Interplay between Conjugation and Size-Driven Delocalization Leads

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Interplay between Conjugation and Size-Driven Delocalization Leads to Characteristic Properties of Substituted Thymines Meghna A Manae, and Anirban Hazra J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b08566 • Publication Date (Web): 29 Sep 2017 Downloaded from http://pubs.acs.org on October 5, 2017

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The Journal of Physical Chemistry

Meghna A. Manae* and Anirban Hazra* Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India ABSTRACT: Substituted thymines, where oxygen is replaced by sulfur or selenium affect a variety of functions in biological systems and are prospective phototherapeutic agents. In this study, we show that an interplay between two types of delocalization, one due to conjugation and the other owing to the varying size of the substituted atom, leads to distinct absorption spectra and electrophilic sites in substituted thymines. This result is supported by ab initio quantum chemical calculations and a simple particle-in-a-box model. The model explains the unexpected variation in the absorption of 2-thiothymine and 4-thiothymine, and makes an unanticipated prediction about the nature of the LUMO in 2-selenothymine that is confirmed by quantum chemical calculations. Here, delocalization due to the large size of selenium dominates that due to conjugation; in essence, a 2-center delocalization exerts a greater influence on molecular properties than a 4-center delocalization. The study highlights that the widely used concept of delocalization may be affected not only by the long-established idea of double bond conjugation, but also delocalization owing to the size of atoms.

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2

Sulfur and selenium substituted nucleobases (thymine, cytosine and uracil) are present in tRNA. These substitutions affect a variety of functions such as basepairing selectivity, translation of proteins, and oxygen tolerance in anaerobic microorganisms.1,3-4 Apart from this, thiobases have found wide use in therapeutics in the past few decades. 6-Thioguanine is effective as an anticancer and anti-inflammatory drug5 and 2-thiouracil has been used as an anti-thyroid drug.6 Quite recently, they have been considered as potential photodynamic therapy (PDT) drugs7 and this has led to a number of experimental8-15 and theoretical16-25 studies of these noncanonical nucleobases. PDT is a treatment which involves a drug that is activated by a specific frequency of light to cause cancer cell death, without harming healthy cells.26 Important requirements of a PDT drug are that it has absorption at higher wavelengths (since such radiation penetrates deeper into tissues than shorter wavelength light27), and has a high triplet yield (which leads to the formation of reactive oxygen species 28). In this regard, thiothymines have been suggested as prospective PDT drugs.7, 12 Recently, Pollum et al have performed a comparative study of the absorption spectra and triplet yields of thiothymines.12 As expected, they observed a redshift in the absorption due to sulfur substitution with respect to the parent molecule, thymine (Thy). Unexpectedly however, they observed that thionation at the C4 position

of Thy led to a significantly greater red-shift than thionation at the C2 position (Figure 1 shows atom numbering). This was also observed in uracil by the same authors, which only differs from Thy by the absence of a methyl group at C5.13 This curious observation was explained by Bai and Barbatti who noted that in 2thiothymine (2tThy) and 4-thiothymine (4tThy) the excitation took place to LUMOs with different electron density distributions.22 In 2tThy the electron density of the LUMO extends over the oxygen atom, whereas in 4tThy it extends over sulfur.29 The greater redshift in 4tThy was attributed to the LUMO being along the weaker C=S bond as compared to the C=O bond in 2tThy. This brings up the puzzling question, “Why does the LUMO extend over oxygen or sulfur depending on the site of sulfur substitution?” The answer, besides being of fundamental interest, can help predict the absorption properties of other sulfur and selenium substituted thymine or uracil analogues. Moreover, knowledge of the nature of the LUMO can rationalize certain chemical properties such as electrophilic sites in the molecule.30 In this article, we seek to explain how and why the nature and energy of the LUMO and other frontier orbitals, which are responsible for the observed trends in absorption spectra, vary across sulfur-substituted thymines. Our hypothesis invokes an intriguing interplay of two types of electronic delocalization, which can either compete with or reinforce each other within a molecule. The hypothesis is tested on selenium-substituted

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thymines. A striking prediction is made about the nature of the LUMO in 2-selenothymine (2SeThy), which is validated by electronic structure calculations. Similar results are obtained for tellurium substituted thymines. Our investigation is based on calculating accurate vertical excitation energies, assigning these transitions to molecular orbitals, examining the nature of these orbitals, and using a simple particle-in-a-box (PIB) model to obtain trends in these orbital energies based on their extent of delocalization. To ascertain the effect of cyclic delocalization, which might appear significant in Thy, and which has not been considered in our PIB model, we have studied model aliphatic systems based on Thy where this effect can be scrutinized.

Figure 1. Molecules studied in this work. The orientation of 5 the hydrogen atoms of the methyl group at C corresponds to the calculated most stable conformation.

All calculations of vertical excitation energies were performed at the MS-CASPT231-32 (level shift of 0.3) and EOM-CCSD33 level of theory with the cc-pVTZ34-37 (ccpVTZ-PP38 for Te) basis set. The state-averaged complete active space self-consistent field (SA-CASSCF) reference wave function used for MS-CASPT2 was composed of the lowest six singlet states with the intention of including at least two bright states for all molecules. The active space consists of 14 electrons in 10 orbitals and is explicitly shown for each molecule in Figure S1 of the Supporting Information (SI). Molecular geometries were optimized at the Møller-Plesset second-order perturbation (MP2) level of theory39 with the cc-pVDZ (cc-pVDZ-PP38 for Te) basis set34-37 and frequency calculations were performed to confirm that these were true minima. All calculations were performed using the Molpro 201240-41 suite of quantum chemistry programs and Molden42 was used to visualize molecular orbitals.

3.1. Ground State Structure. The optimized structures of all the molecules studied (Figure 1) were found to have Cs symmetry, although no symmetry constraint was explicitly imposed. Our calculations show that of the three hydrogen atoms of the methyl group at C5, the one that is in the plane of the molecule, points away from the oxygen (or sulfur, selenium) atom at C4 (Figure 1). An earlier suggestion of another minimum energy structure for Thy, where the planar hydrogen atom of the methyl group points towards the oxygen,43 is in fact a first order

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saddle point in light of our frequency calculations. The energy profile along the rotation of the methyl single bond explains the nature of the imaginary frequency mode (Figure S2(a)). The higher barrier in the case of 2,4dithiothymine (dtThy), along with consideration of van der Waals radii (Figure S2(b)), suggests that sterics play a governing role in determining the conformation of the methyl group in the minimum energy geometry. 3.2. Hypothesis for the Nature of the LUMO. The vertical excitation energies and the orbital nature of the excitations of the lowest excited states of Thy at the MSCASPT2 level are presented in Table 1, along with the energies of the corresponding states at the EOM-CCSD level. Calculated oscillator strengths are also provided. There is good agreement in energy values between the two electronic structure methods, and these energies concur with previous theoretical studies.22,43-45 While vertical excitation energies cannot be directly compared to experimentally measured electronic excitation spectra, they are consistent with the measured peak maxima.46 Oscillator strengths are nearly zero for the nπ* states, while they are significant for the ππ* states suggesting that the latter are the optically bright states. The two distinct bands in the longest wavelength region of the absorption spectrum of Thy can be assigned to the first two ππ* states. Likewise, results for the different sulfur and selenium substituted thymines using MS-CASPT2 (Table 2) and EOM-CCSD (Table S1) are presented, and the vertical energies of the optically bright states are found to be consistent with the experimental peak maxima (Table S1). For all molecules, the lowest ππ* state is of primary interest in the current study and is indicated in bold in Tables 1, 2 and S1. The orbitals involved in the two lowest bright states, optimized at the SA-CASSCF level are shown in Figure 2. CASSCF orbitals do not have meaningful energies. Therefore, to analyze their energy trends, they are tallied with the corresponding canonical Hartree-Fock (HF) orbitals which are qualitatively similar and have well defined orbital energies (Figure S1). Table 1. Vertical excitation energies (eV) with oscillator strengths in parenthesesa calculated at the MS-CASPT2 and EOM-CCSD level of theory at the MP2 optimized geometry of Thy State

MSCASPT2

EOMCCSD

MSb CASPT2

1

5.32 (0.00)

5.20 (0.00)

5.00

1

n4π4* πCπ4*

5.82 (0.18)

5.53 (0.22)

5.03

1

n2π2*

6.69 (0.00)

6.63 (0.00)

6.36

1

π4π4*

6.72 (0.16)

6.83 (0.06)

6.06

1

n2π4*

7.50 (0.00)

7.70 (0.00)

a

c

Experiment

4.95 ± 0.08 6.20 ± 0.08

b

The first bright state is in bold. Calculated values from Ref 22 with a different basis set and state-averaging. c Experimental values from Ref 46 correspond to the peak maxima of the electronic excitation spectrum of Thy.

There are a few noteworthy observations one can make by focusing on the nature and energies of orbitals of Thy


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Figure 2. Orbitals characterizing the electronic transitions to the lowest two bright states for all molecules studied, optimized 2 at the SA-CASSCF level at the MP2 optimized geometry. Subscript ‘2’ denotes location of the orbital primarily on the C =X bond, 4 5 6 ‘4’ on the C =X bond (X=O, S, Se) and ‘C’ on the C =C bond.

Table 2. Vertical excitation energies in eV (oscillator strengths in parenthesis)a calculated at the MS-CASPT2 level of theory at the MP2 optimized ground state geometry. Thiothymines

Selenothymines

2tThy

4tThy

dtThy

2SeThy

4SeThy

dSeThy

State

Energy

State

Energy

State

Energy

State

Energy

State

Energy

State

Energy

1

4.26 (0.00)

1

3.20 (0.00)

1

3.18 (0.00)

1

3.74 (0.00)

1

2.69 (0.00)

1

n4π4*

2.69 (0.00)

5.00 (0.00)

1

4.49 (0.40)

1

4.14 (0.00)

1

4.48 (0.50)

1

3.97 (0.44)

1

n2π2*

3.62 (0.00)

5.22 (0.18)

1

5.19 (0.20)

1

4.15 (0.01)

1

4.90 (0.23)

1

4.94 (0.22)

1

πCπ4*

3.62 (0.02)

5.32 (0.58)

1

6.00 (0.00)

1

4.45 (0.00)

1

5.21 (0.00)

1

5.53 (0.00)

1

n2π4*

3.85 (0.00)

5.80 (0.00)

1

6.27 (0.13)

1

4.65 (0.63)

1

5.86 (0.02)

1

5.85 (0.07)

1

π4π4*

3.98 (0.73)

1

n2π2* n4π4*

1

πCπ4*

1 1

πCπ2* n2π4*

n4π4* πCπ4*

π4π4* n4π2* πCπ2*

n4π4* n2π2* πCπ4*

n2π4* π4π4*

n2π2* πCπ2*

πCπ4* n2π4* π2π2*

n4π4* πCπ4*

π4π4* n4π2* ππ*

a

The first bright state is in bold. EOM-CCSD energies and oscillator strengths, and experimental values are given in Table S1

and the three thiothymines. These observations are schematically shown in Figure S3. 1.

In Thy and all the thiothymines, the natures of the LUMO and LUMO+1 are consistently π4* and π2* respectively. Here, π4* (π2*) denotes a π* orbital located along the C4=X (C2=X) bond where X can be O or S.

2.

In Thy and two of the thiothymines (4tThy and dtThy), the two lowest bright states are both characterized by transitions to the LUMO. In 2tThy, on the other hand, the two lowest bright states are characterized by excitations to the LUMO and LUMO+1; both transitions originate from the same occupied orbital.

3.

The energy gap between the π4* and π2* orbitals ( ), shows a remarkable modulation on single sulfur substitution at two different sites: For canonical Thy, is 2.1 eV. In

2tThy, decreases to 0.7 eV; while in 4tThy, it increases to 2.5 eV. Consider point 1. In 2tThy, the π4* orbital, which extends along C4=O, being the LUMO is unanticipated. A C=S bond is longer and weaker than a C=O bond, and the molecular orbitals in C=S are more delocalized than in C=O. The bonding π orbital in C=S is destabilized and antibonding π* orbital stabilized with respect to the stronger C=O bond. Thus the π2/π2* orbitals (which extend along C2=S) would be expected to be the HOMO/LUMO. Moreover, although the observation in point 2 and the trends in in point 3 might seem justifiable based on the stabilization of a C=S π* orbital with respect to a C=O π* orbital, the very different magnitudes of the changes in for 2tThy and 4tThy with respect to Thy points to a more involved phenomenon.


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All the above observations can be explained by hypothesizing an interplay between two types of delocalization: one due the conjugated C4=X and C5=C6 bonds which is intrinsic to the molecular skeleton of the thymine molecule; two, attributable to the greater size of the atom substituted (X) at either the C2 or the C4 position, i.e., larger the atom substituted, greater the delocalization. Clearly, when X is the same, the π and π* orbitals on C4=X are more delocalized than the orbitals on C2=X. The two types of delocalization compete with each other in the LUMO and LUMO+1 of 2tThy where the π4* (on C4=O) is stabilized by conjugation while the π2* (on C2=S) is stabilized by size-driven delocalization. Conjugation dominates due to which π4* is the LUMO, but the LUMO+1 (where there is size-driven delocalization) gets extremely close in energy to the LUMO. In 4tThy, on the other hand, these two effects enhance each other in the LUMO and are absent in the LUMO+1; the π4* (on C4=S) has both conjugation and size-driven delocalization. This leads to a more delocalized LUMO that is drastically lowered in energy than the LUMO+1 (on C2=O). In dtThy, the two effects neither compete nor enhance each other. The value (1.1 eV) is thus intermediate to that of 2tThy and 4tThy. The is lower than that of Thy because the presence of two weaker C=S (compared to C=O) bonds causes an overall lowering and clustering of states, and consequently a reduction in the gap. 3.3. PIB Model and Prediction for 2SeThy. We have used the PIB model to analyze the implications of our hypothesis. The model is used to estimate energy trends of the LUMO and LUMO+1 energies of Thy and substituted thymines. The PIB model is routinely used for the calculation of HOMO-LUMO energies in π conjugated systems. As described in introductory quantum chemistry textbooks,47-49 the electrons are considered to be independent particles in a onedimensional box whose length is estimated using the constituent bond lengths and an additional distance at the ends of the molecule. In this study, we have employed the PIB model in a different manner to compare the two types of delocalizations within the thymine molecule. Considering our hypothesis, we divide the thymine skeleton into two separate π systems: the 4-electron C6=C5—C4=X system and the 2-electron C2=X system (Figure 3). The various substituted thymines correspond to different combinations of the two π systems where X=O, S, Se. The calculation of the length of the box for each case is shown in Figure S4. Two electrons are filled in each energy state or spatial orbital following the Pauli principle (Figure 3) and the energies of the HOMO and LUMO for each molecule are shown in Table S2 and graphed in Figure S5. The energies of the HOMO are similar for the C6=C5—C4=X and C2=X systems, which is related to the energy of a state being directly proportional to the square of the quantum number (nHOMO=2 for the former and 1 for the latter) and inversely to the square of the box length (the former length is approximately two times the latter, see Figure S4). Furthermore, for different X in either C6=C5—C4=X or C2=X, the HOMO energies do

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Figure 3. Thymine skeleton showing the two types of delocalization modeled by the particle-in-a-box. not change significantly as compared to the LUMO energies (Figure S5). This is because the energy depends on the square of the quantum number and nLUMO is greater than nHOMO. We therefore focus on the energies of the LUMOs to explain the observations about Thy and substituted thymines (Figure 4). The sharper decrease in the energy of the LUMOs of the C2=X system in comparison to the C6=C5—C4=X system stands out in Figure 4. This can be understood by considering the energy expressions for the LUMOs of the C2=X (eq 1) and C6=C5—C4=X (eq 2) systems.

C=X

O C=X

C=C C=X O C=C C=X

where, c is a constant. When X=O,

,

-

-

implying that (Figure 4). On the other hand, for large size of atom X, the C=X length is large, -

and consequently

-

. Since

-

crosses over at large X, the former must fall faster than the latter as the size of X increases. The different redshifts and unusual modulation of for singly substituted thymines can be understood based on the overall trend in the LUMO energies. For example, 2tThy has the components C6=C5—C4=O and C2=S. As seen from Figure 4, the energy of the LUMO of C2=S decreases significantly compared to that of C2=O, but still remains higher than the LUMO of C6=C5—C4=O. This suggests that the LUMO of 2tThy extends over C6=C5— C4=O and the LUMO+1 over C2=S. Notably, the in 2tThy (red pair of arrows near S) becomes much smaller compared to Thy (green double-headed arrow near O) because of the stabilization of the LUMO+1. In 4tThy, the LUMO corresponds to the LUMO of C6=C5—C4=S and (brown double-headed arrow near S) is greater than Thy (green double-headed arrow near O). The different magnitudes of the changes in for 2tThy and 4tThy with respect to Thy are now clearly evident, and originate in the effect of sulfur substitution being different in C2=X versus C6=C5—C4=X. In dtThy, since both the


4

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The Journal of Physical Chemistry observation of the LUMO in these molecules being located on different atoms.22 However, the reason for the LUMOs being this way, a question that is stated in the introduction, had not been investigated so far and can be precisely understood based on the hypothesis presented above.

Figure 4. LUMO energies (in eV) as calculated from the PIB model for the two π systems for X = O, S, Se and Te. The values of estimated from the model are represented by green double-headed arrows for di-substituted, brown double-headed arrows for 4-substituted and red doubleheaded arrows for 2-substituted thymines. The grey dashed lines are the LUMO energies for X=O for the two systems.

3.4. Role of Cyclic Delocalization and Limitations of the Hypothesis. Thy and its sulfur and selenium substituted analogues have certain resonance structures which exhibit cyclic delocalization (Figure S6). To study the influence of this type of cyclic delocalization on our hypothesis which is based on electron delocalization in two distinct π systems in the molecule, we have examined the molecular orbitals of an aliphatic model system obtained by breaking the C4-N3 bond of Thy, whereby the effect of cyclic delocalization is eliminated (Figure 5(a)). We see that in the model molecule, like in Thy, the π* orbital

C6=C5—C4=S and C2=S systems are stabilized by thionation, (green double-headed arrow near S) is lower than in Thy (green double-headed arrow near O), and also intermediate of 4tThy and 2tThy. For the selenothymine series, the model makes an unanticipated prediction. The LUMO energy of the C2=Se system is lower than that of the C6=C5—C4=O system (Figure 4), which suggests that the LUMO in 2SeThy extends over C2=Se in contrast to all the other substituted thymines considered. This prediction is confirmed by ab initio calculations (Figure 2, top two rows) which indicate the flipping of the nature of the LUMO and LUMO+1 in the case of 2SeThy in contrast to the other six molecules. The magnitude of accompanying the crossover of orbital nature is predicted to be small (red pair of arrows near Se in Figure 4), and in line with this, the for 2SeThy is eV (Figure S1). The negative sign indicates that the π2* (along C2=Se) has flipped to be lower in energy than the π4* (along C6=C5—C4=O). A similar observation is made for tellurium substituted thymines (2TeThy and 4TeThy). The orbitals of 2TeThy and 4TeThy, are in fact strikingly similar to the orbitals of 2SeThy and 4SeThy respectively (Figure S1). The LUMO energies calculated from the PIB model not only explain the modulation of , but also successfully predict the origin of redshifts in the absorption spectra of these molecules. The underlying premise is that in the sulfur substituted thymines, the energies of the LUMOs are most significant in determining redshifts.22 From Figure 4, we see the “lowest energy O” is predicted to extend over C6=C5—C4=O for Thy and 2tThy, and on C6=C5—C4=S for 4tThy and dtThy. Incidentally, this persistent delocalization of the LUMO on the 4th position means that it is located on different atoms (O or S) depending on the site of substitution (2tThy or 4tThy respectively). In previous work, the explanation of the different redshifts in 2tThy or 4tThy was based on the

Figure 5. Aliphatic models constructed by breaking Thy between bonds (a) N3-C4 (red line), and (b) C4-C5 (blue line) respectively to examine the role of cyclic delocalization.

located on the 4th position continues to be the LUMO and is delocalized over C6=C5—C4=O, while the π* orbital located on the 2nd position is higher in energy and extends primarily over C2=O (Figure S7(a)). Thus, cyclic delocalization does not qualitatively affect the nature of the LUMO. However, if we consider another aliphatic model system obtained by breaking the C4-C5 bond of Thy (Figure 5(b)), where in addition to cyclic delocalization, conjugate delocalization is absent, we see the orbitals are significantly different from Thy (Figure S7(b)). Now the two lowest π* orbitals are equally delocalized over both C=O bonds. Based on the two model systems, it is evident that the conjugated C6=C5—C4=O unit plays a governing role in determining the nature of the LUMO of Thy, and cyclic delocalization is insignificant. A limitation of our hypothesis is the underlying assumption that the 4-electron and 2-electron π systems in Thy do not interact at all. Because of this assumption, certain observations cannot be accounted for. For instance, the LUMO energy predicted from Figure 4 for 2tThy is the same as that of Thy, which incorrectly implies that substitution at C2 does not result in a redshift. Explaining this redshift would require taking into account an interaction between the two π systems. In that case, the presence of a C=S bond in the molecule, which is weaker than the C=O bond, will affect the C=CC=O system and can be expected to lower the energy of all the states as compared to Thy. A reflection of this is the lowered energy of all the calculated excited states of


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2tThy with respect to Thy (Tables 1 and 2). In our study, however, the approach is kept deliberately simple by considering only the most influential factors, thereby allowing us to analyze the effect of substitution and obtain valuable physical insight. 3.5. Effect on Electrophilicity. The interplay between the two types of electronic delocalization has implications on the chemical properties of thymines as well. For instance, the LUMO of Thy (Figure 2 and Figure S1) is delocalized along the C6-C5-C4=O region and the largest coefficient of the LUMO is on C6 followed by C4 and none at all on C2. This suggests that nucleophilic addition is most likely to happen on C6 rather than on the carbonyl carbons C4 and C2,30 and this is confirmed by experiments.30, 50-52 For instance, when thymidine reacts with N-bromosuccinamide and sodium azide, addition of the nucleophile (azide) takes place on C6.52 This trend can be expected to persist in the sulfur substituted thymines based on the strong similarity of their LUMOs with that of Thy (Figure 2 and Figure S1). Interestingly, in 4tThy, where conjugation and size-driven delocalization assist each other, the LUMO energy is significantly lowered as compared to Thy and thus 4tThy can be expected to be a stronger electrophile as compared to Thy. In 2tThy however, the LUMO energy does not change appreciably as compared to Thy but decreases dramatically, which suggests a possible competing electrophilic site, namely the C2 carbonyl carbon atom. In 2SeThy, based on the crossover of the LUMO to the C2-O region (Figure 2 and Figure S1), nucleophilic addition is predicted to take place at C2 in this molecule. Additionally, considerations such as the hard-soft classification of electrophiles (which are affected by van der Waals radius and electronegativity among other aspects), and the groups next to the carbonyl group (for instance electron donating/withdrawing propensity) play a role. These factors may influence the site of nucleophilic attack and need to be kept in mind while predicting the site of nucleophilic addition.

A hypothesis providing a fundamental basis for explaining the unexpected trends in absorption spectra, and chemical properties like electrophilicity of different substituted thymine nucleobases is proposed. The different redshifts in the two singly-substituted sulfur thymines as compared to Thy are explained by considering an interplay between two types of delocalization: One, due to the conjugation of the C4=X (X=O, S) bond with the C5=C6 bond which is intrinsic to the thymine skeleton. Two, due to the longer C=S bond compared to the C=O bond which is because of the nature of substitution. While these factors compete with each other in 2tThy (with the first factor dominating), they augment each other in 4tThy. In both molecules, the LUMO is predicted to be located along the C4=X bond, which happens to be along a C=O bond in 2tThy, while along a C=S bond in 4tThy. The implications of the hypothesis are analyzed using a PIB model with variable lengths and electron

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occupations. The model explains the characteristic nature of the LUMO, as well as the unusual modulation in the energy gap between LUMO and LUMO+1 orbitals on sulfur substitution in Thy. Moreover, the model predicts an intriguing crossover in the nature of the LUMO in 2SeThy and 2TeThy where the size of the substituted atom, selenium/tellurium, is even larger than sulfur. In effect, a 2-center delocalization (C=Se/Te) can surpass a 4-center delocalization (C=C—C=O) in its influence on molecular properties. This is verified using ab initio quantum chemical calculations. The PIB model can be applied to any molecule, where there are two or more distinct π systems, to predict the location of the LUMO. However, given the qualitative nature of the predictions, it is likely to be most useful for obtaining trends when there is a systematic change in size of one of the π systems while the others remain unchanged. In general, this work provides a new framework to understand the variation in physical and chemical properties of molecules, obtained from atomic substitutions at different sites of a single parent molecule. It emphasizes the importance of atomic size, in addition to double-bond conjugation, in determining electronic delocalization in molecules.

Supporting Information. SA-CASSCF and HF orbitals, energy profile along methyl rotation, nature of lowest energy excitations and modulation of LUMO and LUMO+1 gap, box lengths used in the PIB model calculations, plot of HOMO and LUMO energies from the PIB model, resonance structures of thymine, SA-CASSCF orbitals of aliphatic models, Table with EOM-CCSD and MS-CASPT2 energies and oscillator strengths and experimental energies, Table with HOMO and LUMO energies calculated from the PIB model, and Cartesian coordinates of all optimized structures. This material is available free of charge via the Internet at http://pubs.acs.org.

*E-mail: [email protected] (M.A.M.) *E-mail: [email protected] (A.H.) The authors declare no competing financial interest.

We are grateful to Dr. Amrita B. Hazra and Dr. Arnab Mukherjee, both from IISER Pune for valuable suggestions. For financial support we acknowledge the Science and Engineering Research Board, Government of India (Project No. GAP/DST-SERB/CHE-12-0086). We also acknowledge CDAC Pune for computing facilities. M.A.M. thanks IISER Pune for a research fellowship.

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TOC Graphic


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Interplay between Conjugation and Size-Driven Delocalization Leads

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