Computational Investigation of the Influence of Halogen Atoms on the

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Computational Investigation on the Influence of Halogen Atoms on the Photophysical Properties of Tetraphenylporphyrin and Its Zinc (II) Complexes Bruna Clara De Simone, Gloria Mazzone, Nino Russo, Emilia Sicilia, and Marirosa Toscano J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.8b00414 • Publication Date (Web): 19 Feb 2018 Downloaded from http://pubs.acs.org on February 22, 2018

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The Journal of Physical Chemistry

Computational Investigation on the Influence of Halogen Atoms on the Photophysical Properties of Tetraphenylporphyrin and its zinc (II) complexes Bruna C. De Simone, Gloria Mazzone*, Nino Russo*, Emilia Sicilia and Marirosa Toscano Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Rende (CS), Italy

ABSTRACT How the tetraphenylporphyrin (TPP) and its zinc (II) complex (ZnTPP) photophysical properties (adsorption energies, singlet-triplet energy gap and spin orbit coupling contributions) can change due to the presence of an increasing number of heavy atoms in their molecular structures has been investigated by means of density functional theory and its time dependent formulation. Results show as the increase of the atomic mass of the substituted halogen strongly enhances the spin-orbit coupling values allowing a more efficient singlet-triplet intersystem crossing. Different deactivation channels have been considered and rationalized on the basis of El-Sayed and Kasha rules. Most of the studied compounds possess the appropriate properties to generate cytotoxic singlet molecular oxygen (1∆g) and, consequently, they can proposed as photosensitizers in photodynamic therapy.

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INTRODUCTION Photophysical properties change of an excited system due to the presence of an atom with high atomic number in its molecular structure (the so-called heavy atom effect), is well documented since 1952 in the pioneering work of McClure1 in which it has observed a significant decrease in the phosphorescence lifetime in a series of aromatic compounds containing an atom with a high atomic number. A series of further investigations have deepened the knowledge of this phenomena whose rationalization has been firstly proposed by Kasha2 and El-Sayed.3 The variation in spin-orbit coupling resulting from the presence of a heavy atom in the molecular structure is the main responsible of the differences observed in the photophysical properties. Nowadays this subject is an important topic in different areas of research since it can determine and modulate the optical properties of a given chemical systems. In particular, the magnitude of spin-orbit coupling constant (SOC) can regulate the occurrence or not of the electronic transition from a singlet to a triplet state, formally “spin forbidden” owing to the orthogonality of the spin functions. The presence of a heavy atom directly bonded to the chromophore gives rise to a generally classified internal heavy atom effect, while when the atom with high atomic weight is close to the chromophore an external heavy atom effect is generated. The exact mechanism of this phenomenon has not been fully clarified yet. In the case of the internal heavy atom effect, the heavy atom presence can enhance the singlettriplet mixing already present in the molecule or introduce new perturbing states. On the basis of El-Sayed work3 a change in the orbital nature in going from singlet to triplet states sensibly enhances the SOCs. The charge transfer induced by the heavy atom, is considered as the preferred mechanism responsible of the external heavy atom effect. The intersystem crossing (ISC) process caused by the heavy atom effect has a great importance in many photochemical and photophysical events (e.g. photocatalytic organic reactions, triplet-triplet annihilation, upconversion, and singlet oxygen generation). Of particular interest are the photoreactions involved in photodynamic therapy (PDT) that, in the last two decades, has been clinically approved as a minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells.4-8 PDT consists of three essential components: photosensitizer, light, and oxygen. None of these is individually toxic, but together they initiate a series of photochemical processes (Type II reactions) that ultimately lead to the generation of a highly reactive singlet molecular oxygen, 1∆g state, that rapidly causes significant toxicity and cell death via apoptosis or necrosis. In order to produce this potent cytotoxic agent the photosensitizer must possess a series of peculiar photophysical properties: i) adsorbtion in the NIR region of the spectrum in order to deeply penetrate into the target tissues (500-800 nm); ii) an energy gap 2 ACS Paragon Plus Environment

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between its ground state and its first excited triplet one (∆S1-T1) sufficiently large (up to 0.98 eV) to ensure the excitation of molecular oxygen from 3Σg ground to singlet excited 1∆g state; iii) low fluorescence yield and efficient energy transfer from a singlet to a triplet state (Sn→Tn) via an intersystem spin crossing. These properties are mandatory to propose a new molecule as photosensitizer in PDP, but are not sufficient. In fact, the drug must be also inert in the dark, soluble in water environment, photostable and it should not exhibit tendency to aggregate.4 In a series of previous works, we have shown as the Density Functional Theory in its timedependent formalism is able to correctly reproduce the photophysical properties of a wide range of molecular systems including dyes proposed or designed as potential photosensitizers in PDT.9-15 In this work, we will show as the presence of halogen atoms in the skeleton of the tetraphenylporphyrin (TPP) and its zinc (II) complex (ZnTPP) (reported in Scheme 1) is important in order to increase the ISC and, consequently, to produce cytotoxic excited molecular oxygen in high yield.

i)

b

c R

R N d

ii)

a N

M

N

h

e

N R

R f

g

iii)

Cmpd H2TPP H2TPPCl4 H2TPPF8 H2TPPCl8 H2TPPI8 ZnTPPF4 ZnTPPCl4 ZnTPPBr4 ZnTPPF8 ZnTPPCl8 ZnTPPBr8 ZnTPPI8 ZnTPOF4 ZnTPOCl4 ZnTPOBr4 ZnTPOI4

M 2H 2H 2H 2H 2H Zn Zn Zn Zn Zn Zn Zn Zn Zn Zn Zn

R H H H H H H H H H H H H OCH3 OCH3 OCH3 OCH3

a H Cl F Cl I F Cl Br F Cl Br I H H H H

b H H F Cl I H H H F Cl Br I F Cl Br I

c H Cl F Cl I F Cl Br F Cl Br I F Cl Br I

d H H F Cl I H H H F Cl Br I H H H H

e H Cl F Cl I F Cl Br F Cl Br I H H H H

f H H F Cl I H H H F Cl Br I F Cl Br I

g H Cl F Cl I F Cl Br F Cl Br I F Cl Br I

h H H F Cl I H H H F Cl Br I H H H H

Scheme 1. Schematic representation of the three classes of compounds investigated.

COMPUTATIONAL DETAILS All the geometry optimizations have been performed without symmetry constraints at density functional level of theory by using the Gaussian 09 code.16 The M06 exchange correlation functional17 coupled with the 6-31+G* basis set for all the atoms have been chosen excepts for I, for which the SSD pseudopotential18 has been employed. The vibrational analysis confirmed that all the intercepted structures are real minima. TD-DFT has been used to compute the electronic excitations 3 ACS Paragon Plus Environment


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including solvent effects by means of integral equation formalism polarizable continuum model (IEFPCM).19,20 The choice of benzene as solvent (ε = 2.27) has been dictated by the presence in literature of the experimental UV-Vis spectra in this medium.21,22 Spin−orbit matrix elements have been computed by using the quadratic-response TD-DFT approach, as implemented in the Dalton program code23 by using the Spin–Orbit Coupling Operators for Effective Core Potentials with the effective nuclear charge24 for systems containing iodine atoms, while atomic-mean field approximation25 has been used in the other cases. For this purpose, B3LYP functional26,27 in conjunction with cc-pVDZ basis set has been used for all the atoms except iodine for which the coupled pseudopotential17 has been considered. Following the Fermi Golden Rule,28 the intersystem

T and the crossing (ISC) kinetics is directly related to the spin-orbit matrix elements S H

Franck-Condon weighted density of states FCWD throughout the following expression:

=

ℏ

T × FCWD S H

The Spin orbit coupling constant have been computed by using the following formula

#& " ' 〉 ; / = 0, 1, 2 = 〈"#$ % (,* ,

#& is the spin–orbit Hamiltonian. where %

In the framework of Marcus-Levich-Jortner theory28 the FCWD is proportional to the exponential factor: 345 ∝ 708 9−

;∆=#>' ? D 4A B C

where λ is the Marcus reorganization energy and ∆E is the difference between the energies of singlet and the triplet states at their equilibrium geometry. Since the estimation of FCWD is generally highly expensive, we have computed only the spin-orbit matrix elements and the vertical singlet-triplet energy gaps in order to predict the deactivation pathways that lead to production of 1

∆g state of molecular oxygen. The correctness of this procedure is supported by previous

theoretical studies 9-15,29,30 on a large series of compounds that can act as photosensitizers in PDP.


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RESULTS AND DISCUSSION The investigated molecular systems can be divided into three groups, in which the halogens atoms (4 or 8) are placed in different amount in the orto positions of i) phenyl rings of the naked H2TPP, ii) phenyl rings of Zn-TPP complex, iii) phenyl rings of Zn-TPP complexes in which a meta position of each ring is occupied by the electron donor methoxy group. The computed TDDFT singlet and triplet excitation energies together with the orbital transitions and available experimental spectroscopic data are collected in Tables 1 and 2. In the case of H2TPP and its halogenated derivatives (group i)) the lowest energy absorptions, S1 and S2, have small values of oscillator strength and the first most intense peak is given by the absorption leading to the S3 population (see Table 1). The presence of halogens significantly affects the nature of the transitions. In fact, while in the H2TPP the excitations to S1 and S2 are due to the H→L and H→L+1 transitions, respectively, in all its halogenated derivatives excitations occur between H→L+1 (S1) and H→L (S2) orbitals. In all the ZnTPP halogenated derivatives (groups ii) and iii)) we found that the lowest excitation energy, characterized by a weak oscillator strength value, is double degenerated (S1 and S1’) in agreement with previous studies.31-33 They are generated by H→L+1 and H→L transitions with percentages higher than 50% in compounds with 4 halogen atoms and slightly less than 50% in those containing 8 halogens. There are other two degenerate transitions (leading to S2 and S2’) that show larger oscillator strength. In all molecules they arise from H-1→L and H-1→L+1 transitions, respectively. For these systems the energy degeneracy observed for the singlet states occurs also for the lowest excited triplet states (as shown in Table 2). As previously reported for other TPPs,31-33 the absorption falls in the low region of the therapeutic window, considering that in all cases S1 or both S1 and S2 excited states show very small oscillator strengths. Looking at the available experimental UV-Vis spectra we found a satisfactory agreement between measured21,22 and computed excitation energies. The computed singlet energies result slightly overestimated, with an average error of about 0.2 eV. The experimental information on triplet states are limited to the lowest lying state (T1) of four compounds investigated here (labelled as H2TPP, ZnTPPF8, ZnTPPCl8, ZnTPOBr4). The comparison of T1 excitation energy for these compounds shows also in this case an average error of less than 0.2 eV. It is worthy of note that the energy gap between the ground and the low lying triplet excited state ∆ES0-T1 assumes values higher than the energy requested (0.98 eV) to excite the molecular oxygen from its triplet ground state (3Σg) to the singlet one (1∆g) for all the investigated systems and consequently all should be able to produce the key cytotoxic agent for PDT. Since the efficiency of the ISC between two states depends on the spin-orbit coupling values, we have computed all the plausible SOCs between the different states as 5 ACS Paragon Plus Environment


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reported in Tables 3 and 4 for the non metallated H2TPP and metallated ZnTPP derivatives, respectively.

Table 1. M06/6-31+G* main vertical singlet excitation energies ∆E (eV), oscillator strengths f, wavelength λ (nm) and MO contribution to the transitions (%) for all the investigated compounds computed in benzene solvent. Excited state λtheo ∆Etheo S1 593 2.09 S2 562 2.21 S3 414 2.99 S1 577 2.15 H2TPPCl4 S2 545 2.27 S3 408 3.03 S1 579 2.14 H2TPPF8 S2 548 2.26 S3 411 3.01 S1 579 2.14 H2TPPCl8 S2 548 2.26 S3 411 3.01 S1 593 2.09 H2TPPI8 S2 563 2.20 S3 428 2.90 ii) ZnTPPF4 S1(S1') 549 2.26 S2(S2') 404 3.07 S1(S1') 545 2.28 ZnTPPCl4 S2(S2') 400 3.10 S1(S1') 547 2.26 ZnTPPBr4 S2(S2') 403 3.08 S1(S1') 546 2.27 ZnTPPF8 S2(S2') 400 3.10 S1(S1') 547 2.27 ZnTPPCl8 S2(S2') 401 3.09 S1(S1') 553 2.24 ZnTPPBr8 S2(S2') 408 3.04 S1(S1') 561 2.21 ZnTPPI8 S2(S2') 418 2.96 iii) ZnTPOF4 S1(S1') 551 2.25 S2(S2') 407 3.04 S1(S1') 544 2.28 ZnTPOCl4 S2(S2') 400 3.10 S1(S1') 547 2.27 ZnTPOBr4 S2(S2') 403 3.08 S1(S1') 550 2.26 ZnTPOI4 S2(S2') 407 3.05 a. ref 22; b. ref 21 i)

Cmpd H2TPP

f 0.044 0.069 1.636 0.005 0.007 1.434 0.002 0.012 1.488 0.001 0.006 1.389 0.002 0.010 1.238 0.005 1.740 0.001 1.680 0.001 1.640 0.000 1.725 0.001 1.628 0.000 1.547 0.000 1.395 0.005 1.706 0.001 1.700 0.001 1.676 0.001 1.621

Transition ∆Eexp H→L, 66% 1.91a H→L+1, 65% H-1→L+1, 64% H→L+1, 55% 1.89b H→L, 52% H-1→L, 53% H→L+1, 56% 1.89b H→L, 55% H-1→L, 53% H→L+1, 56% 1.88b H→L, 54% H-1→L, 54% H→L+1, 58% H→L, 56% H-1→L, 56% H→L+1, 51% (H→L, 52%) H-1→L, 34% (H-1→L+1, 34%) H→L+1, 44% (H→L, 44%) H-1→L, 44% (H-1→L+1, 44%) H→L+1, 39% (H→L, 39%) H-1→L, 51% (H-1→L+1, 51%) H→L, 44% (H→L+1,44%) 2.19b H-1→L, 44% (H-1→L+1, 44%) H→L, 51% (H→L+1, 51%) 2.10b H-1→L+1,28% (H-1→L, 28%) H→L+1, 28% (H→L, 28%) H-1→L+1, 46% (H-1→L, 46%) H-1→L+1, 45% (H-1→L, 45%) H→L+1, 50% (H→L, 50%) H→L+1, 42% (H→L, 42%) H-1→L, 30% (H-1→L+1, 30%) H→L+1, 43% (H→L, 43%) H-1→L, 49% (H-1→L+1, 49%) H→L, 44% (H→L+1, 44%) 2.01b H-1→L+1, 32% (H-1→L, 32%) H→L+1, 43% (H→L, 43%) H-1→L, 50% (H-1→L+1, 50%)

As a general trend, we found that the magnitude of the SOCs increases as a function of the atomic mass of the halogen. This is partially due to the so-called internal heavy atom effect that is directly 6 ACS Paragon Plus Environment

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proportional to the atomic number (Z4) and inversely related to the mean cubic radial distribution (r3

) of the electron.

Table 2. M06/6-31+G* main vertical triplet electronic energies ∆E (eV) and MO contribution to each transition (%) for all the investigated compounds computed in benzene solvent. Cmpd H2TPP

Excited state ∆Etheo i) T1 1.24 T2 1.61 T3 1.94 T4 1.99 T1 1.24 H2TPPCl4 T2 1.68 T3 1.93 T4 1.95 T1 1.25 H2TPPF8 T2 1.71 T3 1.90 T4 1.91 T1 1.20 H2TPPCl8 T2 1.67 T3 1.90 T4 1.91 T1 1.15 H2TPPI8 T2 1.63 T3 1.86 T4 1.86 ii) ZnTPPF4 T1(T1') 1.57 T2(T2') 1.97 T1(T1') 1.57 ZnTPPCl4 T2(T2') 1.97 T1(T1') 1.56 ZnTPPBr4 T2(T2') 1.96 T1(T1') 1.58 ZnTPPF8 T2(T2') 1.95 T1(T1') 1.54 ZnTPPCl8 T2(T2') 1.94 T1(T1') 1.52 ZnTPPBr8 T2(T2') 1.93 T1(T1') 1.50 ZnTPPI8 T2(T2') 1.90 iii) ZnTPOF4 T1(T1') 1.57 T2(T2') 1.96 T1(T1') 1.57 ZnTPOCl4 T2(T2') 1.97 T1(T1') 1.56 ZnTPOBr4 T2(T2') 1.96 T1(T1') 1.55 ZnTPOI4 T2(T2') 1.95 a. ref 21

Transition H→L+1, 80% H→L, 96% H-1→L, 80% H-1→L+1, 96% H→L, 75% H→L+1, 86% H-1→L+1, 71% H-1→L, 86% H→L, 73% H→L+1, 80% H-1→L, 80% H-1→L+1, 71% H→L, 77% H→L+1,86% H-1→L+1, 73% H-1→L, 86% H→L, 76% H→L+1, 85% H-1→L+1, 72% H-1→L, 85% H→L, 69% (H→L+1, 69%) H-1→L, 67% (H-1→L+1, 67%) H→L, 69% (H→L+1, 69%) H-1→L, 59% (H-1→L+1, 59%) H→L, 71% (H→L+1,71%) H-1→L, 71% (H-1→L+1, 71%) H-1→L+1, 44% (H-1→L, 44%) H→L, 63% (H→L+1, 63%) H-1→L, 59% (H-1→L+1, 59%) H→L, 65% (H→L+1, 65%) H-1→L, 61% (H-1→L+1, 61%) H→L, 65% (H→L+1, 65%) H-1→L, 60% (H-1→L+1, 60%) H→L, 65% (H→L+1, 65%) H→L, 65% (H→L+1, 65%) H-1→L, 64% (H-1→L+1, 64%) H→L, 69% (H→L+1, 69%) H-1→L, 71% (H-1→L+1, 71%) H→L, 44% (H→L+1, 44%) H-1→L, 71% (H-1→L+1, 71%) H→L, 70% (H→L+1, 70%) H-1→L, 66% (H-1→L+1, 66%)

∆Eexpa 1.43

1.69 1.65

1.66



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In addition, as previously mentioned, the El-Sayed’s rule states that the significant increase in SOC values is ascribable to the change in the orbitals composition of the states involved in the nonradiative intersystem spin crossing process. From the inspection of molecular orbital composition for the states involved in both S0→S1 and S1→T1 transitions, the nature of the transitions changes from π-π* to π-n* and the n contribution to the molecular orbital increases as a function of the halogen atom mass. Table 3. Spin orbit coupling constant SOCij (cm-1) calculated according to equation (2) between low-lying singlet (Si with i=1-3) and triplet (Tj with j=1-4) excited states calculated at B3LYP/cc-pVDZ//M06/6-31+G* for compounds belonging to group i). Vertical energy gaps ∆Eij between the involved states are reported in eV. H2TPP H2TPPCl4 H2TPPF8 H2TPPCl8 H2TPPI8 SOCi,j ∆Eij SOCi,j ∆Eij SOCi,j ∆Eij SOCi,j ∆Eij SOCi,j ∆Eij S1-T1 9·10-2 0.85 2.80 0.91 3.1·10-1 0.89 6.79 0.94 310.98 0.94 S1-T2 0 0.48 1·10-2 0.47 1·10-2 0.43 1·10-2 0.47 2.5·10-1 0.46 -2 -1 S1-T3 1·10 0.15 1.29 0.22 1.2·10 0.24 2.81 0.24 148.84 0.23 S1-T4 0 0.10 1·10-2 0.20 1·10-2 0.23 4·10-2 0.23 1.24 0.23 S2-T1 0 0.97 0 1.03 1·10-2 1.01 1·10-2 1.06 2.3·10-1 1.00 -2 -1 S2-T2 8·10 0.60 2.60 0.59 3.1·10 0.55 6.47 0.59 321.64 0.53 S2-T3 0 0.27 1·10-2 0.34 2·10-2 0.36 7·10-2 0.36 2.00 0.30 -2 -1 S2-T4 2·10 0.22 2.00 0.32 2·10 0.35 4.45 0.35 244.39 0.29 S3-T1 1.1·10-1 1.75 6.9·10-1 1.79 5·10-2 1.76 2.03 1.81 270.34 1.75 -2 -2 S3-T2 1·10 1.38 1·10 1.35 4·10-2 1.30 1·10-2 1.34 7.1·10-1 1.27 S3-T3 2.3·10-1 1.05 8·10-1 1.10 3.2·10-1 1.11 1.90 1.11 335.80 1.04 S3-T4 0 1.00 1·10-2 1.08 4·10-2 1.10 3·10-2 1.10 3.37 1.04 Table 4. Spin orbit coupling constant SOCij (cm-1) calculated according to equation (2) between low-lying singlet (Si with i=1-3) and triplet (Tj with j=1-4) excited states calculated at B3LYP/cc-pVDZ//M06/6-31+G* for compounds belonging to groups ii) and iii). Vertical energy gaps ∆ESiTj between the involved states are reported in eV. S1-T1 ZnTPPF4 ZnTPPCl4 ZnTPPBr4 ZnTPPF8 ZnTPPCl8 ZnTPPBr8 ZnTPPI8 ZnTPOF4 ZnTPOCl4 ZnTPOBr4 ZnTPOI4

SOC 1.79 1.43 21.60 1.53 5.71 48.77 310.03 1.64 5·10-1 2.20 112.71

S1-T2 ∆E 0.69 0.71 0.70 0.69 0.73 0.72 0.71 0.68 0.71 0.71 0.71

SOC 2.2·10-1 3.2·10-1 3.47 2.1·10-1 8.8·10-1 11.66 60.85 5.2·10-1 3.7·10-1 6.36 15.45

S2-T1 ∆E 0.29 0.31 0.30 0.32 0.33 0.31 0.31 0.29 0.32 0.31 0.71

SOC 4.4·10-1 4.2·10-1 5.90 2·10-1 9·10-1 12.71 41.47 8·10-2 1.76 9.98 145.70

S2-T2 ∆E 1.50 1.53 1.52 1.52 1.55 1.52 1.46 1.47 1.53 1.52 1.50

SOC 5.3·10-1 1.66 7.51 8.5·10-1 2.20 31.32 406.58 1.1·10-1 1.25 11.31 182.83

∆E 1.13 1.13 1.12 1.15 1.15 1.11 1.06 1.08 1.13 1.12 1.10

In particular, the T1 orbital composition includes the lone pairs of the halogens and their contribution becomes dominant in the case of the iodine-containing compounds. This behavior well accounts for the drastic enhancement of the SOCs in all iodine-substituted compounds (see Tables 3 8 ACS Paragon Plus Environment

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and 4). However, taking as reference the SOC value calculated for the Foscan34 (SOCS1-T1= 0.24 cm-1), an effective photosensitizer clinically approved in PDT, it appears evident from Tables 3 and 4 that there are values of spin-orbit coupling for various ISC processes that far exceed the reference value. For this reason, in principle, different possible deactivation pathways could be considered viable and we have taken into account the most plausible ones. As shown in Table 1, for H2TPP halogenated derivatives (group i)) three singlet states could be populated upon irradiation, with the two lowest ones (S1 and S2) which present small oscillator strength. Therefore, the following paths have been considered possible: G

JK

a? SF →SI LM TN G

JK

JK

b? SF →SI → S LMTN G

JK

JK

JK

c? SF →SI → S → Q LM TN, with j=1-4

Table 3 shows that the highest SOC values are found for the ISC involving S1-T1, S1-T3, S2-T2, S2T4, S3-T1 and S3-T3 states. The increasing of substituted halogens number from 4 to 8 contributes to raising the values of the SOCs (see chlorine-containing systems). Going from fluorine to iodine we underline that the bigger the atomic size of the halogen atom the larger the SOC values. In particular, iodine-containing compounds show values greater of more than two orders of magnitude with respect to fluorine-containing compounds. For metallated systems of group ii) and iii) the irradiation leads to the population of S2 excited state, then the following decay route can be considered: G

JK

JK

d? SF →S → SQ LM TN, with j=1,2

For molecules belonging to the group ii), the SOCs computed for S1-T1 and S2-T2 intersystem

crossing processes are the highest ones and in ZnTPPI8 assume very large values (310.03 and 406.58 cm-1, respectively). The expected trend depending on the increase of the atomic number is observed also in these cases. Indeed, the SOCs obtained for brominated compound ZnTPPBr8 assume values one order of magnitude smaller than those computed for iodine-containing compound ZnTPPI8. The feasible intersystem spin crossing pathways for the population of the lowest triplet states can be rationalized on the basis of the Kasha rule, which states that, in a given spin manifold, the transition Si→S1(with i>1) should be very fast and triplet state population should start from the lowest singlet exited state (S1). Consequently, in all cases the favored process implies, after absorption, the fast decay via IC in the low-lying excited singlet state with subsequent intersystem spin crossing to the triplet states with energy lower than S1. In all the studied compounds, the SOCS1-T1 have great 9 ACS Paragon Plus Environment


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values that should ensure an efficient S1-T1 intersystem crossing. However, looking at both SOC values and vertical energy gaps collected in Table 3 for compounds belonging to group i) both pathway b, in which the ISC is assumed to occur between S2 and T4, and pathway c, involving S1-T3 ISC, seem to be the equally probable. While the preferred deactivation pathway involving the S1-T1 ISC appears more pronounced for metallated compounds, as, though both SOCS1-T1 and SOCS2-T2 are of the same order of magnitude, the energy gap S2-T2 in all cases is greater than the energy gap S1-T1, suggesting the S1-T1 ISC process as favored. Due to the availability of KISC measured for a series of treated compounds21 we can ascertain the reliability of theoretical predictions by comparing the kinetic constant with the computed SOC values. On the basis of considerations just described, we reported in Figure 1 the available experimental information compared with SOCS1-T1.

Figure 1. Computed SOCs (cm-1) for S1–T1 and for S2–T1 (ZnTPOBr4) radiationless transitions and measured (from ref. 21) KISC for some of the investigated systems.

The comparison is quite satisfactory and the theoretical behavior (black squares) well agrees with the experimental profile (red circles) except for the ZnTPPI8 compound. However, if we consider for this system the SOCS2-T1 (blue triangle) the qualitative comparison between theory and 10 ACS Paragon Plus Environment

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experiment become very satisfactory. These results confirm the importance to consider all the plausible ISC processes in discriminating between all the possible deactivation pathways of the state populated upon irradiation.

CONCLUSIONS We have reported here a DFT-based theoretical investigation to establish whether the photophysical properties of a series of polyhalogenated tetraphenylporphyrins and their zinc (II) complexes can be affected by the presence of halogen atoms in the TPP skeleton and to verify if these compounds can be proposed as photosensitizers in PDT. Excitation energies, singlet-triplet energy gaps and spin orbit coupling constants between all the plausible excited states have been determined for all the halogenated compounds in which four or eight halogen atoms (F, Br, I) have been substituted in

orto positions of phenyl rings of TPP. Results clearly show that the presence of the heavy atoms slightly (few nanometers) affects the absorption wavelengths, with Q band falling in the low region of the therapeutic window. However, the computed singlet and triplet excitation energies well compare with the available experimental counterparts, with an average error of no more than 0.2 eV. For all the investigated compounds the T1 state has been found lying at energy higher than that required to excite molecular oxygen from its triplet ground state to the singlet excited one (0.98 eV), this means that the triplet state has enough energy to promote the 1O2 photosensitization. As expected, the computed SOCs consistently increase with the halogen atom mass, reaching the highest values for iodine-containing TPP, ensuring efficient intersystem crossing for different decay routes. The bigger the halogen atomic size the higher the SOC values, because the presence of halogen atoms effectively affects the orbitals composition, especially in the triplet state, for which the contribution of halogen atom lone pairs increases with atomic mass of halogens, implying that the ISC process occurs between states with π-π* character (singlets) and states with π-n* character (triplets), following the El-Sayed’s rule. On the basis of both SOCs and ∆ΕS-T values different deactivation channels have been hypothesized and the most probable appeared those in which the S1-T1 ISC process is involved. Putting together all the PDT-related photophysical properties, both bromine- and iodine-containing systems could be proposed as potential photosensitizers for PDT application.



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ASSOCIATED CONTENT Supporting Information. Cartesian coordinates of optimized structures.

AUTHOR INFORMATION Corresponding Authors *(G.M.). E-mail: [email protected]. * (N. R.). E-mail: [email protected].

ACKNOWLEDGMENT The authors thanks Università della Calabria for financial support.

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Computational Investigation of the Influence of Halogen Atoms on the

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