Modeling UV/Vis Absorption Spectra of Food Colorants in Solution: Anthocyanins and Curcumin as Case Studies.

We present a comprehensive computational study of UV/Vis absorption spectra of significant food colorants, specifically anthocyanins and curcumin tautomers, dissolved in polar protic solvents, namely water and ethanol. The absorption spectra are simulated using two fully polarizable quantum mechanical (QM)/molecular mechanics (MM) models based on the fluctuating charge (FQ) and fluctuating charge and dipoles (FQFµ) force fields. To accurately capture the dynamical aspects of the solvation phenomenon, atomistic approaches are combined with configurational sampling obtained through classical molecular dynamics (MD) simulations. The calculated QM/FQ and QM/FQFµ spectra are then compared with experiments. Our findings demonstrate that a precise reproduction of the UV/Vis spectra of the studied pigments can be achieved by adequately accounting for configurational sampling, polarization effects, and hydrogen bonding interactions.

UV-Resonance Raman Spectra of Systems in Complex Environments: A Multiscale Modeling Applied to Doxorubicin Intercalated into DNA.

UV-Resonance Raman (RR) spectroscopy is a valuable tool to study the binding of drugs to biomolecular receptors. The extraction of information at the molecular level from experimental RR spectra is made much easier and more complete thanks to the use of computational approaches, specifically tuned to deal with the complexity of the supramolecular system. In this paper, we propose a protocol to simulate RR spectra of complex systems at different levels of sophistication, by exploiting a quantum mechanics/molecular mechanics (QM/MM) approach. The approach is challenged to investigate RR spectra of a widely used chemotherapy drug, doxorubicin (DOX) intercalated into a DNA double strand. The computed results show good agreement with experimental data, thus confirming the reliability of the computational protocol.

A polarizable three-layer frozen density embedding/molecular mechanics approach.

We present a novel multilayer polarizable embedding approach in which the system is divided into three portions, two of which are treated using density functional theory and their interaction is based on frozen density embedding (FDE) theory, and both also mutually interact with a polarizable classical layer described using an atomistic model based on fluctuating charges (FQ). The efficacy of the model is demonstrated by extending the formalism to linear response properties and applying it to the simulation of the excitation energies of organic molecules in aqueous solution, where the solute and the first solvation shell are treated using FDE, while the rest of the solvent is modeled using FQ charges.

Effective yet reliable computation of hyperfine coupling constants in solution by a QM/MM approach: Interplay between electrostatics and non-electrostatic effects.

In this paper, we have extended to the calculation of hyperfine coupling constants, the model recently proposed by some of the present authors [Giovannini et al., J. Chem. Theory Comput. 13, 4854-4870 (2017)] to include Pauli repulsion and dispersion effects in Quantum Mechanical/Molecular Mechanics (QM/MM) approaches. The peculiarity of the proposed approach stands in the fact that repulsion/dispersion contributions are explicitly introduced in the QM Hamiltonian. Therefore, such terms not only enter the evaluation of energetic properties but also propagate to molecular properties and spectra. A novel parametrization of the electrostatic fluctuating charge force field has been developed, thus allowing a quantitative reproduction of reference QM interaction energies. Such a parametrization has been then tested against the prediction of EPR parameters of prototypical nitroxide radicals in aqueous solutions.

Effective computational route towards vibrational optical activity spectra of chiral molecules in aqueous solution.

We present a computational methodology based on a polarizable Quantum Mechanical (QM)/Molecular Mechanics (MM) approach to accurately compute the Vibrational Optical Activity (VOA) spectra of chiral systems. This approach is applied for the calculation of Infrared (IR), Vibrational Circular Dichroism (VCD), Raman and Raman Optical Activity (ROA) spectra of aqueous solutions of (l)-methyl lactate and (S)-glycidol. Remarkable agreement between calculations and experiments is reported, showing the reliability and accuracy of the methodology, especially with respect to standard continuum solvation approaches.

Multiscale Frozen Density Embedding/Molecular Mechanics Approach for Simulating Magnetic Response Properties of Solvated Systems.

We present a three-layer hybrid quantum mechanical/quantum embedding/molecular mechanics approach for calculating nuclear magnetic resonance (NMR) shieldings and J-couplings of molecular systems in solution. The model is based on the frozen density embedding (FDE) and polarizable fluctuating charges (FQ) and fluctuating dipoles (FQFµ) force fields and permits the accurate ab initio description of short-range nonelectrostatic interactions by means of the FDE shell and cost-effective treatment of long-range electrostatic interactions through the polarizable force field FQ(Fµ). Our approach's accuracy and potential are demonstrated by studying NMR spectra of Brooker's merocyanine in aqueous and nonaqueous solutions.

Multiscale modeling of surface enhanced fluorescence.

The fluorescence response of a chromophore in the proximity of a plasmonic nanostructure can be enhanced by several orders of magnitude, yielding the so-called surface-enhanced fluorescence (SEF). An in-depth understanding of SEF mechanisms benefits from fully atomistic theoretical models because SEF signals can be non-trivially affected by the atomistic profile of the nanostructure's surface. This work presents the first fully atomistic multiscale approach to SEF, capable of describing realistic structures. The method is based on coupling density functional theory (DFT) with state-of-the-art atomistic electromagnetic approaches, allowing for reliable physically-based modeling of molecule-nanostructure interactions. Computed results remarkably demonstrate the key role of the NP morphology and atomistic features in quenching/enhancing the fluorescence signal.

Correction to "Going Beyond the Limits of Classical Atomistic Modeling of Plasmonic Nanostructures".

[This corrects the article DOI: 10.1021/acs.jpcc.1c04716.].

QM/Classical Modeling of Surface Enhanced Raman Scattering Based on Atomistic Electromagnetic Models.

We present quantum mechanics (QM)/frequency dependent fluctuating charge (QM/ωFQ) and fluctuating dipoles (QM/ωFQFµ) multiscale approaches to model surface-enhanced Raman scattering spectra of molecular systems adsorbed on plasmonic nanostructures. The methods are based on a QM/classical partitioning of the system, where the plasmonic substrate is treated by means of the atomistic electromagnetic models ωFQ and ωFQFµ, which are able to describe in a unique fashion and at the same level of accuracy the plasmonic properties of noble metal nanostructures and graphene-based materials. Such methods are based on classical physics, i.e. Drude conduction theory, classical electrodynamics, and atomistic polarizability to account for interband transitions, by also including an ad-hoc phenomenological correction to describe quantum tunneling. QM/ωFQ and QM/ωFQFµ are thus applied to selected test cases, for which computed results are compared with available experiments, showing the robustness and reliability of both approaches.

Absorption Properties of Large Complex Molecular Systems: The DFTB/Fluctuating Charge Approach.

We report on the first formulation of a novel polarizable QM/MM approach, where the density functional tight binding (DFTB) is coupled to the fluctuating charge (FQ) force field. The resulting method (DFTB/FQ) is then extended to the linear response within the TD-DFTB framework and challenged to study absorption spectra of large condensed-phase systems.

Do We Really Need Quantum Mechanics to Describe Plasmonic Properties of Metal Nanostructures?

Optical properties of metal nanostructures are the basis of several scientific and technological applications. When the nanostructure characteristic size is of the order of few nm or less, it is generally accepted that only a description that explicitly describes electrons by quantum mechanics can reproduce faithfully its optical response. For example, the plasmon resonance shift upon shrinking the nanostructure size (red-shift for simple metals, blue-shift for d-metals such as gold and silver) is universally accepted to originate from the quantum nature of the system. Here we show instead that an atomistic approach based on classical physics, ωFQFµ (frequency dependent fluctuating charges and fluctuating dipoles), is able to reproduce all the typical "quantum" size effects, such as the sign and the magnitude of the plasmon shift, the progressive loss of the plasmon resonance for gold, the atomistically detailed features in the induced electron density, and the non local effects in the nanoparticle response. To support our findings, we compare the ωFQFµ results for Ag and Au with literature time-dependent DFT simulations, showing the capability of fully classical physics to reproduce these TDDFT results. Only electron tunneling between nanostructures emerges as a genuine quantum mechanical effect, that we had to include in the model by an ad hoc term.

Going Beyond the Limits of Classical Atomistic Modeling of Plasmonic Nanostructures.

Theoretical modeling of plasmonic phenomena is of fundamental importance for rationalizing experimental measurements. Despite the great success of classical continuum modeling, recent technological advances allowing for the fabrication of structures defined at the atomic level require to be modeled through atomistic approaches. From a computational point of view, the latter approaches are generally associated with high computational costs, which have substantially hampered their extensive use. In this work, we report on a computationally fast formulation of a classical, fully atomistic approach, able to accurately describe both metal nanoparticles and graphene-like nanostructures composed of roughly 1 million atoms and characterized by structural defects.

A General Route to Include Pauli Repulsion and Quantum Dispersion Effects in QM/MM Approaches.

A methodology to account for nonelectrostatic interactions in Quantum Mechanical (QM)/Molecular Mechanics (MM) approaches is developed. Formulations for Pauli repulsion and dispersion energy, explicitly depending on the QM density, are derived. Such expressions are based on the definition of an auxiliary density on the MM portion and the Tkatchenko-Scheffler (TS) approach, respectively. The developed method is general enough to be applied to any QM/MM method and partition, provided an accurate tuning of a small number of parameters is obtained. The coupling of the method with both nonpolarizable and fully polarizable QM/fluctuating charge (FQ) approaches is reported and applied. A suitable parametrization for the aqueous solution, so that its most representative features are well reproduced, is outlined. Then, the obtained parametrization and method are applied to calculate the nonelectrostatic (repulsion and dispersion) interaction energy of nicotine in aqueous solution.