Harmonic and anharmonic vibrational computations for biomolecular building blocks: Benchmarking DFT and basis sets by theoretical and experimental IR spectrum of glycine conformers.

Advanced vibrational spectroscopic experiments have reached a level of sophistication that can only be matched by numerical simulations in order to provide an unequivocal analysis, a crucial step to understand the structure-function relationship of biomolecules. While density functional theory (DFT) has become the standard method when targeting medium-size or larger systems, the problem of its reliability and accuracy are well-known and have been abundantly documented. To establish a reliable computational protocol, especially when accuracy is critical, a tailored benchmark is usually required. This is generally done over a short list of known candidates, with the basis set often fixed a priori. In this work, we present a systematic study of the performance of DFT-based hybrid and double-hybrid functionals in the prediction of vibrational energies and infrared intensities at the harmonic level and beyond, considering anharmonic effects through vibrational perturbation theory at the second order. The study is performed for the six-lowest energy glycine conformers, utilizing available "state-of-the-art" accurate theoretical and experimental data as reference. Focusing on the most intense fundamental vibrations in the mid-infrared range of glycine conformers, the role of the basis sets is also investigated considering the balance between computational cost and accuracy. Targeting larger systems, a broad range of hybrid schemes with different computational costs is also tested.

CPL of Mellein and Related Natural Compounds: Analysis of the ESIPT Phenomenon.

(R)-(-)-Mellein, (3R,4R)-4-hydroxymellein and (3R,4S)-4-hydroxymellein obtained from fungi, i.e. from Diplodia globulosa, were investigated as a class of natural products presenting ESIPT (excited state intramolecular proton transfer) phenomenon, through fluorescence and CPL (circularly polarized luminescence). The study was preceded by the assessment of the absolute configuration through ECD and VCD (electronic and vibrational circular dichroism) spectroscopies in addition to NMR spectra. It is found that ESIPT takes place in these systems very rapidly, and no dual fluorescence has been observed. The experimental study is backed up by TD-DFT calculations of ECD and CPL spectra, plus MD dynamics to follow proton transfer in the excited state and careful analysis of the puckering dynamics of the lactone ring. Deprotonated forms of the three compounds were also investigated by the same chiroptical experimental and theoretical methods, showing how one can find in natural compounds not only biological activity but also biologically compatible sensing probes.

Mid-IR and CH stretching vibrational circular dichroism spectroscopy to distinguish various sources of chirality: The case of quinophaneoxazoline based ruthenium(II) complexes.

Five diastereomers of ruthenium(II) complexes based on quinolinophaneoxazoline ligands were investigated by vibrational circular dichroism (VCD) in the mid-IR and CH stretching regions. Diastereomers differ in three sources of chirality: the planar chirality of the quinolinophane moiety, the central chirality of an asymmetric carbon atom of the oxazoline ring, and the chirality of the ruthenium atom. VCD, allied to DFT calculations, has been found to be effective in disentangling the various forms of chirality. In particular, a VCD band is identified in the CH stretching region directly connected to the chirality of the metal. The analysis of the calculated VCD spectra is carried out by partitioning the complexes into fragments. The anharmonic analysis is also performed with a recently proposed reduced-dimensionality approach: such treatment is particularly important when examining spectroscopic regions highly perturbed by resonances, like the CH stretching region.

Matrix-isolation and cryosolution-VCD spectra of α-pinene as benchmark for anharmonic vibrational spectra calculations.

The inclusion of anharmonicity in vibrational spectral analyis remains associated to small molecular systems with up to a dozen of atoms, with half a dozen of non-hydrogen atoms, typically thesize of propylene oxide. One may see two reasons for this: first of all, larger systems are often thought to be computationally too demanding (high computational costs) for a full anharmonic vibrational analysis. Second, the identification of resonances and their correction is often considered something only expert theoreticians could address because of the lack of unequivocal criteria. In this contribution, we illustrate that resonances can indeed become a complex problem, which can be handled almost transparently thanks to recent advances in vibrational perturbation theory (VPT2). The study also emphasizes the importance and the central role played by experiment in benchmarking novel theoretical approaches. In fact, we herein provide the currently highest resolution VCD spectra available for α- and ß-pinene obtained under matrix-isolation conditions and in liquid Xenon as solvent. They are interpreted by VPT2 with novel tests for the identification of resonances. Hence, the study demonstrates the mutual stimulation of advances in both experimental techniques and computational models.

Combination of Resonance and Non-Resonance Chiral Raman Scattering in a Cobalt(III) Complex.

Resonance Raman optical activity (RROA) spectra with high sensitivity reveal details on molecular structure, chirality, and excited electronic properties. Despite the difficulty of the measurements, the recorded data for the Co(III) complex with S,S-N,N-ethylenediaminedisuccinic acid are of exceptional quality and, coupled with the theory, spectacularly document the molecular behavior in resonance. This includes a huge enhancement of the chiral scattering, contribution of the antisymmetric polarizabilities to the signal, and the Herzberg-Teller effect significantly shaping the spectra. The chiral component is by about one order of magnitude bigger than for an analogous aluminum complex. The band assignment and intensity profile were confirmed by simulations based on density functional and vibronic theories. The resonance was attributed to the S0 →S3 transition, with the strongest signal enhancement of Raman and ROA spectral bands below about 800 cm-1 . For higher wavenumbers, other excited electronic states contribute to the scattering in a less resonant way. RROA spectroscopy thus appears as a unique tool to study the structure and electronic states of absorbing molecules in analytical chemistry, biology, and material science.

Modulation of π character upon complexation captured by molecular rotation spectra.

Two configurations of the furan-CF3Cl complex have been observed by high-resolution rotational spectroscopy. One is characterized by a dominant Cl lone pair⋯π*aromatic interaction and the other is stabilized by a C-Cl···π-CC- halogen bond. This is the first rotational spectroscopic evidence, to the best of our knowledge, that shows how a complexation with a partner like CF3Cl (the weak lone pair belt of Cl, to be more specific) can modulate both the aromatic π* and diene π characters of a heteroaromatic molecule in the formation of non-covalent interactions. The results emphasize the partner molecules' role in modulating the π electron structure and will not only deepen our understanding on non-covalent interactions but also lead to better designs of heteroaromatic-based drugs and materials.

Accounting for molecular flexibility in photoionization: case of tert-butyl hydroperoxide.

tert-Butyl hydroperoxide (tBuOOH) is a common intermediate in the oxidation of organic compounds that needs to be accurately quantified in complex gas mixtures for the development of chemical kinetic models of low temperature combustion. This work presents a combined theoretical and experimental investigation on the synchrotron-based VUV single photon ionization of gas-phase tBuOOH in the 9.0 - 11.0 eV energy range, including dissociative ionization processes. Computations consist of the determination of the structures, vibrational frequencies and the energetics of neutral and ionic tBuOOH. The Franck-Condon spectrum for the tBuOOH+ (X+) + e- ← tBuOOH (X) + hν transition is computed, where special treatment is undertaken because of the flexibility of tBuOOH, in particular regarding the OOH group. Through comparison of the experimental mass-selected threshold photoelectron spectra with explicitly correlated coupled cluster calculations and Franck-Condon simulations that account for the flexibility of the molecule, an estimation of the ionization energy is given. The appearance energy of the only fragment observed within the above-mentioned energy range, identified as the tert-butyl C4H9+, is also reported. Finally, the signal branching ratio between the parent and the fragment ions is provided as a function of photon energy, essential to quantify tBuOOH in gas-phase oxidation/combustion experiments via advanced mass spectrometry techniques.

An Effective and Automated Processing of Resonances in Vibrational Perturbation Theory Applied to Spectroscopy.

The broader availability of cost-effective methodologies like second-order vibrational perturbational theory (VPT2), also in general-purpose quantum chemical programs, has made the inclusion of anharmonic effects in vibrational calculations easier, paving the way to more accurate simulations. Combined with modern computing hardware, VPT2 can be used on relatively complex molecular systems with dozen of atoms. However, the problem of resonances and their corrections remains a critical pitfall of perturbative methods. Recent works have highlighted the sensitivity of band intensities to even subtle resonance effects, underlying the importance of a correct treatment to predict accurate spectral bandshapes. This aspect is even more critical with chiroptical spectroscopies whose signal is weak. This has motivated the present work in exploring robust methods and criteria to identify resonances not only in energy calculations but also on the transition moments. To study their performance, three molecules of representative sizes ranging from ten to several dozens of atoms were chosen. The impact of resonances, as well as the accuracy achievable once they are properly treated, is illustrated by the changes in spectral bandshapes, including chiroptical spectroscopies.

Accurate Quantum Chemical Spectroscopic Characterization of Glycolic Acid: A Route Toward its Astrophysical Detection.

The first step to shed light on the abiotic synthesis of biochemical building blocks, and their further evolution toward biological systems, is the detection of the relevant species in astronomical environments, including earthlike planets. To this end, the species of interest need to be accurately characterized from structural, energetic, and spectroscopic viewpoints. This task is particularly challenging when dealing with flexible systems, whose spectroscopic signature is ruled by the interplay of small- and large-amplitude motions (SAMs and LAMs, respectively) and is further tuned by the conformational equilibrium. In such instances, quantum chemical (QC) calculations represent an invaluable tool for assisting the interpretation of laboratory measurements or even observations. In the present work, the role of QC results is illustrated with reference to glycolic acid (CH2OHCOOH), a molecule involved in photosynthesis and plant respiration and a precursor of oxalate in humans, which has been detected in the Murchison meteorite but not yet in the interstellar medium or in planetary atmospheres. In particular, the equilibrium structure of the lowest-energy conformer is derived by employing the so-called semiexperimental approach. Then, accurate yet cost-effective QC calculations relying on composite post-Hartree-Fock schemes and hybrid coupled-cluster/density functional theory approaches are used to predict the structural and ro-vibrational spectroscopic properties of the different conformers within the framework of the second-order vibrational perturbation theory. A purposely tailored discrete variable representation anharmonic approach is used to treat the LAMs related to internal rotations. The computed spectroscopic data, particularly those in the infrared region, complement the available experimental investigations, thus enhancing the possibility of an astronomical detection of this molecule.

Anharmonic Aspects in Vibrational Circular Dichroism Spectra from 900 to 9000 cm-1 for Methyloxirane and Methylthiirane.

Vibrational circular dichroism (VCD) spectra and the corresponding IR spectra of the chiral isomers of methyloxirane and of methylthiirane have been reinvestigated, both experimentally and theoretically, with particular attention to accounting for anharmonic corrections, as calculated by the GVPT2 approach. De novo recorded VCD spectra in the near IR (NIR) range regarding CH-stretching overtone transitions, together with the corresponding NIR absorption spectra, were also considered and accounted for, both with the GVPT2 and with the local mode approaches. Comparison of the two methods has permitted us to better describe the nature of active "anharmonic" modes in the two molecules and the role of mechanical and electrical anharmonicity in determining the intensities of VCD and IR/NIR data. Finally, two nonstandard IR/NIR regions have been investigated: the first one about ≈2000 cm-1, involving mostly two-quanta bending mode transitions, the second one between 7000 and 7500 cm-1 involving three-quanta transitions containing CH-stretching overtones and HCC/HCH bending modes.

Accuracy and Interpretability: The Devil and the Holy Grail. New Routes across Old Boundaries in Computational Spectroscopy.

The past decade has witnessed an increasing interaction between experiment and theory in the field of molecular spectroscopy. On the computational side, ongoing developments of hardware and software have moved computational spectroscopy from a highly specialized research area to a general tool for researchers in different fields of chemical science. However, since its dawn, computational spectroscopy has been characterized by the dichotomies of qualitative and quantitative description, and of interpretation and accuracy. Indeed, the analysis of experiments is seldom straightforward because of the subtle interplay of several different effects, which are not easy to evaluate and isolate, and/or the complexity of the system under consideration. Often, the accuracy has to be set aside for a more qualitative analysis that will provide the means for a broad interpretation. In such a scenario, the most recent advances in theoretical treatments as well as computational tools have opened the way to the reconciliation of accuracy and interpretability, resulting in unequivocal analyses and assignments of experimental spectra and their unbiased interpretation. This Review aims at being a comprehensive, authoritative, critical, and readable account of general interest to the chemistry community because of the wealth of qualitative and quantitative information that can be obtained from spectroscopic investigations. Limiting ourselves to rotational and vibrational spectroscopy, emphasis will be put on accuracy and interpretability as well as on the routes toward their reconciliation and integration.

Unusual binary aggregates of perylene bisimide revealed by their electronic transitions in helium nanodroplets and DFT calculations.

The S1 ← S0 electronic transition of perylene bisimide (PBI) and its binary aggregates were investigated using a combination of helium nanodroplet isolation spectroscopy and computational methods. First, well-resolved vibronic bands of the PBI monomer obtained under the superfluid helium nanodroplet environment were compared to simulated vibronic spectra with anharmonic corrections of the band positions. Second, about ten sets of weaker vibronic bands were observed, which show similar vibronic patterns as that of the PBI monomer and have their band origins red-shifted by about 8 to 218 cm-1. Experimental Poisson curve analyses, performed at the origins of these new sets of bands and the PBI monomer, indicate that the carriers of these weaker red-shifted vibronic bands are binary adducts of PBI. Three types of PBI dimer structures where the electronic transition dipole moments of the two subunits are perpendicular to each other were proposed as possible carriers of these red-shifted vibronic patterns. Extensive vibronic simulations were carried out in a multi-step procedure with TD-DFT, vertical Hessian, and finally adiabatic Hessian approaches. Small red-shifted band origins and very similar vibronic patterns to that of the monomer were predicted for unusual, T-shaped, type I dimer structures and are in close agreement with the experimental data. The combined experimental and theoretical results indicate that the helium nanodroplet environment enables the formation of these unusual T-shaped dimers and stabilizes them.

Unraveling the internal conversion process within the Q-bands of a chlorophyll-like-system through surface-hopping molecular dynamics simulations.

The non-radiative relaxation process within the Q-bands of chlorophylls represents a crucial preliminary step during the photosynthetic mechanism. Despite several experimental and theoretical efforts performed in order to clarify the complex dynamics characterizing this stage, a complete understanding of this mechanism is still far to be reached. In this study, non-adiabatic excited-state molecular dynamic simulations have been performed to model the non-radiative process within the Q-bands for a model system of chlorophylls. This system has been considered in the gas phase and then, to have a more representative picture of the environment, with implicit and mixed implicit-explicit solvation models. In the first part of this analysis, absorption spectra have been simulated for each model in order to guide the setup for the non-adiabatic excited-state molecular dynamic simulations. Then, non-adiabatic excited-state molecular dynamic simulations have been performed on a large set of independent trajectories and the population of the Qx and Qy states has been computed as the average of all the trajectories, estimating the rate constant for the process. Finally, with the aim of investigating the possible role played by the solvent in the Qx-Qy crossing mechanism, an essential dynamic analysis has been performed on the generated data, allowing one to find the most important motions during the simulated dynamics.

Role of specific solute-solvent interactions on the photophysical properties of distyryl substituted BODIPY derivatives.

Computational spectroscopy is now a valuable tool to better understand experimental spectroscopic data. Recent advancements in computational methods allow the study of electronic excited states of medium-large molecular systems with greater accuracy, simulating spectra directly comparable with experiments. Besides the system of interest, proper modelling of the environment effects is essential to reach a sufficient level of accuracy. This is especially important for solvents with high polarity or those able to establish specific interactions with the solute. One of the most straightforward and fastest ways to deal with solvent effects is the use of implicit models, like the polarizable continuum model (PCM). However, these models cannot describe specific solute-solvent interactions. In this case, one possible solution is the adoption of a mixed model that includes the solute and few solvent molecules within a PCM cavity. With the aim of investigating the role played by specific solute-solvent interactions, the behaviour of styryl substituted BODIPY systems in methanol has been studied at a theoretical level, considering both implicit and mixed implicit-explicit models. In the first part of our analysis, vibrationally resolved electronic spectra for absorption and emission processes have been simulated, using several sets of coordinates to represent normal modes, and compared with experiments. Then, to verify if specific solute-solvent interactions play a crucial role during the ultrafast intraband relaxation processes, 2D electronic spectra were also simulated, which could provide valuable information on the complex ultrafast dynamics.

Toward Fully Unsupervised Anharmonic Computations Complementing Experiment for Robust and Reliable Assignment and Interpretation of IR and VCD Spectra from Mid-IR to NIR: The Case of 2,3-Butanediol and trans-1,2-Cyclohexanediol.

The infrared (IR) and vibrational circular dichroism (VCD) spectra of 2,3-butanediol and trans-1,2-cyclohexanediol from 900 to 7500 cm-1 (including mid-IR, fundamental CH and OH stretchings, and near-infrared regions) have been investigated by a combined experimental and computational strategy. The computational approach is rooted in density functional theory (DFT) computations of harmonic and leading anharmonic mechanical, electrical, and magnetic contributions, followed by a generalized second-order perturbative (GVPT2) evaluation of frequencies and intensities for all the above regions without introducing any ad hoc scaling factor. After proper characterization of large-amplitude motions, all resonances plaguing frequencies and intensities are taken into proper account. Comparison of experimental and simulated spectra allows unbiased assignment and interpretation of the most interesting features. The reliability of the GVPT2 approach for OH stretching fundamentals and overtones is confirmed by the remarkable agreement with a local mode model purposely tailored for the latter two regions. Together with the specific interest of the studied molecules, our results confirm that an unbiased assignment and interpretation of vibrational spectra for flexible medium-size molecules can be achieved by means of a nearly unsupervised reliable, robust, and user-friendly DFT/GVPT2 model.

Vibrational circular dichroism under the quantum magnifying glass: from the electronic flow to the spectroscopic observable.

We present a comprehensive methodology for the analysis and interpretation of vibrational circular dichroism spectra supported by novel graphical representations. The tools rely on the vibrational transition current density (VTCD) associated with a molecular vibration, whose visualization allows exploration of the physical origin of the electronic contribution to the electric and magnetic vibrational dipole transition moments. Different ways of visualizing VTCD from 2D maps to 3D representations are reported and applied to molecular systems of growing complexity. An extension of the VTCD analysis to fully anharmonic spectra within the second-order vibrational perturbation theory (VPT2) is discussed. The analysis is applied to different types of chiral systems: the doubly deuterated oxirane (2S,3S)-oxirane-d2, taken as a reference to validate our implementation; 1,3-difluoroallene, a simple rigid system to explore the application of VTCD to anharmonic VCD spectra. Finally, the analysis of VTCD has been used to better understand the origin of the signal enhancement in peptides linked to the ferrocene groups. The merits and shortcomings of the methods are discussed, and some perspectives for future developments are offered.

State-of-the-art computation of the rotational and IR spectra of the methyl-cyclopropyl cation: hints on its detection in space.

Recent measurements by the Cassini Ion Neutral Mass Spectrometer demonstrated the presence of numerous carbocations in Titan's upper atmosphere. In [Ali et al., Planet. Space Sci., 2013, 87, 96], an analysis of these measurements revealed the formation of the three-membered cyclopropenyl cation and its methyl derivatives. As a starting point of a future coordinated effort of laboratory experiments, quantum-chemical calculations, and astronomical observations, in the present work the molecular structure and spectroscopic properties of the methyl-cyclopropenyl cation have been investigated by means of state-of-the-art computational approaches in order to simulate its rotational and infrared spectra. Rotational parameters have been predicted with an expected accuracy better than 0.1% for rotational constants and on the order of 1-2% for centrifugal-distortion terms. As for the infrared spectrum, despite the challenge of a large amplitude motion, fundamental transitions have been computed to a good accuracy, i.e., the uncertainties are expected to be smaller than 5-10 wavenumbers.

On the simulation of vibrationally resolved electronic spectra of medium-size molecules: the case of styryl substituted BODIPYs.

BODIPY dyes are used in a variety of applications because of their peculiar spectroscopic and photo-physical properties that vary depending on the stereochemistry of the functional groups attached to the boron-dipyrromethene core structure. In this work, we have applied several computational methods, adapted for semi-rigid molecules based on the Franck-Condon principle, for the study of the optical properties of BODIPY systems and for the understanding of the influence of functional groups on their spectroscopic features. We have analyzed the electronic spectra of two styryl substituted BODIPY molecules of technological interest, properly taking into account the vibronic contribution. For comparison with recently recorded experimental data in methanol, the vibrationally resolved electronic spectra of these systems were computed using both Time-Independent (TI) and Time-Dependent (TD) formalisms. The first step toward the analysis of optical properties of the styryl modified BODIPYs was a benchmark of several density functionals, to select the most appropriate one. We have found that all benchmarked functionals provide good results in terms of band shape but some of them show strong discrepancies in terms of band position. Beyond the issue of the electronic structure calculation method, different levels of sophistication can be adopted for the calculation of vibronic transitions. In this study, the effect of mode couplings and the influence of the Herzberg-Teller terms on the theoretical spectra has been investigated. It has been found that all levels of theory considered give reproducible results for the investigated systems: band positions and shapes are similar at all levels and little improvements have been found in terms of band shape with the inclusion of Herzberg-Teller effect. Inclusion of temperature effects proved to be challenging due to the important impact of large amplitude motions. Better agreement can be achieved by adopting a suitable set of coordinates coupled with a reduced-dimensionality scheme.

The vibrational CD spectra of propylene oxide in liquid xenon: a proof-of-principle CryoVCD study that challenges theory.

Propylene oxide (PO) is one of the smallest chiral molecules and thus the ideal candidate to benchmark both new experimental and theoretical approaches. Previous studies on the fingerprint region of the IR and VCD spectra of PO under matrix-isolation conditions revealed a good performance of theoretical approaches to reproduce anharmonic frequencies and intensities. For certain bands which were found to be involved in Fermi resonances, theory did not agree with the experimental observations. Herein we present the IR and VCD spectra of PO recorded in liquefied xenon, an experimental environment which combines the advantages of solution phase and matrix environment. This unique environment allows us to record well-resolved VCD signatures of many combination modes. We show that the VCD signatures of the Fermi resonant modes previously reported for MI-VCD conditions are likely to arise due to matrix effects. Therefore, we compare the experimental results obtained in liquid xenon with state-of-the-art anharmonic spectra calculations in order to shed more light on the assignments of the IR and VCD spectral signatures of PO.

Ferrocenes with simple chiral substituents: an in-depth theoretical and experimental VCD and ECD study.

Circular dichroism spectra in the IR range (VCD = vibrational circular dichroism) and in the UV range (ECD = electronic circular dichroism) have been recorded for both enantiomers of simple mono-substituted ferrocenes containing chiral pendants: 1-acetoxyethylferrocene, 1, 1-methoxyethylferrocene, 2, and 1-hydroxyethylferrocene, 3; the related disubstituted 1,1'-bis(1-hydroxyethyl)ferrocene, 4, was also considered. These two types of spectra, with the support of DFT calculations, concur to unequivocally confirm the absolute configuration for 1-4. In particular, our computational results point out the clear advantage of using an anharmonic oscillator model for the interpretation of VCD spectra of chiral ferrocenes. Interesting conformational properties are either confirmed or established by the technique, like the eclipsed conformation of the two cyclopentadienyl rings and an intra-molecular interaction involving the OH for 3. For 4, NMR, VCD and IR spectra are compatible with dimer formation and in this case a distorted conformation is predicted. Of utmost importance for the absolute configuration assignment in mono-substituted ferrocenes, we were able to identify a diagnostic VCD band at 950 cm-1 and a (low intensity) ECD band that clearly indicate the absolute configuration of the whole series.