Solvent Fluctuations and Nuclear Quantum Effects Modulate the Molecular Hyperpolarizability of Water Chungwen Liang,1, 2, ∗ Gabriele Tocci,1, 2 David M. Wilkins,1, 2 Andrea Grisafi,1 Sylvie Roke,2 and Michele Ceriotti1 1Laboratory of Computational Science and Modeling, Institute of Materials, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland 2Laboratory for fundamental BioPhotonics, Institutes of Bioengineering and Materials Science and Engineering, School of Engineering, and Lausanne Centre for Ultrafast Science, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland Second-Harmonic Scatteringh (SHS) experiments provide a unique approach to probe non- centrosymmetric environments in aqueous media, from bulk solutions to interfaces, living cells and tissue. A central assumption made in analyzing SHS experiments is that the each molecule scatters light according to a constant molecular hyperpolarizability tensor β(2). Here, we investigate the dependence of the molecular hyperpolarizability of water on its environment and internal geometric distortions, in order to test the hypothesis of constant β(2). We use quantum chemistry calculations of the hyperpolarizability of a molecule embedded in point-charge environments obtained from sim- ulations of bulk water. We demonstrate that both the heterogeneity of the solvent configurations and the quantum mechanical fluctuations of the molecular geometry introduce large variations in the non-linear optical response of water. This finding has the potential to change the way SHS experiments are interpreted: in particular, isotopic differences between H2O and D2O could explain recent SHG scattering observations. Finally, we show that a simple machine-learning framework can predict accurately the fluctuations of the molecular hyperpolarizability. This model accounts for the microscopic inhomogeneity of the solvent and represents a first step towards quantitative modelling of SHS experiments. Nonlinear optical (NLO) processes are of great inter- terfaces or in the bulk phase, it is common to assume est in physics, chemistry, biology and materials science, that scattering from molecules in solution is incoherent as they provide a means of probing the structure and [6, 9, 16]. However, recent experiments and simulations behavior of liquids, nanostructures and interfaces [1, 2]. have found evidence of a significant coherent contribution Second harmonic generation (SHG) is a NLO process in to the scattering, particularly in the case of hydrogen- which two photons with frequency ! are instantaneously bonded solvents. [17–20] Another critical assumption combined to generate new photons with frequency 2! af- that is often made is that the hyperpolarizability ten- ter interacting with a material. As a second-order NLO sor β(2) of the molecules is constant, independent of the process, SHG is only allowed in non-centrosymmetric en- environment and the molecular geometries. Most exper- vironments. SHG spectroscopy experiments in molecu- imental analyses rely on electronic structure calculations lar systems can be carried out in three different geome- to obtain an estimate of β(2). Early computational stud- tries: reflection, transmission, and scattering (SHS) [3– ies focused on calculating this microscopic quantity for 5]. The properties of planar interfaces are often probed gas-phase molecules [21–23], while more recently the role by SHG spectroscopy in the reflection mode, while the of solvation has also been considered [24–26]. properties of spherical interfaces and bulk materials are Due to its ubiquitous presence in chemical and bio- often probed by SHG spectroscopy in the scattering mode logical systems, water has been given special attention [6, 7]. The structural information of molecular systems, in experimental and theoretical SHS studies. As a con- such as molecular adsorption and orientation on metal sequence of the strong electrostatic interactions in the surfaces [3, 8], polarity of liquid interfaces [9], nanoparti- liquid, the electronic structure of water and therefore cles in solutions [10, 11] and bulk molecular liquids [12], its molecular hyperpolarizability change dramatically on has been intensively studied by SHG spectroscopy. going from the gas phase to the liquid phase [27, 28]. arXiv:1705.01649v1 [physics.chem-ph] 3 May 2017 Theoretical frameworks for estimation of the SHG To determine these changes quantitatively, several quan- response in the reflection and scattering modes have tum chemistry calculations have been performed based long been known [13, 14], and are necessary to in- on simple point charge environments [26], dielectric con- terpret experimental results. The SHS response of a tinuum theories [29], solvation models [30], and mixed molecular system simultaneously carries information on quantum/classical (QM/MM) approaches [29, 31] to in- the structural correlations and the nonlinear optical corporate the environmental effect. Even though the response of each molecule, and modelling is required value of the hyperpolarizability is very sensitive to the to disentangle these contributions to the experimental level of theory, functional and basis set, all of these stud- measurements[15]. However, it is challenging to do so ies report a sign change of the elements of β(2) upon without introducing harsh approximations. For instance, changing from a gas phase environment to the liquid to extract information on orientational correlations at in- phase. Despite the fact that a strong dependence on 2 the molecular configurations used in the calculations has 10 -53 (C 3 m 3 J -2 ) been reported [32], most theoretical studies have assumed -64 -32 0 32 64 that the water hyperpolarizability tensor elements are constant [26, 29–31, 33], and thus independent of the (a) inhomogeneous liquid environment or the internal geom- βzxx etry of the water molecule. It should, however, be noted βzyy that in the most commonly adopted description the SHS βzzz process is assumed to take place instantaneously, so that each water molecule should respond according to its en- vironment. Only by simultaneously taking into account Distribution the structural correlations between molecules [20, 33] and the variation of their second-harmonic response would it be possible to reach an approximate quantitative descrip- tion of SHS experiments. (b) z In this paper we investigate the hyperpolarizability of βxxx βxzz water molecules in the liquid phase, and demonstrate βxxy βyyy that the inhomogeneous electrostatic environment has a β x βxyy yzz dramatic impact on the elements of β(2). We also con- βxyz sider the role played by thermal and quantum fluctua- y tions of the internal coordinates of each molecule, finding Distribution evidence for a significant isotope effect between H2O and D2O. Finally, we establish a theoretical framework that allows us to combine an accurate quantum mechanical -20 -10 0 10 20 evaluation of the second-order response with a machine- Atomic units learning model that can accurately predict the behavior of molecules in large-scale molecular dynamics simula- FIG. 1. (a) The distributions of three tensor elements βzxx, tions. We envision that this framework will facilitate the βzyy and βzzz. For comparison, the constant gas phase values calculation of the full SHS intensity from atomistic sim- are shown as dashed lines. (b) The distributions of the re- ulations, which we leave for future work. maining seven tensor elements. Inset: the orientation of the In order to investigate the role of solvent fluctuations in central water molecule. determining the hyperpolarizability of a water molecule in the liquid phase we use an embedding approach in- element β is given by the numerical derivative of the spired by QM/MM methods, where the hyperpolarizabil- ijk energy U with respect to the external electric fields Ei, ity of a central water molecule is treated quantum me- E , and E : chanically, whereas the surrounding molecules are treated j k classically. We first perform extensive, long-time and @3U large-scale molecular dynamics (MD) simulations of bulk βijk = : (1) @Ei@Ej@Ek liquid water using fixed point charge models [34, 35] (see Supporting Information for the simulation details). From We calculate the static hyperpolarizability tensor, which the results of these simulations we extract random con- is an approximation to the full frequency dependent ten- figurations of water environments, by taking molecules sor probed in SHS experiments. For aqueous systems at within 1.5 nm of a central water molecule. We show the frequencies typically used in elastic second-harmonic in the SI that this cutoff is sufficient to provide a rep- scattering experiments this approximation can be ex- resentative sampling of the electrostatic environment in pected to entail an error smaller than 10% [30] – which bulk water. We perform quantum chemistry calculations should not affect the qualitative scope of our discussion of the hyperpolarizability tensor of the central molecule, of the assessment and the machine-learning of the local with the surrounding molecules modelled as point charges fluctuations of β(2). consistent with the empirical force-field. Since our ob- The distributions of βzxx, βzyy and βzzz are shown in jective here is to assess the importance of fluctuations Figure 1(a), and compared to the values for a (rigid) gas- on the molecular hyperpolarizability of water, and to de- phase molecule. It can be seen that these elements have velop a computational framework that is compatible with