C. Netto-Ferreira, Laser flash photolysis of 1,2-diketopyracene and a theoretical study of the phenolic hydrogen abstraction by the triplet state of cyclic alpha-diketones, J. Phys. Chem. A 111 (2007) 1117–1122. E.C. Lathioor, W.J. Leigh, Bimolecular hydrogen abstraction from phenols by aromatic ketone triplets, Photochem. Photobiol. 82 (2006) 291–300. Y.P. Tsentalovich, O.A. Snytnikova, R.Z. Sagdeev, Properties of excited states of aqueous tryptophan, J. Photochem. Photobiol. A: Chem. 162 (2004) 371–379. G. Merenyi, J. Lind, X.H. Shen, Electron-transfer from indoles, phenol, and sulfite (SO3 (2−)) to chlorine dioxide (ClO2 ), J. Phys. Chem 92 (1988) 134–137. S. Steenken, P. Neta, One-electron redox potentials of phenols. Hydroxy- and aminophenols and related compounds of biologlcal interest, J. Phys. Chem. 86 (1982) 3661–3667. E.A.G. Bremond, J. Kieffer, C. Adamo, A reliable method for fitting TD-DFT transitions to experimental UV–visible spectra, Theochem. J. Mol. Struct. 954 (2010) 52–56. D. Jacquemin, V. Wathelet, E.A. Perpete, C. Adamo, Extensive TD-DFT benchmark: singlet-excited states of organic molecules, J. Chem. Theory Comput. 5 (2009) 2420–2435. D. Jacquemin, E.A. Perpete, G.E. Scuseria, I. Ciofini, C. Adamo, TD-DFT performance for the visible absorption spectra of organic dyes: conventional versus long-range hybrids, J. Chem. Theory Comput. 4 (2008) 123–135. D. Jacquemin, E.A. Perpete, I. Ciofini, C. Adamo, Assessment of functionals for TD-DFT calculations of singlet–triplet transitions, J. Chem. Theory Comput. 6 (2010) 1532–1537. R.L. Martin, Natural transition orbitals, J. Chem. Phys. 118 (2003) 4775–4777. D. Jacquemin, E.A. Perpete, G.E. Scuseria, I. Ciofini, C. Adamo, Extensive TDDFT investigation of the first electronic transition in substituted azobenzenes, Chem. Phys. Lett. 465 (2008) 226–229. D. Jacquemin, E.A. Perpete, O.A. Vydrov, G.E. Scuseria, C. Adamo, Assessment of long-range corrected functionals performance for n → ␲(*) transitions in organic dyes, J. Chem. Phys. 127 (2007). M. Cossi, V. Barone, Solvent effect on vertical electronic transitions by the polarizable continuum model, J. Chem. Phys. 112 (2000) 2427–2435. M. Cossi, V. Barone, Time-dependent density functional theory for molecules in liquid solutions, J. Chem. Phys. 115 (2001) 4708–4717. A. DeFusco, N. Minezawa, L.V. Slipchenko, F. Zahariev, M.S. Gordon, Modeling solvent effects on electronic excited states, J. Phys. Chem. Lett. 2 (2011) 2184–2192. H. McConnell, Effect of polar solvents on the absorption frequency of N–␲electronic transitions, J. Chem. Phys. 20 (1952) 700–704. B. Mennucci, R. Cammi, J. Tomasi, Excited states and solvatochromic shifts within a nonequilibrium solvation approach: a new formulation of the integral equation formalism method at the self-consistent field, configuration interaction, and multiconfiguration self-consistent field level, J. Chem. Phys 109 (1998) 2798–2807. H.C. Longuethiggins, J.A. Pople, Electronic spectral shifts of nonpolar molecules in nonpolar solvents, J. Chem. Phys. 27 (1957) 192–194. T. Renger, B. Grundkotter, M.E.A. Madjet, F. Muh, Theory of solvatochromic shifts in nonpolar solvents reveals a new spectroscopic rule, Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 13235–13240.

30

N.C. de Lucas et al. / Journal of Photochemistry and Photobiology A: Chemistry 276 (2013) 16–30

[99] Y. Pan, Y. Fu, S. Liu, H. Yu, Y. Gao, Q. Guo, S. Yu, Studies on photoinduced H-atom and electron transfer reaction of o-naphthoquinones by laser flash photolysis, J. Phys. Chem. A. 110 (2006) 7316–7322. [100] N.C. de Lucas, M.M. Elias, C.L. Firme, R.J. Corrêa, S.J. Garden, J.C. Netto-Ferreira, D.E. Nicodem, A combined laser flash photolysis, density functional theory and atoms in molecules study of the photochemical hydrogen abstraction by pyrene-4,5-dione, J. Photochem. Photobiol. A. Chem. 201 (2009) 1–7. [101] N.C. de Lucas, H.S. Fraga, C.P. Cardoso, R.J. Correa, S.J. Garden, J.C. NettoFerreira, A laser flash photolysis and theoretical study of hydrogen abstraction

from phenols by triplet ␣-naphthoflavone, Phys. Chem. Chem. Phys. 12 (2010) 10746–10753. [102] C.L. Firme, S.J. Garden, N.C. de Lucas, D.E. Nicodem, R.J. Correa, Theoretical study of photochemical hydrogen abstraction by triplet aliphatic carbonyls by using density functional theory, J. Phys. Chem. A 117 (2013) 439–450. [103] D.E. Nicodem, R.S. Silva, D.M. Togashi, M.F.V. Cunha, Solvent effects on the quenching of the equilibrating n,␲* and ␲,␲* triplet sate of 9,10phenanthrenequinone by 2-propanol, J. Photochem. Photobiol. A: Chem. 175 (2005) 154–158.