Triplet Excited States of Cyclic Disulfides and Related Compounds

Jan 27, 2011 - Saroja Ginagunta and Götz Bucher*. WestCHEM, Department of Chemistry, University of Glasgow, Joseph-Black-Building, University Avenue,...
0 downloads 0 Views 4MB Size
Download PDF
540

J. Phys. Chem. A 2011, 115, 540–546

Triplet Excited States of Cyclic Disulfides and Related Compounds: Electronic Structures, Geometries, Energies, and Decay Saroja Ginagunta and Go¨tz Bucher* WestCHEM, Department of Chemistry, UniVersity of Glasgow, Joseph-Black-Building, UniVersity AVenue, Glasgow G12 8QQ, United Kingdom ReceiVed: August 24, 2010; ReVised Manuscript ReceiVed: NoVember 24, 2010

We have performed a computational study on the properties of a series of heterocycles bearing two adjacent heteroatoms, focusing on the structures and electronic properties of their first excited triplet states. If the heteroatoms are both heavy chalcogens (S, Se, or Te) or isoelectronic species, then the lowest excited triplet state usually has (π*, σ*) character. The triplet energies are fairly low (30-50 kcal mol-1). The (π*, σ*) triplet states are characterized by a significantly lengthened bond between the two heteroatoms. Thus, in 1,2-dithiolane (1b), the S-S bond length is calculated to be 2.088 Å in the singlet ground state and 2.568 Å in the first triplet excited state. The spin density is predicted to be localized almost exclusively on the sulfur atoms. Replacing one heavy chalcogen atom by an oxygen atom or an NR group results in a significant destabilization of the (π*, σ*) triplet excited state, which then no longer is lower in energy than an openchain biradical. The size of the heterocyclic ring also contributes to the stability of the (π*, σ*) triplet state, with five-membered rings being more favorable than six-membered rings. Benzoannulation, finally, usually lowers the energy of the (π*, σ*) triplet excited states. If one of the heteroatoms is an oxygen or nitrogen atom, however, the corresponding lowest triplet states are better described as σ,π-biradicals. Introduction Lipoic acid 1a is a cyclic disulfide that plays a crucial role as a coenzyme in the Krebs cycle in biochemistry. Its physiological ubiquity poses questions about further roles that it may have in the body, such as serving as an antioxidant.1-5 To test the redox properties of 1a, we have investigated the photochemistry of 1a in an aqueous medium and in acetonitrile solution.6-8 Both the radical cation and the radical anion of 1a were formed upon 266 nm laser flash photolysis (LFP) of 1a in an aqueous solution.8 In contrast, 355 nm LFP of 1a in an acetonitrile solution gave rise to a fairly short-lived (τ ) 75 ns, λmax ) 322, 280 nm) intermediate that we assigned to the first excited triplet state of 1a.8 We based this assignment on a comparison of the experimental transient spectrum with a calculated UV/vis spectrum of 31a and on the typical reactivity toward oxygen and β-carotene. A number of questions about the electronic structure and the reactivity of 31a, however, remain unanswered. In this contribution, we will explore in detail the electronic structure of 31a, we will propose a possible mechanism for its decay, and we will embark on a study of triplet states of similar molecules containing two adjacent heteroatoms. In terms of methodology, we employ B3LYP and M05-2X as DFT methods and CCSD(T) as a benchmark method for a number of selected small systems. Computational Studies on the Electronic Structure of Triplet States of Cyclic Disulfides and Related Compounds. Lipoic acid 1a itself is not an ideal object for an extended computational study because it contains a sizable side chain, which introduces many degrees of conformational freedom. Since our initial publication, further experimental work has shown that the -(CH2)4-COOH side chain present in 1a can be changed to a -(CH2)4-CONH2 side chain without altering the triplet lifetime or the transient spectrum.9 This leads us to * Corresponding author. E-mail: [email protected].

reason that the nature of the side chain probably does not play a significant role here. As a model substance for 1a, we have therefore investigated 1,2-dithiolane 1b, which is devoid of the pentanoic acid side chain present in lipoic acid and lipoic acid amide. We used the B3LYP hybrid functional and the M05-2X method in combination with a cc-pVTZ basis set. To check the reliability of the DFT results, some stationary points relevant to the photochemistry of 1b were additionally calculated at the ROHF-CCSD(T)/cc-pVTZ level of theory. Figure 1 shows the results obtained for 1b.

According to Figure 1, the excitation of 1b to the triplet spin manifold results in a significant lengthening of the sulfur-sulfur bond, from RS-S ) 2.088 Å in 1b to RS-S ) 2.568 Å in 31b. The S-S bond length in 31b is still considerably shorter than the double van der Waals radius of sulfur (3.6 Å), implying a significant bonding interaction. If the bond energy of the residual S-S bond in 31b is taken as the energy difference between the triplet state and the lowest-lying ap-gauche biradical, then an S-S bond energy BDE of 7.0 kcal mol-1 results for 31b. The activation energy for the ring opening of 31b is calculated to be ∆Uqfw ) 10.6 kcal mol-1 or ∆Uqrv ) 3.3 kcal mol-1 for the reverse reaction. The latter value is in the range typical of C-C bond rotations in alkane derivatives. In addition, the C2symmetric gauche, gauche conformer of triplet biradical · S-(CH2)3-S · was also optimized at both the UB3LYP/ccpVTZ and ROHF-CCSD(T)/cc-pVTZ levels of theory. Why the energy of this conformer is significantly higher than the energy of ap-gauche conformer 37b is unclear at present. The results,

10.1021/jp108021k  2011 American Chemical Society Published on Web 01/27/2011

Triplet Excited States of Cyclic Disulfides

Figure 1. Calculated geometries, S-S distances, and relative energies for stationary points relevant to the triplet chemistry of 1b. Left: singlet ground state of 1b. Second from left: first triplet excited state of 1b. Second from right: transition structure for ring opening of the first triplet excited state of 1b. Right: triplet biradical in the ap-gauche conformation (37b). Bottom: triplet biradical in the C2-gauche-gauche conformation. Numbers: top, S-S distance optimized at the ROHF-CCSD(T)/cc-pVTZ level of theory (1b,31b, C2-symmetric gauche, gauche-biradical) or at the UB3LYP/cc-pVTZ level of theory (transition structure, C1symmetric ap-gauche biradical). Middle: Relative energies (in kcal mol-1) as calculated at the ROHF-CCSD(T)/cc-pVTZ//(U)B3LYP/ccpVTZ level of theory. Bottom (italic): Relative energies (in kcal mol-1) as calculated at the ROHF-CCSD(T)/cc-pVTZ (fully optimized) level of theory.

J. Phys. Chem. A, Vol. 115, No. 4, 2011 541 of 0.98/0.93 (Mulliken/Loewdin) at each S. An MO analysis of 31b reveals that the two singly occupied molecular orbitals have π* and σ* character (Figure 3), similar to the HOMO and LUMO of the ground-state molecule. Accordingly, 31b should be classified as a (π*, σ*) triplet excited state. In principle, a bond order of 1/2σ + 1/2π would result from such an electronic configuration. Whether it corresponds to an energy minimum on the potential energy hypersurface depends on factors such as the orbital overlap and ring strain. To extend this study of (π*, σ*) triplet excited states beyond lipoic acid and 1,2-dithiolane, we have examined a variety of substrates with two adjacent heteroatoms in a ring (fivemembered or six-membered ring). The triplet states investigated bear a variety of substituents, both at the four position of a fivemembered ring and in some cases directly at one of the heteroatoms, and also include benzoannulated systems. In terms of the computational methodology, we have employed the B3LYP and M05-2X DFT methods as well as CCSD(T) singlepoint energies based on B3LYP geometries. The basis set employed is cc-pVTZ in all calculations except for tellurium compound 1v, where the optimizations were done using the CEP-121G pseudopotential basis set and the CCSD(T) singlepoint energies using a def2-TZVP basis. For 1b, we have also included single-point energies calculated at the CCSD(T)/augcc-pVTZ//B3LYP/cc-pVTZ level of theory. Table 1 shows the results. In the case of 1a, we have restricted the conformational space of the pentanoic acid side chain by fixing an all-periplanar conformation.

Figure 2. Spin isodensity surface calculated (B3LYP/6-31G(d)) for 3 1b.

however, clearly indicate that ROHF-CCSD(T)/cc-pVTZ// (U)B3LYP/cc-pVTZ and ROHF-CCSD(T)/cc-pVTZ yield results that match each other within 0.6 kcal mol-1. Figure 2 shows a spin density isosurface of 31b, calculated at the B3LYP/6-31G (d) level of theory. According to the calculations (B3LYP/cc-pVTZ), almost the entire spin density is concentrated at the sulfur atoms, with a calculated spin density

Figure 3. Left: R-HOMO-1. Right: R-HOMO of 31b, as calculated at the UB3LYP/cc-pVTZ level of theory.

542

J. Phys. Chem. A, Vol. 115, No. 4, 2011

Ginagunta and Bucher

TABLE 1: Calculated Properties of Singlet Ground States, Triplet Excited States, Triplet and Singlet Biradicals, and the Transition States for Ring-Opening of Triplet Excited Statesa

Triplet Excited States of Cyclic Disulfides

J. Phys. Chem. A, Vol. 115, No. 4, 2011 543

TABLE 1: Continued

a Energies of triplet excited states (∆UT), energies of triplet and singlet biradicals (∆U T-BR and ∆U S-BR), energies for the transition states for ring opening of the triplet excited states (∆U (TS, T)), activation energies for the ring opening of triplet excited states to open-chain triplet biradicals (∆Uq), bond dissociation energies of triplet states (BDE), and the X-Y distance in the triplet excited and singlet ground states and point groups there of. Regular font: B3LYP. Italics: M05-2X. Bold: CCSD(T)//B3LYP. Bold italics: CCSD(T) fully optimized. Bold italics underlined: CCSD(T)/aug-cc-pVTZ//B3LYP. b In the case of unsymmetric chromophores (X * Y), there are two conformers of a biradical with one heteroatom gauche. The 1st number corresponds to the biradical with antiperiplanar X (Y gauche, 7), the 2nd number refers to the biradical with antiperiplanar Y (X gauche, 8) c In the case of unsymmetric chromophores (X * Y), there are two rotameric transition states. The 1st number refers to X moving, Y gauche (formation of 7), the 2nd number to Y moving, X gauche (formation of 8). d Energy difference (∆U) between the lower-energy gauche conformer of the triplet biradical and the triplet excited state. Positive numbers indicate that the triplet biradical is higher in energy than the triplet excited state. e PG ) point group. f n.c.: not calculated. g X-Y distance of the 2nd X-Y unit present in the molecule. h n.cv.: not converged. i n.m.: no minimum. j 2nd triplet excited state. k Singlet biradical l Closed-shell peroxide structure.

The data given in Table 1 can be analyzed according to several criteria, the most important being the triplet energies, the energy differences between the triplet states and the triplet biradicals, and the activation energies of ring opening for the triplet states. Important parameters vary across the range of compounds investigated and include the ring size (five vs six), remote substitution (R), nature of heteroatoms X and Y, substitution at Y, and effects of benzoannelation. Influence of the Nature of Heteroatoms X and Y. To have a triplet state with significant stabilization relative to an openchain biradical, two adjacent chalcogen atoms of the second long period or heavier are required. If one of the heavy chalcogens is replaced with an oxygen atom, an aminyl group, or a phosphinyl group, then this significantly reduces the stability of the triplet state. Compared to 1b as a reference system, the triplet energies of neutral heterocycles 1g, 1k, and 1m are higher by more than 10 kcal mol-1. The stability of the triplet excited state relative to that of the ring-opened triplet biradical is also greatly reduced. The X-Y bond dissociation enthalpy of the (π*, σ*) triplet excited state, which is defined as the stabilization relative to an open-chain (ap-gauche) triplet biradical, vanishes in systems 1g-1n, where Y ) NR, O, or PH. Because P- is isoelectronic with S, the observation that the (π*, σ*) triplet excited state is stabilized in 1o does not come as a surprise. If both heteroatoms are light chalcogens, as in peroxides 1v or 5f, then the (π*, σ*) triplet excited state no longer is a minimum.10 Heavy chalcogens selenium and in particular tellurium are predicted to stabilize the (π*, σ*) triplet excited state more efficiently than sulfur. This is revealed in the low calculated triplet energies of 1q (38.8 kcal mol-1) and 1w (29.1

kcal mol-1), but the calculated activation barriers for ring opening are also slightly higher for the (π*, σ*) triplet excited state of these selenium and tellurium compounds. With very few exceptions, the singlet biradicals are predicted to be generally equal in energy to the triplet biradicals. Influence of Substitution on Heteroatom Y. In the case of the pnictogen heterocycles, an additional substituent can be attached to the pnictogen atom. We have already discussed the fact that the introduction of a pnictogen atom as heteroatom Y dramatically lowers the stability of the (π*, σ*) triplet excited state. N substitution (R ) Ph or NMe2) lowers both the energy of the (π*, σ*) triplet state and the energy of the open-chain triplet biradical to a comparable degree. It therefore does not stabilize the (π*, σ*) state. Influence of Remote Substituents. Introducing a pair of alkyl or aryl substituents at the four position in the heterocyclic ring does not significantly affect the energy of the (π*, σ*) triplet excited state. It does, however, increase its barrier to ring opening. The effect is most pronounced for R ) Ph (1e), where the bulky phenyl substituents take up so much space that the distance between the sulfur centers is slightly compressed in the (π*, σ*) triplet excited state, thus slightly strengthening the (π*, σ*) sulfur-sulfur bond. The effect is known as the Thorpe-Ingold effect.11 Effects of Ring Size. Changing the ring size from a fivemembered ring to a six-membered ring is predicted to destabilize the (π*, σ*) triplet excited state to some degree. For example, when comparing 1b with 2a, the energy (M05-2X/cc-pVTZ) of the triplet excited state of six-membered ring 2a is predicted to be higher by almost 10 kcal mol-1, whereas the energy of

544

J. Phys. Chem. A, Vol. 115, No. 4, 2011

Ginagunta and Bucher

Figure 4. Optimized geometry (UM05-2X/cc-pVTZ) of triplet biradical 3 7f. The distances between the two sulfur atoms of the intact disulfide moiety and between one of the thiyl centers and a sulfur atom of the disulfide moiety are given. -1

the open-chain triplet biradical increases by only 7 kcal mol . As a result, the BDE of the S-S bond in 2a is reduced relative to that of 1b. The reason likely lies in the greater flexibility of the six-membered ring structure, which allows the ground state of the molecule to adopt a more favorable geometry than in case of the five-membered ring. The CSSC dihedral in groundstate 2a is calculated (M05-2X-cc-pVTZ) to be φ ) 58.3°. In 1b, the calculated CSSC dihedral is φ ) 46.0°. The deviation from the preferred dihedral (φ ) 90°) for a disulfide is therefore more pronounced for the five-membered ring. Because the energy of the triplet excited state of a disulfide is a function of the energy of the ground state as much as of the excited state, this results in a higher triplet excited state energy for the sixmembered ring. Effects of Spiroconjugation. Bis-disulfide and bis-diselenide 1f and 1s, respectively, contain a spiro linkage joining two fivemembered ring heterocycles. The properties of the lowest triplet excited states of 1f and 1s are very similar to the properties of the triplet states of simple heterocycles 1b and 1q. The spin density is therefore concentrated on just one dichalcogenide moiety. The S-S or Se-Se BDE of the triplet excited dichalcogenide moiety is lower than in the monocyclic molecules. This likely results from the fact that triplet (and singlet) open-chain biradicals 7f and 7s are stabilized by the interaction of one of the thiyl radical centers with the remaining disulfide moiety (RS-S ) 2.836 Å, see Figure 4). A sulfuranyl radical resulting from the addition of a thiyl radical to a disulfide had previously been observed in the pulse radiolysis of dimethyl disulfide.12 Effects of Benzoannulation. In most cases, benzoannulation is predicted to reduce the triplet energies of the (π*, σ*) triplet

Figure 5. Two highest occupied R-MOs of triplet 5e.

Figure 6. Optimized geometries (UM05-2X/cc-pVTZ) and calculated Mulliken spin densities of selected triplet excited states of derivatives of 5. Regular font: X-Y distance. Underlined: C-X or C-Y distance. Italics: Spin density at X or Y. In 5g, the P atom is found on the righthand side of the molecule.

excited states. In the case of six-membered ring disulfides 2a and 3a, the triplet excited state energy is reduced from a calculated 54.1 kcal mol-1 (2a) to 48.6 kcal mol-1 (3a). Because the energies of the open-chain triplet biradicals are not reduced by the same amount, the BDE of the S-S bond in the (π*, σ*) triplet excited states therefore increases. If the benzene rings are conjugated to the six-membered ring disulfide or diselenide chromophore, such as in 4a and 4b, the triplet excited state energy is slightly reduced relative to that of 3a or 3b. In the case of 4a, we could additionally optimize a second triplet state with a slightly larger S-S distance, which is slightly higher in energy than the (π*, σ*) T1 state. Perhaps because of the conjugation of the thiyl radical centers with the arene π systems, no true biradical geometry could be localized for either 4a or 4b.13 Peri-Naphthalene-Functionalized FiWe-Ring Heterocycles. In peri-substituted naphthalene derivatives 5, the rigidity of the molecular framework should prevent the existence of an equilibrium between (π*, σ*) triplet excited states and openchain triplet biradicals. Although we could optimize the triplet excited states in all cases, these triplet excited states have different character depending on the nature of heteroatoms X and Y. The lowest triplet excited states of 5a-5b (3B1) and 5c and 5g (3A′′) have (π*, σ*) character. They have typical X-Y and C-X/C-Y bond lengths (Figure 6) and rather low calculated triplet energies. The lowest triplet states of 5d, 5e, and 5h (3A′′), however, are characterized by very short C-Y

Triplet Excited States of Cyclic Disulfides SCHEME 1: Mesomeric Structures of Triplet 5e

SCHEME 2: Mesomeric Structures of Triplet 5g (T1)

(Y ) O, N-) bond lengths, which would be indicative of the prominent contribution of C,X-biradical mesomeric structures containing CdY (Scheme 1). A population analysis of triplet 5e reveals that the two singly occupied molecular orbitals are of σ* (HOMO-1) and π* (HOMO) character (Figure 5). Triplet 5e (likewise, 5d and T1 of 5h) should therefore be considered to be a σ,π-triplet biradical. In the case of 5b, 5g, and 5h, we could additionally locate triplet states that are higher in energy than the (π*, σ*) triplet excited states (5b and 5g) or the biradical (5h), with normal Se-Se, S-P, or S-N bond lengths. According to a population analysis, they are 3A1 (π, π*) (5b) or 3A′ (π, π*) (5h) triplet excited states or have 3A′ (π*, π*) character (5g).14 In the case of 5b and 5h, the energy of these T2 states is around 50 kcal mol-1, which is somewhat below the typical range for simple naphthalene derivatives. In the case of 5g, however, the 3A′ (π*, π*) T2 state is calculated to be almost degenerate with the 3 A′′ (π*, σ*) T1 state. The T1 state of 5g bears more than a full Mulliken spin unit at the phosphorus atom and could therefore also be described as a thiolate-functionalized triplet naphthyl phosphinidene (Scheme 2). This is consistent with the APT charge calculated for the sulfur atom in 5g (T1), which is -0.68 au (M052X/cc-pVTZ). Peroxide 5f is predicted not to be a closed-shell minimum structure at all.15 Optimizing 5f with an open-shell singlet wave function results in biradical geometry that is lower in energy than the closed-shell peroxidic geometry by 18.4 kcal mol-1,16 with the triplet state only marginally above it in energy. The T1 state of 5f is of the (π, π*) type (Supporting Information). The O-O distance calculated for 35f (RO-O ) 2.138 Å) is significantly shorter than the O-O distance in open-shell 15f (RO-O ) 2.812 Å). This indicates that unlike the open-shell singlet, the triplet state is not a pure biradical but still has some binding character between the oxygen atoms. Figure 6 shows the calculated structures and spin density values (UM05-2X/ccpVTZ) for the heteroatoms of the first excited triplet states of 5a-6.

J. Phys. Chem. A, Vol. 115, No. 4, 2011 545 The lowest triplet excited state of bis-disulfide 6, finally, is a 3B3u (π*, σ*) state. The increase in the S-S bond length and buildup of spin density at the sulfur atoms are approximately half of those for typical (π*, σ*) triplets. This is to be expected because the spin density is spread over twice the number of sulfur atoms. Whereas B3LYP and M05-2X agree on the optimized geometry, on the frontier orbitals, and on the spin distribution in this triplet state, they strongly disagree on its energy. In the absence of an experimental value or coupledcluster calculations, we have to leave the question about the triplet excited state energy of 6 unanswered. Kinetics of the Decay of 31a. In the preceding section, we have laid out our results on the triplet excited states of a series of heterocycles bearing two adjacent heteroatoms. We can now compare the results on triplet 1b with the known properties of the triplet state of 1a, which is known to have a lifetime τ ) 75 ns.8 A possible pathway for the deactivation of 31a would involve ring opening to triplet biradical 37a, followed by ISC yielding singlet biradical 17a and ring closure to ground-state 1a (Scheme 3). The rate-determining step of this sequence very likely would be the ring opening of 31a because both the ISC of a true triplet biradical such as 37a to a singlet biradical of almost equal energy and the ring closure of 17a can be expected to be very rapid. On the basis of the calculated thermochemical data for triplet 1b, we can utilize eq 1 to estimate a rate constant for the ring opening of 31b:

k)

H ) ( kTh )exp( ∆SR )exp(- RT q

q

(1)

The activation entropy is calculated to be practically zero (∆Sq ) -0.034 cal mol-1 K-1 (B3LYP)). The application of eq 1 yields rate constants of kB3LYP ) 1.5 × 103 s-1, kM05-2X ) 3.4 × 104 s-1, and kCCSD(T),aug-cc-pVTZ ) 1.1 × 104 s-1. For 1a, the corresponding estimated rate constants are kB3LYP ) 5.6 × 102 s-1 and kM05-2X ) 1.6 × 103 s-1, both of which are clearly much smaller than the experimental rate constant for the decay of 31a (kexp ) 1.3 × 107 s-1). Given the significant discrepancy between the calculated rate constant for ring opening and the experimental lifetime of 31a, it therefore appears unlikely that full ring opening to triplet biradical 37a is involved. However, ISC might not require full ring opening of the triplet state. A minimum-energy crossing point linking the triplet and singlet hypersurfaces could very well be close to the reaction coordinate of the ring opening of 31a but prior to the transition state. Using Harvey’s search routine for minimum-energy crossing points (MECP),17 we could localize such an MECP for 31b with an S-S distance of RSS ) 3.09 Å (B3LYP/cc-pVTZ) (Figure 7). Its electronic energy is higher than that of the triplet state by 7.2 kcal/mol. Entering the calculated enthalpies and entropies into eq 1, we obtain an estimate of the rate constant for the ISC of 31b of kISC ) 3.1 × 108 s-1. Although this is faster than the experimental value of kexp ) 1.3 × 107 s-1, it is by far closer to experiment than the values obtained on the basis of the assumption of complete ring opening.

SCHEME 3: Biradical Pathway for Deactivation of Triplet Lipoic Acid (R ) (CH2)4COOH)

546

J. Phys. Chem. A, Vol. 115, No. 4, 2011

Ginagunta and Bucher References and Notes

Figure 7. Optimized geometry (B3LYP/cc-pVTZ) of the minimumenergy crossing point linking the T1 and S0 states of 1b. RSS is calculated to be 3.09 Å.

Conclusions Heterocycles bearing two adjacent heteroatoms are predicted to have the lowest triplet excited states of the (π*, σ*) type. This applies not only to previously studied lipoic acid 1a and its amide but also to a range of other heterocycles investigated in this work. For the stability of the (π*, σ*) triplet states, the presence of two heavy chalcogens (S, Se, or Te) appears to be ideal, and five-membered-ring geometry is also favorable. Deactivation of triplet lipoic acid likely does not occur via ring opening to a true triplet biradical but by intersystem crossing at a geometry with an S-S distance of around 3.09 Å. Computational Methodology. DFT calculations were performed using the Gaussian 09 suite of programs.18 We employed the standard B3LYP method19,20 and the M05-2X method.21 Coupled-cluster single-point energies were calculated using either ORCA22,23 or MOLPRO24 software. Coupled-cluster optimizations were done by employing MOLPRO. The spin isodensity surface shown in Figure 2 was obtained using Spartan08.25 Throughout the study, we generally employed the Dunning cc-pVTZ basis set.26 Tellurium compound 1v was optimized using a CEP 121 pseudopotential basis,27,28 followed by CCSD(T)/def2-TZVP29 single-point energies. All stationary points optimized by DFT methods were fully characterized by performing vibrational analyses. Singlet biradicals were optimized by employing a broken-symmetry wave function (G09 keywords guess ) (mix,always)). The search for a minimumenergy crossing point linking the singlet and triplet hypersurfaces in 1b was conducted by employing ORCA software. ORCA was also used to calculate Loewdin spin densities for 31b. Acknowledgment. This work was performed as part of the Glasgow Centre for Physical Organic Chemistry, funded by the EPSRC. We gratefully acknowledge this funding. Supporting Information Available: Cartesian coordinates and energies of optimized stationary points. This material is available free of charge via the Internet at http://pubs.acs.org.

(1) Scott, B. C.; Aruoma, O. I.; Evans, P. J.; O’Neill, C.; van der Vliet, A.; Cross, C. E.; Tritschler, H.; Halliwell, B. Free Radical Res. 1994, 20, 119. (2) Packer, L.; Witt, E. H.; Tritschler, H. J. Free Radical Biol. Med. 1995, 19, 227. (3) Biewenga, G. P.; Haenen, G. R. M. M.; Bast, A. Gen. Pharmacol. 1997, 29, 315. (4) Bilska, A.; Włodek, L. Pharmacol. Rep. 2005, 57, 570. (5) Ghibu, S.; Richard, C.; Vergely, C.; Zeller, M.; Cottin, Y.; Rochette, L. J. CardioVasc. Pharmacol. 2009, 54, 391. (6) Lu, C.; Bucher, G.; Sander, W. ChemPhysChem 2004, 5, 47. (7) Lu, C.; Bucher, G.; Sander, W. ChemPhysChem 2004, 5, 399. (8) Bucher, G.; Lu, C.; Sander, W. ChemPhysChem 2005, 6, 2607. (9) Bucher, G. Unpublished work. (10) Independent of the method used, attempted optimizations of the triplet state of 1v resulted in the optimization of a triplet gauche, gauche dioxy biradical. (11) Beesley, R. M.; Ingold, C. K.; Thorpe, J. F. J. Chem. Soc., Trans. 1915, 107, 1080. (12) Bonifacˇic´, M.; Asmus, K.-D. J. Phys. Chem. 1984, 88, 6286. (13) Attempts to localize a true triplet biradical at a dihedral between the arene moieties of 90° were not met with success. (14) The HOMO in ground-state 5g has π* character. (15) Sanz, P.; Ya´nez, M.; Mo´, O. ChemPhysChem 2003, 4, 830. (16) A value of S2 ) 0.89 indicates significant biradical character of 5f. (17) Harvey, J. N.; Aschi, M.; Schwarz, H.; Koch, W. Theor. Chem. Acc. 1998, 99, 95. (18) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, ¨ .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, O ReVision A.02; Gaussian, Inc.: Wallingford, CT, 2009. (19) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (20) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785. (21) Zhao, Y.; Schultz, N. E.; Truhlar, D. G. J. Chem. Theory Comput. 2006, 2, 364. (22) Neese, F.; Wennmohs, F.; Hansen, A.; Grimme, S. Acc. Chem. Res. 2009, 42, 641. (23) Neese, F.; Wennmohs, F. ORCA, version 2.8-00; Universita¨t Bonn, 2009. (24) MOLPRO, version 2008.1; University College Cardiff Consultants: Cardiff, U.K., 2008. (25) Spartan 08; Wavefunction Inc.: Irvine CA, 2008. (26) Kendall, R. A.; Dunning, T. H. Jr. J. Chem. Phys. 1992, 96, 6796. (27) Stevens, W. J.; Basch, H.; Krauss, M. J. Chem. Phys. 1984, 81, 6026. (28) Stevens, W. J.; Krauss, M.; Basch, H.; Jasien, P. G. Can. J. Chem. 1992, 70, 612. (29) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297.

JP108021K