Role of Explicit Solvation in the Simulation of Resonance Raman

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B: Liquids, Chemical and Dynamical Processes in Solution, Spectroscopy in Solution

Role of Explicit Solvation in the Simulation of Resonance Raman Spectra within Short-Time Dynamics Approximation Sayan Mondal, and Chandrabhas Narayana J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.9b07471 • Publication Date (Web): 13 Aug 2019 Downloaded from pubs.acs.org on August 13, 2019

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The Journal of Physical Chemistry

Role of Explicit Solvation in the Simulation of Resonance Raman Spectra within Short-time Dynamics Approximation Sayan Mondal a,b*, and Chandrabhas Narayana a,c* Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore ‐ 560064, Karnataka, India

aChemistry

and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore ‐ 560064, Karnataka, India bCurrent

Address: Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot ‐ 76100, Israel cSchool

of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore ‐ 560064, Karnataka, India *Corresponding Author: Sayan Mondal, Chandrabhas Narayana Email: [email protected]; [email protected] Reprint Author: Sayan Mondal, [email protected]

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Abstract In short-time dynamics approximation (STA) formalism relative Resonance Raman (RR) intensity of a vibrational mode primarily depends on magnitude of square of the excited state gradient along the corresponding normal coordinate, ground state normal mode eigenvector and harmonic vibrational wavenumbers. In this study, through simulation of RR spectra of guanosine-5′monophosphate (GMP) in two ππ* singlet excited states; we analyze how the explicitly hydrogenbonded local solvation structure of the chromophore dictate intensities of the RR active modes in unprecedented manner. We show that the accuracy of the structural model of solvated chromophore plays a decisive role in determining an optimal theoretical method for prediction of the Frank-Condon region of the ππ* excited states. 9-methylguanine (9-meG) in complex with six water molecules (9‐meG•6H2O) is found out to be the most accurate one for describing GMP in two different bright electronic states. We find that explicit hydrogen-bonded water molecules strongly influence computed RR intensities of GMP by modulating both the ground state normal mode vectors, and the excited state energy gradients. We find that simultaneous inclusion of six explicit waters to describe the solute-solvent interaction near all hydration sites is essential for reliable prediction of the features of RR spectra in Lb and Bb electronic states of GMP.


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Introduction Vibrational resonance Raman (RR) scattering is a key spectroscopic tool to probe molecular structure in ground and electronic excited states with great sensitivity and selectivity. The sensitivity in RR spectroscopy arises from enhancement of signal up to 104-106 over normal Raman scattering as the Raman excitation wavelength in tuned to fall within one of the electronic transitions of the molecule.1,2 Selectivity in RR spectroscopy in attained by resonance enhancement of a specific set of vibrational modes by tuning the excitation laser to different excited state of the molecule. The intensity enhancement of a normal mode depends on vibronic polarizability that encodes information of the resonant electronic state. Thus, RR spectrum contains two types of information; the band positions report on vibrational transitions that directly relate to ground state geometry and the band intensity carries information of the vibronic potential energy surface (PES) of the resonant excited state of the molecule. Because of high molecular specificity and selective enhancement through tuning of excitation wavelengths, RR spectroscopy became a sensitive and useful tool for investigating excited states of light absorbing natural chromophores such as nucleobases that form DNA and RNA,3,4 and aromatic amino acids that are building blocks of proteins.5,6 RR, being a second-order process is described by the Kramers-Hisenberg-Dirac (KHD) dispersion relation.7,8 There are three fundamental formalisms that can be employed to compute intensity of RR active modes of a molecule: Firstly, time-independent (TI) approach or vibronic theory where sum-over all intermediate vibronic states are taken into account, developed by Shorygin1,9 and later by Albrecht and coworkers.10,11 Secondly, Kramers-Kronig (KK) transformation that relates optical absorption spectra with molecular polarizability of a molecule,12,13 and has been employed to compute RR spectrum for small molecules.14–16 Thirdly, the time-dependent (TD) picture of RR process, developed by Lee and Heller17 through mathematical transformation of the timeindependent KHD equation into an integral in time domain.18 In this approach, RR polarizability is computed by propagating a wavepacket of the initial state over the potential energy surface (PES) of electronic excited state, and is known as time-dependent wave-packet propagation (TDWP) approach. For medium sized molecules with many vibrational modes, the computation of the sums over the intermediate vibrational states quickly become computationally very demanding in TI approach, and is often bypassed by using TD formalism.19 More recently 3 ACS Paragon Plus Environment


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development of a new methodology to compute RR spectra based on using delocalized internal coordinates within harmonic TD framework is also reported suited for flexible molecular systems.20 In general, a number of approximations are employed to reduce the computation bottleneck of evaluating equilibrium geometries in multiple electronic states, and the associated PES, their transition dipole moment (µ), and nuclear coordinate dependence of µ, to simplify computation of RR spectrum. Being a scattering phenomenon, RR process completes within tens of femtoseconds (fs) following photoexcitation, and thus RR process is often described within short-time approximation (STA).21,22 In this approach, Herzberg-Teller (HT) vibronic coupling and Duschinsky mixing is neglected, and identical harmonic PES with only shifted minima is assumed for both ground and excited states; is commonly known as the independent mode, displaced harmonic oscillator (IMDHO) model. When only short-time dynamics is taken into account, relative RR intensities can be evaluated from ground state vibrational frequencies, normal coordinate vectors, and the gradients of the FC excited PES along each vibrational coordinate at equilibrium geometry without explicit knowledge of vibrational wavefunctions of the resonant state. Within IMDHO and STA approximation RR intensities are directly proportional to the slope of the excited electronic PES along normal coordinates. Apart from being computationally inexpensive, STA presents an attractive methodology within which performance of theoretical methods for computation of different ground and excited state properties can be analyzed.23–28 Since its introduction,29 and application for computation of molecular valence excited states30,31, timedependent density functional theory (TD‐DFT) has become a standard technique for investigating excited state properties.32,33 STA approach in conjunction with TD‐DFT evaluated excited state gradients has been very useful to interpret solution state RR spectra of several molecular systems.24,34–42 A central aspect in modelling spectroscopic properties of molecules in solution is the correct description of the solvation, for the computation of ground and excited state properties. Solvent effect is traditionally incorporated with implicit solvation, for example, polarizable continuum model (PCM) to account for bulk dielectric behavior of water.43–45 Electrostatic and directional non-covalent interactions also play important role in solution state. Necessity of including such interactions has been documented in several reports where explicit water molecules 4 ACS Paragon Plus Environment

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within first solvation shell were incorporated for accurate prediction of different molecular properties,46–52 and photodynamics on electronic excited state surfaces.53,54 However, in case of prediction of RR intensity, such analyses is not well documented for small to medium sized molecular system. Computation of RR intensities within STA provides with a framework to analyze role of such solvent molecule on four key molecular properties; electronic transitions, vibrational frequencies, ground state normal modes, and ES energy gradients. To this end, we take guanosine-5′-monophosphate (GMP), the nucleotide of guanine (Gua) as a model system to understand role of explicit solvents in first solvation shell on predicted RR intensities. RR spectroscopy has been extensively employed to nucleic acid bases, and few reports are published on simulation of their RR spectra also.34,35,55–58 Our choice of this chromophore is mainly because of the fact that Gua is one of the most studied purine systems using RR spectroscopy, and a rich database of RR spectrum in different electronic states are well documented.3,59–61 Use of explicit solvation has been previously reported to model energetics of La and Lb excited states of GMP correctly.50,62 Explicit treatment of water molecules become more important where the chromophore like Gua has hydrogen-bonding (H-bonding) sites, such as carbonyl and amino moiety. Schlegel and coworkers have reported a significant improvement in prediction of pKa by including explicit water molecules near the site of protonation of Gua.52 We expect these explicit H-bonds can affect properties of both ground and electronic excited states in non-trivial manner. In this contribution, we deduce role of such explicit solute-solvent interaction on predicted RR intensities of GMP in Lb and Bb electronic states. Analysis of RR excitation profiles (REP) have shown that the instantaneous nuclear dynamics (within in few tens of fs after photoexcitation) on these excited states of Gua, and in similar sized nucleobase systems are described well within Frank-Condon approximation, neglecting HT effects and Duschinsky mixing. This is a manifestation of the fact that the geometric distortions in Gua in Lb and Bb excited states compared to ground state structure are mostly planar, leading to resonant enhancement through Albrecht’s A term.10,11 Thus, the application of STA approximation is expected to capture the essential feature of RR spectra of Gua in these electronic states.



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Comparative analysis of RR spectra on two different bright electronic states enable us to deduce how normal modes of Gua are driven by electronic excitation within FC region of excited PES, and produce enhancement of specific vibrational modes through FC coupling. We have used four different structural models; viz., isolated N9H‐Gua and 9-methylguanine (9-meG), N9H‐Gua with seven waters (N9H‐Gua•7H2O), and 9˗meG with six water (9‐meG•6H2O) molecules, (Figure 1) and establish in a step-by-step manner the absolute necessity to include the explicit waters to describe solvated GMP properly. The manuscript is arranged in the following manner. In the method section, we describe, the necessary theory of computing RR intensities within STA approximation, and the computation of all the ground and excited state properties. In the result section, we first describe the (a) ground state structure, (b) vertical transition engines of nature of the singlet excited states, (c) vibrational normal modes of GMP. Next, we show the exclusive role that each strategically placed water molecules play in producing correct RR intensities, and thus can describe the short-time dynamics of GMP. In the following two section, we analyze RR spectra of GMP in Lb (~ 248 nm), and Bb (~ 210 nm) states in comparison with the experimental ones. We find that explicit solvation surrounding GMP modulates the ground state vibrational normal modes more drastically than the gradients on electronic excited states, and affects the RR spectrum in unprecedented manner. Theoretical and computational methods Theory of Resonance Raman scattering within short-time approximation (STA) Within STA approach of calculating RR intensity the assumptions are, (i) Potential energy surfaces of ground and excited states are harmonic in nature, and are only shifted along RR active normal modes; (ii) no change of vibrational frequency occurs in excited state compared to those in ground state; and (iii) mode mixing among normal modes of excited and ground state (also known as the Duschinsky rotation63) is neglected. This formalism is also known as independent mode displaced harmonic oscillator (IMDHO) model.64 The intensity (Ik) of a resonant fundamental (ωk) within STA is expressed as,42,65 ∂𝐸𝑒 𝐼𝑘 ∝ 𝑔 𝑔 𝜔𝑘 𝜇𝑘 ∂𝑄𝑘 1

2

( )

(1)

𝐹𝐶


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where ∂Ee/∂Qk is the gradient on eth electronic excited state surface along kth normal mode in mass weighted normal coordinate and ωk and μk being frequency and reduced mass of kth vibrational mode in ground electronic state. The superscript g and e stand for ground and electronic excited state respectively. ‘FC’ indicates that excited state gradients are evaluated at ground state equilibrium geometry, being the case of FC excitation. Excited state gradient, ∂Ee/∂Qk is computed by projecting non-mass weighted cartesian gradients, computed on the relevant electronic state evaluated at FC geometry on mass-weighted normal mode coordinates computed on ground state equilibrium geometry,25 ∂𝐸𝑒 ∂𝑄𝑘

( )

𝐹𝐶

= 𝐿𝑇

∂𝐸𝑒 ∂𝑥

( )

(2)

𝐹𝐶

where the L is the orthogonal matrix obtained as solution of ground state normal mode eigenvalue problem. Transpose of L i.e. LT performs the basis change from cartesian coordinate to normal mode coordinate. For a molecule having N atoms both (∂Ee/∂Qk) and (∂Ee/∂x) are column vector of (3N‒6) x 1 and 3N x 1 dimension respectively and L is of 3N x (3N‒6) dimension. The cartesian gradients are computed from analytical derivative of the excited state electronic energy along nonmass weighted cartesian coordinate. The orthogonal matrix, L that describes ground state normal modes of a molecule, and reduced mass of each vibrational modes are computed using B3LYP functional. All the quantities described here are extracted from output of Gaussian program using locally written Python script, and RR intensity was computed with Eq 1. Computational details All quantum chemical computations are performed with Gaussian 09 program suit.66 Ground states (S0) of isolated N9H‐Gua, N9H‐Gua•7H2O and 9‐meG•6H2O were optimized using B3LYP exchange˗correlation functional along with 6‒311+G(2d,p) atom centered Gaussian basis set without any symmetry constraints. (Table S1-S6 in supporting information describe ground state equilibrium geometries of all models) A minimum on S0 surface is ensured as stationary point by harmonic vibrational analysis. Cluster˗continuum method is a hybrid solvation approach where implicit solvation such as polarizable continuum model or PCM is used in conjunction with introduction of explicit water molecules within first solvation shell to capture effect of hydrogen bonding interactions.48 We place six water molecules strategically around 9‐meG so that directional hydrogen bonds are formed between water molecules and polar sites of purine ring; O6, 7 ACS Paragon Plus Environment


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H1, N3 and N7 sites in 9-meG•6H2O complex. To deduce the effect of bulky ribophosphate group at N9 position of purine ring on simulated absorption and RR spectra, N9‒H neutral form of Gua is also modeled (N9H-Gua•7H2O) vis-à-vis 9-meG system. In case of N9H‒Gua an additional water molecule was necessary to form an extra hydrogen bond at N9H site. The UV‐Vis absorption spectra were computed as vertical excitation energies at TD˗B3LYP level using non-equilibrium PCM solvation at FC geometry with the same basis set that was used for S0 optimization. Oscillator strengths are converted to extinction coefficients and stick spectra are deconvoluted with Gaussian functions of fixed full width of 3500 cm‐1 to simulate absorption lineshape. Vibrational frequencies and molecular orbitals are visualized using Chemcraft 1.6.67 Potential energy distribution (PED) analysis was performed with VEDA v4.0.68 Results and discussions A. Ground state Structure and vibrational normal modes of GMP Structure in electronic ground state of both N9H-Gua and 9-meG ,and their complex with water molecules were found to be planar except the amino moiety which is pyramidal as also reported in earlier studies for Gua and other nucleobases.69,70 We find that presence of explicit water molecules that make two H-bonds with hydrogen atoms of amino moiety reduce pyramidalization at N2 site, compared to those in isolated base. (Table S7 in Supporting Information) Largest change in structural parameters because of formation of hydrogen bonds with waters is seen in reduction of C6=O6 and C2–N2 bond lengths by 0.015 Å and 0.02 Å respectively (Table S8 of Supporting information). These changes result in downshift of vibrational frequencies of associated stretching modes on par with experimental observations. (see “Vibrational Wavenumbers and Ground State Normal Modes” section) Other than C6=O bond, all other bond lengths connecting heavy atoms of purine ring are in good agreement with X-ray crystallographic structural paramers.71,72 (Table S8 of Supporting information) Vibrational spectra of Gua and its different N9 substituted species have been investigated experimentally in polycrystalline47,73, solution3,60,61,73–76 and adsorbed state47,77. Normal modes of Gua have been previously described most comprehensively by Giese and McNaughton, by using explicit solvation model to account for hydration effect on computed harmonic frequencies in normal Raman spectra (NRS) of polycrystalline guanine.47 Jayanth et al. have established N1H‐Keto as the prevalent tautomer of GMP at neutral pH using RR spectroscopy, and DFT 8 ACS Paragon Plus Environment

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computation on the isolated N9H-Gua.61 In the current report, we explore effect of solvation on not only wavenumbers, but also on composition of normal modes in explicit water complexed model vis-à-vis isolated base. Computed vibrational wavenumbers on different models of GMP using B3LYP functional and basis sets are described in Table S9 of supporting information along with experimentally observed wavenumbers, and the computed PEDs are described in Table S11 of supporting information. Wavenumber of carbonyl stretching (C=O) frequency is normally over estimated by DFT, and is predicted at more than ~100 cm˗1 higher wavenumber than experimentally observed value (~ 1689 cm˗1) with the use of B3LYP functional.47,61 We find that, inclusion of implicit solvation via continuum reaction field (PCM) alone improves computed harmonic wavenumber of this mode and predicts at 1697 cm˗1, in excellent agreement with experimental value. However, in 9‐meG•6H2O complex, C=O stretching mode is further downshifted to 1665 cm-1. This downshift is attributed to double hydrogen bond accepting character of O6 atom with two surrounding water molecules and thus weakening of polar C=O bond. Explicit H-bonding interactions affect another exocyclic mode, the NH2 scissoring vibration at 1607 cm-1. Frequency of this mode is predicted ~ 1640 cm-1 in isolated N9H‐Gua and 9‐meG, but upshifts to ~ 1700 cm-1 in water surrounded complex. This is encountered by Giese et al. in case of vibrational analysis of guanine heptahydrate in vacuo.47 In complex with water molecules, in-plane bending of N1H moiety is found to be mixed with NH2 scissoring mode in minor amount. The non-trivial reason behind the upshift is found to be a simultaneous decrease (3%) in reduced mass and increase (4%) of force constant of this mode in 9‐meG•6H2O, compared to those in isolated 9‐meG. Potential energy distributions (PED) associated with key vibrational modes undergo major reorganization in presence of explicit water molecules. Example of such mode reorganization in three normal modes of GMP is depicted in Figure 2. C=O stretching mode whose frequency is very sensitive to solvent environment undergoes changes in PED as well. Relative contribution of C=O coordinate decreases with introduction of increasing number of water molecules making Hbonds with carbonyl oxygen. (Figure 2, a-d) In a ring stretching vibration, methyl at N9 (in 9-meG models) causes either complete decoupling or decrease of contribution from internal coordinates localized on both the rings. (Figure 2, e-h) We analyze how are these reorganizations in normal modes manifested in computed RR intensities in the next section. 9 ACS Paragon Plus Environment


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Introduction of methyl group at N9 position in place of ribophosphate moiety also has distinct effect on both the computed vibrational wavenumbers, and RR intensities. The vibrational modes that undergo change in wavenumber are primarily localized on the imidazole ring of purine. In experimental Raman spectrum, a ring breathing mode comprising imidazole in-plane deformation occurring at 935 cm˗1 in guanine47, upshifts to 1020 cm˗1 in GMP.61 This mode is predicted at 962 cm-1 when computed on N9H‐Gua•7H2O complex. However, introduction of CH3 at N9 position (in 9-meG•6H2O) shifts this band to 1035 cm˗1 which is closer to the experimental value, observed in GMP RR spectrum. (Table S 9 of supporting information) We find that bulky methyl group decouples from in-plane ring deformation, and thus decreases reduced mass of this mode and causes the upshift. B. Character of ππ* excitations, and Excited State Energy Gradients of GMP TD-DFT computed valance excited states of Gua chromophore computed on 9-meGua•6H2O are summarized in Table 1. The molecular orbitals that are associated with each electronic transitions are depicted in Figure 3. Transition dipole moments of Lb and Bb states are oriented along the long molecular axis (Figure 1, a) of the purine base, while La state is polarized nearly along short axis of the purine ring of Gua,78 in agreement with previously reported experimental results.7980818278 Excited state electronic structure of Gua, especially the keto N9H and keto N7H forms have been previously carried out at different levels of theory including both wave-function-based methods,83,8485,868788, and DFT based approaches.48,51,62,89–93 Most of these studies other than a few85,90,91 have focused on computation of vertical excitation energies of La and Lb states that lie within 260 nm absorption band of GMP. Pure ππ* character of these two states is evident from visual inspection of involved molecular orbitals (Figure 3a and 3b). Other than La and Lb states that are extensively studied due to their role in photo-stability of GMP upon UV 260 nm excitation, there are strongly polarized ππ* states in UV-C region at ~ 210 nm. One such electronic state, Bb has been detected in polarized reflection experiments on 9ethylguanine (9-etG) at 205.7 nm and at 204 nm in aqueous solution and crystalline state respectively.81 Bb state is characterized by high oscillator strength of 0.4, and is of ππ* character (Figure 3c). Computed transition energy of Bb state for 9‐meG•6H2O complex is 5.97 eV which is in close agreement with experimental value (6.21 ± 0.07 eV) and lies within typical error94 of TD‐DFT method. This state for N9H‐Gua•7H2O complex at 6.26 eV is in fact in better agreement 10 ACS Paragon Plus Environment

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with average experimental value (6.21 eV or 200 nm) Gua. (Table 1) Computed oscillator strength of 0.35 for 9‐meG model is close to CASSCF/CASPT2 computed value of 0.29.85 The responsible configuration for Bb state is found to be primarily H‒1→L (88 %), in agreement with previously reported singly excited configuration; H‒1→L (51%) computed at CASSCF/CASPT2 level on N9H-Gua.85 Similar nature of Lb and Bb state are obtained on application of TD-DFT with other functionals also. (Table S10 in Supporting Information) Effect of explicit hydrogen bonding at amino, O6 and N7 site with water molecules is seen through a major improvement of ~ 0.3 eV in predicted vertical electronic excitation energy when seven explicit H2O molecules were introduced around isolated N9H‐Gua. On the blue side of Bb state, another ππ* transition (will be referred as S11 here after) of lies at 6.63 ± 0.05 eV (~ 187 nm) of energy and is characterized by an oscillator strength of 0.5 in solution state (Table 1).81 TD‐DFT predicts this state to be located at 6.39 eV and 6.28 eV for N9H‐Gua•7H2O and 9‐meG•6H2O complex respectively; in good agreement (within 0.2 eV) with previous ab initio results computed at CASSCF/CASPT2,85 and TD‐DFT methods.91 (Table 1) Though computed oscillator strength of 0.16 is less than experimentally determined and previously computed value85, the TD-B3LYP computed state configuration of H–3→L (91 %) correctly describes a pure ππ* character of this transition (Figure 3c). Overall, we observe that in addition to use of gaussian basis sets augmented with diffuse functions, consideration of explicit water molecules significantly improves computed transition energy and state configurations (MO description) in case of high energy Bb state. Computed transition energy for 1ππ* state (La) on 9‐meG•6H2O complex, 4.49 eV agrees reasonably well with average experimental value (4.47 eV) than the same calculated (at 4.79 eV) for isolated N9H‐Gua model. Electrostatic interactions of explicit solvent molecules have sensitive effect on transition energies of ππ* singlet states, also previously reported Zhao et al. for similar molecules.48 An assessment of accuracy in predicted vertical transition energies of four ππ* states of GMP, computed on three different models is depicted in Figure S1 of supporting information. Though excitation energies for Bb and higher energy states are underestimated from experimental values by 0.25 eV, overall accuracy for computed energies of four ππ* states on 9˗meG•6H2O model (standard deviation = 0.03 eV) is higher than other two models. In the preceding section, 11 ACS Paragon Plus Environment


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we have seen that vibrational frequencies are much more sensitive than the vertical transition energies to subtle structural changes of the chromophore because of change in solvation structure. We would like to note that assessment of a theoretical method and physical molecular models from comparison of vertical excitation energies with experientially measured transitions can be misleading at times, because we do not explicitly take into account vibronic coupling. Physically, electronic transition is not vertical and the difference between vertical and 0‒0 transition can be significant.95 Thus, role of the explicit waters molecules are analyzed more rigorously in prediction of more sensitive parameters such as, vibrational wavenumbers and RR intensities states in subsequent sections. Direction and magnitude of excited state energy gradients which are the last ingredients in computation of RR intensities, are strongly dependent on the solvation structure of the chromophore itself. Directions of cartesian forces on each atoms of purine ring, computed on four different models, and with four different functionals are shown in Figure 4 in Lb electronic state. It is observed that forces on O6, N2, C2, N1, C8 and H8 atoms are affected due to either the chosen model system or choice of functional. In general, introduction of methyl affects force on C8 and H8 atoms, and choice of functional primarily modulates those on N2, N1 and O6 atoms. Moreover, explicit hydrogen bonded water molecules also have major impact on altering directions of forces exerted on N1, N2, O6 and N9 atoms. It is important to note that, while change of forces on hydrogen bonding sites such as N1, N2, O6 and N7 are expected in 9-meG•6H2O model compared to those in isolated 9-meG, significant modulation of force on N9 is non-trivial. However, we also find that direction of forces on N7 atom does not change in any explicitly solvated model. In succeeding section, we discuss how do this interplay of modulation in normal mode vectors and direction of excited state energy gradients ultimately affect the computed RR intensities. The manifestation of these two effects on evaluation of excited state gradients is much more profound in case of Bb electronic state (Figure S2 in Supporting Information), and will be discussed later. C. Role of explicit solvent molecules on computed RR intensities of GMP Impact of implicit solvation on RR spectrum of medium sized molecules are reported earlier.34,35 A molecular system differing in explicit solvation structures is expected to reflect modulation of normal mode compositions, specifically in the modes that involve the atoms making explicit Hbonds with immediate local environment. (Figure 2) The changes in amplitude and direction of 12 ACS Paragon Plus Environment

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ground state normal modes are expected to affect the projected excited state energy gradient, and thus the computed RR spectrum according to equation 2. To elucidate impact of explicit solvation on GS normal mode vectors, RR spectrum of isolated 9-meG in Bb state have been computed in a hybrid fashion. Excited state gradients are computed with TD-B3LYP/6-311+G(2d,p)//PCM level, while ground state normal mode vectors are computed with B3LYP functional in conjunction with different basis sets (see Figure S3 of supporting information). Our results demonstrate that none of these hybrid methods can predict correct relative intensity pattern of the key RR bands in the 210 nm (Bb state) excited spectrum of GMP. Though the method that computes normal modes at B3LYP/6‒311+G(2d,p)//PCM level predicts carbonyl stretching and ring breathing modes at 1689 and 1365 cm-1 respectively bearing maximum intensity, (Figure S3, panel b of supporting information) the other two methods (Figure S3, panel c and d of supporting information) fail. Moreover, a low intensity mode at 1539 cm-1 (Figure S3, panel a of supporting information) is predicted to be the most intense RR band in both of these computed spectra (Figure S3 panel c and d of supporting information). The method, employing augmented version of Dunning’s correlation consistent triple zeta basis set to compute GS normal modes (Figure S3, panel d) also fails similarly in comparison to the method that uses much smaller split valence 6-31G (d,p) basis set (Figure S3, panel c). These findings indicate that, the underlying problem is probably neither due to the choice of the density functional nor quality of the atom centered Gaussian basis set, but might be due to inadequacy of the structural model itself. To resolve this issue, RR spectra are computed on N9H‐Gua•7H2O model using identical method as used for isolated 9‐meG (Figure S4 of supporting information, and foot note there in). It is found that the predicted RR intensity of the most intense mode is of the band at 1365 cm-1 in all the three computed spectra, in agreement with experimental observation. The relative intensity of another intense band at 1580 cm-1 with respect to that of 1365 cm-1 is also predicted satisfactorily in all three computed spectra. Thus N9H‐Gua•7H2O model is able to predict relative RR intensity of the most intense bands of GMP irrespective of choice of basis set that was used to describe the ground state normal modes. This observation leads to the conclusion that, vibrational normal modes that are localized on exocyclic carbonyl, N1H and NH2 moieties mix in considerable amount with other internal coordinates of purine ring in presence of explicit water molecules (see Figure 2). This inherent mode-coupling of ground state normal modes ultimately affects, the vibrational 13 ACS Paragon Plus Environment


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wavenumbers, ground state PED, and projected excited state energy gradients, and thus the computed RR intensities. To further establish this fact, we compute RR spectrum of GMP in Bb state on three different model complexes where 9-meG is hydrogen bonded with decreasing number of water molecules, viz. 9-meG•6H2O, 9-meG•5H2O and 9-meG•4H2O (Figure 5). Optimized molecular structures of 9-meG•5H2O and 9-meG•4H2O are described in Figure S5, Table S5 and Table S6 of supporting information. We find that local solvation structure near NH2 moiety has large impact on relative RR intensities of vibrational modes that are even located far from C2 site, such as the carbonyl stretching vibration at 1689 cm-1. Though number of hydrogen bonds and relative position of two water molecules with respect to C=O moiety in all three models are intact, their directionalities change owing to cage structure of H-bonded solvation shell. In case of TD-B3LYP computed excited state gradients, omission of one water molecule (in 9-meG•5H2O) results in complete loss of intensity of the carbonyl stretching mode, (Figure 4c) and removal of two water molecules (in 9-meG•4H2O) entirely alters the relative intensity pattern of the whole RR spectrum (Figure 4d). This effect is independent of the choice of functional, as we find similar disagreement in computed intensities with experimental RR spectrum when the long-range corrected CAMB3LYP functional is used for evaluation of excited state gradient also (Figure S6 of supporting information). These findings suggest a counter-intuitive fact that, the FC region of the PES of electronic states of GMP-like conjugated heterocycles cannot be fully described by using density functionals that are reported to work well for excited state energies in similar system on an ad hoc basis. 9-meG•6H2O represents solvated GMP in best possible way for both - correct estimation of electronic excitation energies and prediction of intensities of key RR band. Figure 5 shows that, if four or five explicit water molecules are used to hydrate the base partially, a correct intensity pattern for the intense RR bands is not obtained. Completely wrong RR intensity is predicted for the most intense 1365 cm-1 band in the 210 nm excited spectrum. We found that contribution of two major internal coordinates; N9-C8 stretching and C5-N7-C8 bending toward PED of this normal mode is almost unchanged in isolated 9-meG, 9-meG•6H2O and 9-meG•4H2O. (Table S11 of supporting information) Nevertheless, the computed instantaneous cartesian forces on C2, N1, C6, C5, N7, and C8 atoms on 9-meG•4H2O model (Figure S7 of supporting information) are very different than those computed on fully hydrated 9meG•6H2O and N9H-Gua•7H2O, using all four functionals. (Figure S6 of supporting information) 14 ACS Paragon Plus Environment

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Although the two water molecules, removed from 9-meG•6H2O to obtain 9-meG•4H2O, make hydrogen bonds with the -NH2 moiety, affect the forces excreted on atoms on Bb state that are far located from the hydration site. Very low RR activity of the amino scissoring (at 1607 cm-1) mode which is expected to be affected most due to change in local solvation (in the 9-meG•4H2O or 9-meG•5H2O) is two folds. In isolated 9-meG, and partially solvated 9-meG the –NH2 group is pyramidalized with both the hydrogens being out of plane from remaining purine, (Table S7 of supporting information) and thus lending a lesser contribution towards pure ππ* Bb transition. Inclusion of explicit waters, not only make this group planar, but also reorganizes the PED profoundly. In presence of explicit water, contribution of ring stretching and bending coordinates increase at the expense of loss of contribution from –NH2 bending coordinate. (Table S11 of supporting information) A pyramidalized –NH2 also leads to a drastic change in direction of forces on N2 and C2 atoms. (Figure S7 of supporting information) For a correct RR activity of the amino scissoring mode, it is absolutely essential to hydrate the –NH2 moiety completely; thus both 9-meG•6H2O and N9HGua•7H2O produce appreciable intensity of this mode against isolated N9H-Gua and 9-meG models. (see Section E) Thus, the failure of partially hydrated 9-meG•4H2O or 9-meG•5H2O model is not solely ascribed to reorganization of ground state normal modes, but also to the wrong evaluation of the energy gradients on FC region on Bb state. We note that, being a single ring system, in uracil and other similar pyrimidines the extended effect of the H-bonded solvent molecules on normal modes that are far located from the hydration site might be not as important as double ring purine or other extended heteroaromatic systems. Thus, to capture the collective effect of explicit solvation, we use a completely hydrated model, 9-meG•6H2O complex for all comparison with results obtained on isolated 9-meGua. In the following sections, we describe features of computed RR spectrum on 9-meG•6H2O model in Lb and Bb electronic states vis-à-vis experimental spectrum. D. Simulation of RR Spectrum in Lb State We have used 9‐meG•6H2O model, for computation of RR spectra of GMP in the Lb singlet state. With 260 nm excitation, primarily five vibrational modes of GMP at 1322, 1363, 1486, 1577 and 1602 cm-1 becomes resonance enhanced.3,75 Major contribution for enhancement of these bands derive from Lb electronic state – a fact is ensured by comparing their relative intensities at 240 nm 15 ACS Paragon Plus Environment


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and 266 nm excited of RR spectrum.3 Performance of four density functionals namely B3LYP, PBE0, ωB97xD and CAM‐B3LYP have been assessed for computation of excited state gradients which are then used in simulation of RR spectra. For this purpose ground state normal modes are computed at B3LYP/6‒311+G(2d,p)//PCM level. Figure 6 compares computed spectra with these four functionals, and experimental spectrum obtained with 260 nm excitation.96 All four hybrid methods predict four modes at 1322, 1363, 1486, 1577 cm-1 bearing the most intensity, however B3LYP fails to reproduce the experimental pattern of relative intensities of 1322 and 1363 cm-1 bands. (Figure 6b, 6c, 6d and 6e) Moreover, B3LYP also cannot predict RR activity of C=O stretching mode (at 1689 cm-1) which is predicted at 1665 cm-1. The hybrid functional PBE0 containing 25 % Hatree‐Fock (HF) exchange and 75 % correlation weightage,97 compared to 20 % and 80 % of these components in B3LYP98 performs similarly but predicts C=O mode with moderate intensity. Both of these functionals overestimates intensity of N3‒C4 stretching mode coupled with N1H bending motion at 1577 cm-1. A key observation in all computed spectra is that exocyclic amino scissoring mode at 1602 cm-1 is not predicted to be RR active by these methods. We find CAM-B3LYP to perform well in computation of excited state gradients on Lb PES of GMP, and thus the RR spectrum. Dispersion corrected ωB97xD functional is also found to be similarly capable of predicting correct trend of the relative intensities of four major RR bands, specifically the relative intensities I1322/I1363 and I1486/I1577. Both of these functionals also predict moderate intensity of C=O stretching vibration, but are not able to predict RR activity of NH2 scissoring mode. CAM-B3LYP and ωB97xD, both are coulomb attenuated functionals containing 100 % non-local HF exchange for long range electron-electron interaction. Furthermore, along with long-range correction ωB97xD is also empirically dispersion corrected to account for noncovalent interaction in short range.99 In a recent study long range corrected CAM-B3LYP functional was found out to perform best for simulation of RR spectra of uracil in its first bright state.34 CAM‐B3LYP has been shown to describe excited state PES of charge transfer (CT) character correctly,100 while other hybrid functionals fail. The best functionals among all four tested ones for adequate prediction of overall relative intensities of the experimentally observed modes within 900-1800 cm-1 region are CAM-B3LYP and ωB97xD.


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In simulation of RR spectra of uracil within STA implicit polarizable continuum solvation model has been employed to account for bulk dielectric constant of water,34 and role of explicit solvation was also investigated in case of uracil and thymine by Sun and Brown.101 These authors investigated site-specific role of solvents, and find out that, explicitly H-bonded water molecule was necessary to predict the relative intensities of two carbonyl stretching modes (at 1623 and 1664 cm-1) with respect to the strongest mode of at 1235 cm-1 of uracil in 266 nm excited RR spectrum. GMP has complex structure of the surrounding solvents due to presence of six hydration sites, leading to a cage structure of the solvation shell, where explicit waters are H-bonded among themselves. In case of uracil and thymine in the earlier study, local solvation at every hydration site affected predicted RR intensity by reorganizing ground state normal modes. In case of GMP, instead of individual solvent at a particular site, the H-bonded cage of water molecules not only reorganize the local normal modes at hydration site, but also induces mixing of contribution of internal coordinates that are located far from exocyclic moiety. (see Table S11 in Supporting Information for quantitative PED of three models of GMP) One of such examples is the reorganization of amino scissoring mode at 1602 cm-1; in absence of explicit solvents this mode is solely (75 % contribution) a bending of HNH type vibration, but in presence of six explicit waters, it mixes with a another coordinate involving an explicit water in 9-meG•6H2O complex. Results obtained in the current study on GMP show that, if the polar carbonyl and amino moieties are explicitly solvated, the predicted relative intensities of the C=O stretching mode (at 1689 cm-1), and the two strong in-plane ring stretching modes (at 1365 and 1580 cm-1) agree reasonably well with experimental RR spectrum.

E. Simulation of RR Spectrum in Bb State 210 nm excited RR spectrum of GMP in Bb electronic state (Figure 7a) is characterized by intense ring stretching modes at 1176, 1365 and 1580 cm-1, NH2 scissoring vibration at 1607 cm-1, and C=O str. mode at 1689 cm-1.3 Computed RR spectra on four models with excited state gradient evaluated with CAM‐B3LYP and B3LYP functionals are described in Figure 7 and Figure 8 respectively. Apart from isolated N9H‐Gua, three other models correctly predict 1365 cm-1 mode as the most intense RR band. Although CAM‐B3LYP functional applied on 9‐meG•6H2O complex produces relative intensity pattern in good agreement with experimental spectrum in Lb state, (Figure 6c) underestimates intensity of the exocyclic amino scissoring mode in the Bb state (Figure 17 ACS Paragon Plus Environment


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7b). CAM‐B3LYP functional overestimates intensity of carbonyl stretching mode for isolated 9‐meG, but significantly underestimates the same in case of all the explicitly solvated models. (Figure 7b and 7d) Alteration of ground state normal mode in 9‐meG•6H2O in comparison with that of isolated 9-meG (Figure 4) is ruled out as possible reason, because C=O stretching mode is predicted with considerable intensity for the same complex when gradient is computed with the B3LYP functional. (Figure 8b and 8d) We find that choice of functional for evaluation of excited state gradient affects the computed spectra on N9H‐Gua•7H2O by least amount. (Figure 7e and Figure 8e) The most intense band of GMP at 1365 cm-1 in the 210 nm excited spectra becomes of negligible intensity when excited with 260 nm. This band has been assigned to a normal mode comprising of stretching of C5‒N7 and C8‒N9 bonds, coupled with N9H bending previously.61 McNaughton and coworker have assigned this band to ring stretching vibration with concomitant bending of C8–H and N9–H in isolated guanine.47 However, assignment of this band is done to a different normal mode composed of stretching of C2–N2 bond, bending of N1–H and rocking motion of NH2 moiety in guanine heptahydrate.47 This mode draws maximum intensity when excited within Bb electronic transition. Transition dipole of Bb state polarizes π electron density (Figure 1) along the long axis of the pyrimidine ring, i.e. the line joining C8 atom and center of N1‒C2 bond. Thus, this band is likely to be associated with an in plane ring deformation along the same direction. In our computation this mode is found to be at 1377 cm˗1 for 9˗meG•6H2O (Table S9), similar to the mode of isolated guanine reported in the earlier study.61 We find intensity of amino scissoring mode at 1607 cm-1 and pyrimidine deformation mode coupled with N1–H bending at 1580 cm-1 are strongly dependent on choice of solvated model complex. In case of the isolated base, both of the B3LYP and CAM‐B3LYP functionals predict very low RR intensity of exocyclic NH2 scissoring mode. (Figure 7c-d and 8c-d) In the watercomplexed models (9‐meG•6H2O and N9H‐Gua•7H2O), B3LYP predicts moderate intensity of this mode, while CAM-B3LYP underestimates the same. It is important to note here that, NH2 moiety is non-planar in both of the isolated models, but introduction of the H-bonded water molecules makes it nearly planar.


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Similar to carbonyl stretching mode, intensity of 1580 cm-1 band is also largely underestimated by CAM‐B3LYP functional in 9‐meG•6H2O, but is of highest intensity in N9H‐Gua•7H2O model. (Figure 7b and 7c) On the other hand B3LYP predicts correct trend of relative intensity of 1580 and 1607 cm-1 for 9‐meG•6H2O model (Figure 8b). B3LYP and CAMB3LYP computed relative intensities of three moderately intense bands of GMP at 866 cm-1, 1078 cm-1 and 1176 cm-1 are not correctly predicted on 9‐meG•6H2O model but shows good agreement with experiment when computed on N9H‐Gua•7H2O model. Surprisingly, we find that, dispersion and long range corrected ωB97xD functional that was able to predict relative intensities of intense RR bands of GMP in Lb state correctly, fails to do so in the Bb excited state. This is attributed to the failure of this functional in correct evaluation of FC gradients on PES of Bb state for 9‐meG•6H2O model (Figure S2, panel p of supporting information). For all four structural models investigated, we find that, ωB97xD computed excited state forces on N1, N3, N7, N9 and C5 atoms are significantly different from those computed with either B3LYP or CAM-B3LYP functionals for Bb state. (Figure S2, panel m-p of supporting information). This suggests ωB97xD functional might not be suitable for exploring PES of high lying valence states of pi-conjugated heterocycles. The transition dipole of Bb excitation is aligned along nearly perpendicular to the C=O stretching coordinate. But, considerable RR activity of the C=O stretching mode (at 1689 cm-1) at 210 nm (Bb state) excitation indicates, probable enhancement through Albrecht’s B term or Hertzberg-Teller effect through dependence of the electronic transition moment on the vibrational coordinate.10 This mode can borrow intensity also through interference from nearby high lying electronic state at 186 nm also. None of these effects is accounted for in the STA approach. Effect of interference from nearby electronic states can be accounted for at amplitude level by weightedgradient method within STA formalism,38 and through time-independent sum-over-states approach.102 Vibronic effect was shown to be important for RR activity of low frequency modes below 700 cm-1 in extended π-conjugated system such as rhodamine 6G and iron(II) porphyrin with imidazole and CO ligands.24 However, for uracil, Jensen and coworkers have shown that while absolute RR intensities computed via vibronic theory is in better agreement with experimental RR cross-section than that computed through STA approximation, the relative RR intensities computed from both the approaches are similar.24 19 ACS Paragon Plus Environment


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F. Role of Choice of Functionals and Caveats A common finding of several studies on application of TD-DFT is that, range separated functionals (CAM-B3LYP, wB97x etc.) that contain more amount of HF exchange in long-range than that at short-range always perform better than any GGA functionals (B3LYP, PBE0 etc.) for excited states having CT character in extended π-conjugated system.103 We find that this knowledge about the choice of functionals do not translate to simulation of RR spectra within excited state gradient (or STA) approach. Simulation of RR intensities of GMP in two distinct electronic states (Lb ~ 248 nm and Bb ~ 210 nm) provides with unique opportunity to asses performance of different hybrid functional for evaluation of excited state gradients. We employ four density functionals; viz., hybrid PBE0,104 hybrid GGA B3LYP,98,105 long-range corrected CAM-B3LYP106 and long-range and dispersion corrected ωB97xD99 to compute the excited state gradients in this study. Previously Brown and co-workers have concluded that hybrid methods of computing excited state gradient with CAM-B3LYP, long range corrected BLYP (LC-B3LYP), and with spin flip-TD-DFT in conjunction with BHHLYP (modified BLYP with 50% HF exchange) functionals produce best result for prediction of RR spectra in the first bright state of uracil.34 We observe that B3LYP, PBE0, CAM-B3LYP and ωB97xD perform satisfactorily and very similarly in case of low energy Lb state, but both the long-range corrected CAM-B3LYP and ωB97xD functional perform poorly for high lying Bb state of GMP. All four functionals predict the one electron description of Lb state as a pure H→L+1 configuration in agreement with high level ab initio results. The similarity in computed RR spectra (in Figure 6, panel b-e) in Lb state stems from the fact that, the cartesian forces (in magnitude and direction) exerted on the heavy nuclei of 9‐meG•6H2O model obtained with all four functionals are very similar. (Figure 4, panel d, h, i, p) However, complexity of the situation becomes manifold when analyzing RR spectrum in the Bb state. We find that performances of different functionals are greatly influenced by choice of the model complex also, especially the number and orientation of water molecules that hydrate the chromophore through explicit H-bonding interactions. We find that, while TD-B3LYP predicts Bb state with a major (88 %) orbital contribution of H‒1→L type, other three functionals predict a mixed orbital contribution of H−1→L and H→L+5 in all explicitly solvated models. (Figure S7 of supporting information) The inability of these three functionals to describe the one electron configuration of Bb transition as a pure H−1→L contribution could be ascribed to their failure for


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prediction of RR spectrum in this state to some extent. We observe that, as soon as one (9‐meG•5H2O) or two (9‐meG•4H2O) water molecules are removed from 9‐meG•6H2O model, the instantaneous Bb state cartesian forces on heavy atoms change in drastic way from one functional to another, and also between different GMP models. Thus, the specific role of a functional and/or specific structural model on the predicted RR intensity cannot be done in a straightforward manner.

Computation of RR intensity require knowledge of the normal-mode displacements on the excited-state PES from the ground-state minimum. From a pure computational perspective, evaluation of excited state gradients at FC geometry is far less resource consuming than performing rigorous geometry optimization on PES of electronic excited state. Excited state geometry optimization, specifically of the high lying Bb state, required for the application of rigorous adiabatic approach for computation of RR intensity, is challenging because of occurrence of state crossings. During geometry optimization within TD-DFT formalism, it is also extremely difficult to follow the Bb electronic state near 210 nm, due to presence of multiple electronic states which are within 0.2-0.4 eV in energy of each other. Even, geometry optimization in the lowest energy La and Lb states in GMP, and in all nucleobases in very challenging due to occurrence of conical intersection. State crossing through these conical intersections results in ultrafast relaxation (in less than 300 fs) of excited states near 260 nm in all naturel nucleobases. Thus, complete vibronic analysis through evaluation of excited state hessian in these systems is extremely challenging. Although, vertical gradient approach such as STA cannot take into account any of the nondiabetic effects, it provides an attractive theoretical framework, to interpret experimental RR spectra in terms of (i) instantaneous FC force excreted on each nuclei, and (ii) ground state normal modes. Henceforth, we apply IMDHO model and short-time dynamics approximation of RR spectroscopy on a two-ring π system like GMP, and find that, RR activities strongly depend on the micro-solvated structure of the chromophore through both modulation of ground state normal modes, and FC gradients on electronic excited states. We believe that qualities of the simulated RR spectrum in this approach would improve if several solvent conformations of the first solvation shell surrounding the chromophore are sampled from a classical molecular dynamics simulation. In this scenario, the final RR spectrum would be obtained by averaging the RR intensities 21 ACS Paragon Plus Environment


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computed on each of the energy optimized ground state chromophore structure, which is hydrated by different solvent configurations.

Conclusion Computed within STA approach, the RR intensities of intense ring stretching modes of GMP are found to be strongly influenced by ground state normal mode vectors and wavenumbers; both of which are strongly governed by the immediate solvent environment. Specifically, RR intensities and harmonic vibrational wavenumbers of two exocyclic modes, viz. carbonyl stretching at 1689 cm-1 and -NH2 scissoring at 1607 cm-1 are found to be strongly dependent on the number and direction of explicit H-bonding interactions within the first solvation shell. We find that reorganization of ground state normal modes, and the magnitude and absolute directions of the energy gradients on excited state PES affect the computed RR intensity of the ring stretching modes of GMP in a non-intuitive manner. We show shat, if partially solvated, (with four or five water molecules) the resulting structural models fail to predict the correct RR activity for the intense ring mode at 1365 cm-1, mainly due to wrong evaluation of cartesian gradients on Bb state, in comparison to GMP which is solvated at all hydration sites with six water molecules. In a counterintuitive manner, B3LYP was found to perform better than long range corrected CAM‐B3LYP, and additionally dispersion corrected ωB97xD functionals for prediction of RR intensities in the high energy Bb state of GMP. This is attributed to the failure of the later functionals in correct prediction of the instantaneous cartesian forces in the FC region of the PES of Bb electronic state. Our results imply that construction of a physical model preserving important water-chromophore interactions is a prerequisite for benchmarking any theoretical method for predicting spectroscopic observables, such as, RR intensities. Herein described case study on GMP establishes that, the predicted RR intensities do not simply depend on the choice of the density functional, the basis set or implicit solvation, but on the adequacy of the structural model of the exclusively hydrated chromophore.

Supporting Information Seven additional figures and eleven tables showing relative accuracy of different models for predicting ππ* singlet states energies, direction of computed cartesian forces on Bb state with four functionals, dependence of computed RR spectrum on choice of basis set, computed RR spectra of Bb state with other functional, computed forces on Bb state with four functionals on partially 22 ACS Paragon Plus Environment

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solvated models of GMP, Cartesian coordinates of all models on ground electronic state, experimental and computed harmonic vibrational frequencies on different models, character of electronic excitations computed with additional density functionals, quantitative PED of key vibrational modes of GMP.

Acknowledgement SM thanks Jawaharlal Nehru Centre for Advanced Scientific Research, India, and Weizmann Institute of Science, Israel for computing resources.

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Figures

Figure 1. Molecular structure of four models of GMP : (a) 9-meG•6H2O, (b) 9-meG, (c) N9H-Gua and (d) N9H-Gua•7H2O in solution and energy minimized at B3LYP/6-311+G(2d,p) level of theory. All the hydrogen bonds (Å) between the base and surrounding water molecules are shown with dashed lines. Conventional numbering of ring atoms is indicated in (a). Directions of computed transition dipole moments for Lb, Bb and S11 states are shown with bold arrows. Indicated magnitude of the transition dipole moment vectors is magnified by a factor of 3.5 over the calculated value for improved visualization. Panel (a) is adapted with permission from Ref 50. Copyright (2017, American Chemical Society).



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Figure 2. Computed normal modes of GMP on four different models at B3LYP/6311+G(2d,p)//PCM level of theory. (a-d) carbonyl stretching vibration (1689 cm-1 in experiment), contribution of C=O internal coordinate decreases with inclusion of explicit water molecules;(eh) in-plane ring deformation vibration (1486 cm-1 in experiment), methyl at N9 reduces amount of stretching of N7‒C8 coordinate; (i-l) pyrimidine breathing mode (1365 cm-1 in experiment), N1H bending contribution disappears due to hydrogen bonding with water at that site and heavy methyl group at N9 alters direction of relative movement of C5 atom. Chemcraft v1.6 is used to visualize and plot the normal mode vectors.


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Figure 3. Kohn-Sham molecular orbitals (MO) involved in (a) La , (b) Lb and (c) Bb and S11 electronic transitions of GMP. MOs are computed on 9-meGua•6H2O complex at B3LYP/6311+G(2d,p)//PCM level of theory and contribution (in %) associated with one electron configuration of each transition is computed at TD-B3LYP/6-311+G(2d,p)//PCM level of theory. Experimental transition energies (in nm) are mentioned for each computed excited state of GMP. H and L stands for HOMO and LUMO orbital respectively. Panel (c) is adapted with permission from Ref 50. Copyright (2017, American Chemical Society).



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Figure 4. Direction of cartesian forces on atoms of GMP in FC region of Lb electronic state, computed on four models with (a-d) B3LYP; (e-h) CAM-B3LYP; (i-l) PBE0 and (m-p) ωB97xD functionals. Ground state structure was optimized with B3LYP functional. Both ground state normal modes and excited state gradients are computed with 6-311+G(2d,p) basis set and PCM implicit solvation. In all model Lb state was predicted to be second singlet (S2) in calculated state order (see Table 1 and Table S10). Oscillator strengths (f) and orbital contribution in each transitions are mentioned, H and L stand for highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) respectively.


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Figure 5. Effect of structure of the first solvation shell on computed RR spectra of GMP in Bb state. RR spectra are computed on (b) 9-meG•6H2O, (c) 9-meG•5H2O and (d) 9-meG•4H2O model complex with TD-B3LYP derived excited state gradients. The experimental spectrum at top (a) in both panels is of 1 mM GMP (in water, pH 6.8) with 210 nm excitation wavelength. For calculation of these spectra ground state normal modes of all four models are computed with B3LYP functional. For evaluation of excited state gradients same basis set was used. All ground and excited state calculations are performed with 6-311+G(2d,p) basis set and PCM as implicit solvation model. Lorentzian line-shape with FWHM of 15 cm-1 is used for generating spectra form computed intensities. No frequency scaling was used. The experimental 210 nm excited RR spectrum of GMP is adapted from ref 96 with permission.



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Figure 6. Computed RR spectra of 9-meG•6H2O model in Lb electronic state using excited state gradients evaluated with (b) B3LYP, (c) CAM-B3LYP, (d) ωB97xD and (e) PBE0 functionals. The experimental spectrum of GMP (500 μM, miliQ Water, pH 6.8) at 260 nm excitation wavelength in shown in panel (a). These spectra are computed with ground state normal modes evaluated at B3LYP/6-311+g(2d,p)//PCM level of theory. All ground and excited state calculations are performed with 6-311+G(2d,p) basis set and PCM as implicit solvation model. Lorentzian line-shape with FWHM of 15 cm-1 is used for generating spectra form computed intensities. No frequency scaling was used. The band at 1048 cm-1 in panel (a) is from sodium nitrate that was used as internal intensity standard. The experimental 260 nm excited RR spectrum of GMP is adapted from ref 96 with permission.


Page 37 of 41 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 7. Computed RR spectra of in Bb electronic state with TD-CAM-B3LYP derived excited state gradients. (a) 210 nm excited experimental spectrum of GMP (1 mM, miliQ Water, pH 6.8), and RR spectra computed on (b) 9-meG•6H2O, (c) N9H-Gua•7H2O, (d) 9-meG and (e) N9G-Gua model. For calculation of these spectra ground state normal modes of all four models are computed with B3LYP functional. All ground and excited state calculations are performed with 6311+G(2d,p) basis set and PCM as implicit solvation model. Lorentzian line-shape with FWHM of 15 cm-1 is used for generating spectra form computed intensities. No frequency scaling was used. The experimental 210 nm excited RR spectrum of GMP is adapted from ref 96 with permission.



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Figure 8. Computed RR spectra of in Bb electronic state with TD-B3LYP derived excited state gradients. (a) 210 nm excited experimental spectrum of GMP (1 mM, miliQ Water, pH 6.8), and RR spectra computed on (b) 9-meG•6H2O, (c) N9H-Gua•7H2O, (d) 9-meG and (e) N9H-Gua model. For calculation of these spectra ground state normal modes of all four models are computed with B3LYP functional. All ground and excited state calculations are performed with 6311+G(2d,p) basis set and PCM as implicit solvation model. Lorentzian line-shape with FWHM of 15 cm-1 is used for generating spectra form computed intensities. No frequency scaling was used. The experimental 210 nm excited RR spectrum of GMP is adapted from ref 96 with permission.


Page 39 of 41 1 2 3 4 5 6 7 8 9 10 11 12 13 Type 14 15 16 La 17(ππ*) 18 Lb 19(ππ*) 201nπ* 21 22 Bb 23(ππ*) 24 ππ* 25 26 ππ* 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Table 1. Computed vertical singlet excitation energies (ΔE in nm and eV), oscillator strengths (fPCM) and major orbital contribution1 to each electronic transition on three models of GMP by TDB3LYP method with 6-311+G(2d,p) basis set and PCM solvation.

9‐meG•6H2O2

State order

Major orbital Contribution1 (%)

S1

H→L (95)

S2

H→L+1 (95)

S4

H−2→L (81)

S8

H-1→L (88)

S10

H→L+6 (86)

S11

H−3→L (91)

∆Evert,PC M

eV (fPCM) 4.49 (0.24) 4.95 (0.52) 5.62 (0.0005) 5.97 (0.35) 6.27 (0.006) 6.28 (0.17)

N9H‐Gua•7 H2O2

N9H‐Gua2

∆Evert,PCM eV (fPCM)

∆Evert,PCM eV (fPCM)

4.60 (0.15)

4.79 (0.14)

5.17 (0.34)

5.11 (0.35)

5.64 (0.0004)

5.48 (0.0001)

6.26 (0.25)

6.56 (0.26)

6.35 (0.008) 6.39 (0.13)

6.97 (0.22)

Exp7

N9H‐Gua, published CASSCF/CASPT2 ∆E (f)3 4.73 (0.15) 5.11 (0.24) 5.98 (0.02) 6.49 (0.29) 6.59 (0.18) 6.72 (0.41)

LR-TD-DFT

Real-time TD-DFT

ΔEExp eV

CSF3 (weights)

∆Evert4

ΔE5

ΔE6

H→L (68)

4.65

4.86

4.46

4.47

H→L+1 (69)

5.10

5.17

4.71

5.00

5.64

5.58

6.23

6.21

6.53

6.63

5.53 H-1→L (51) H-1→L+1 (14)

1Percentages

contributions are calculated as 100 x twice the squares of the coefficients in the CI expansion of TDDFT wave functions; 2TD-DFT with cluster-continuum model; 3Ref. 85, using CASSCF//CASPT2; 4Ref. 48, vertical excitation energy is computed with cluster continuum model containing explicit water molecules at TD-X3LYP/aug-cc-pVDZ//PCM level theory at B3LYP/def-SVP optimized geometries; 5Ref. 90, using TD-B3LYP/6-311(3+,3+)G(df,pd)//vacuo; 6Ref. 91, using real-time TD-DFT/NAOs//vacuo; 7Average experimental transition energies are derived from absorption in liquid, linear dichroism, circular dichroism, magnetic circular dichroism, and polarized absorption spectroscopy experiments, see Ref. 85 for details. Abbreviation; NAO, numerical atomic orbitals, CSF, configuration state functions at CASASCF/CASPT2 level, LR, linear response.



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