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A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.

The projected complex absorbing potential (CAP) technique is one of the methods that allow one to extend the bound state methods for computing resonances' energies and widths. Here, we explore the accuracy of the potential energy curves generated with different electronic structure theory methods in combination with the projected CAP technique by considering resonant vibrational excitation (RVE) of N2 by electron impact as a model process. We report RVE cross sections computed using the boomerang model with potential energy curves obtained with CAP-based extended multistate complete active space perturbation theory (XMS-CASPT2) and equation of motion coupled-cluster method for electron attachment with single and double substitution (EOM-EA-CCSD) methods. We also compare potential energy curves computed with several electronic structure methods, including XMS-CASPT2, EOM-EA-CCSD, multireference configuration interaction with singles (MR-CIS) and singles and doubles (MR-CISD). A good agreement is observed between the experiment and simulated RVE cross sections obtained with the potential energy curves generated with XMS-CASPT2 and EOM-EA-CCSD methods, thus highlighting the potential of the projected CAP technique combined with accurate electronic structure methods for dynamical simulations of the processes that proceed through metastable electronic states., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The complex absorbing potential (CAP) approach offers a practical tool for characterization of energies and lifetimes of metastable electronic states, such as temporary anions and core ionized states. Here, we present an implementation of the smooth Voronoi CAP combined with the equation-of-motion coupled cluster with single and double substitutions method for metastable states. The performances of the smooth Voronoi CAP and box CAP are compared for different classes of systems: resonances in isolated molecules and localized and delocalized resonances in molecular clusters. The benchmark calculations show that the Voronoi CAP is generally more robust when applied to molecular clusters, but box CAPs are equally reliable for localized resonances or in the cases when the resonance does not exhibit significant electron density delocalization into the intramolecular region. As such, the choice of the CAP shape and onset should be guided by the character of the metastable states.

The complex absorbing potential equation-of-motion coupled-cluster (CAP-EOM-CC) method is routinely used to investigate metastable electronic states in small molecules. However, the requirement of evaluating eigenvalue trajectories presents a barrier to larger simulations, as each point corresponding to a different value of the CAP strength parameter requires a unique eigenvalue calculation. Here, we present a new implementation of CAP-EOM-CCSD that uses a subspace projection scheme to evaluate resonance positions and widths at the overall cost of a single electronic structure calculation. We analyze the performance of the projected CAP-EOM-CC scheme against the conventional scheme, where the CAP is incorporated starting from the Hartree-Fock level, for various small and medium sized molecules, and investigate its sensitivity to various parameters. Finally, we report resonance parameters for a set of molecules commonly used for benchmarking CAP-based methods, and we report estimates of resonance energies and widths for 1- and 2-cyanonaphtalene, molecules that were recently detected in the interstellar medium.

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.

Redox reactions are crucial to biological processes that protect organisms against oxidative stress. Metalloenzymes, such as peroxidases which reduce excess reactive oxygen species into water, play a key role in detoxification mechanisms. Here we present the results of a polarizable QM/MM study of the reduction potential of the electron transfer heme in the cytochrome c peroxidase of Nitrosomonas europaea. We have found that environment polarization does not substantially affect the computed value of the redox potential. Particular attention has been given to analyzing the role of electrostatic interactions within the protein environment and the solvent on tuning the redox potential of the heme co-factor. We have found that the electrostatic interactions predominantly explain the fluctuations of the vertical ionization/attachment energies of the heme for the sampled configurations, and that the long range electrostatic interactions (up to 40 Å) contribute substantially to the absolute values of the vertical energy gaps.

An accurate but efficient description of noncovalent interactions is a key to predictive modeling of biological and materials systems. The effective fragment potential (EFP) is an ab initio -based force field that provides a physically meaningful decomposition of noncovalent interactions of a molecular system into Coulomb, polarization, dispersion, and exchange-repulsion components. An EFP simulation protocol consists of two steps, preparing parameters for molecular fragments by a series of ab initio calculations on each individual fragment, and calculation of interaction energy and properties of a total molecular system based on the prepared parameters. As the fragment parameters (distributed multipoles, polarizabilities, localized wave function, etc. ) depend on a fragment geometry, straightforward application of the EFP method requires recomputing parameters of each fragment if its geometry changes, for example, during thermal fluctuations of a molecular system. Thus, recomputing fragment parameters can easily become both computational and human bottlenecks and lead to a loss of efficiency of a simulation protocol. An alternative approach, in which fragment parameters are adjusted to different fragment geometries, referred to as "flexible EFP", is explored here. The parameter adjustment is based on translations and rotations of local coordinate frames associated with fragment atoms. The protocol is validated on extensive benchmark of amino acid dimers extracted from molecular dynamics snapshots of a cryptochrome protein. A parameter database for standard amino acids is developed to automate flexible EFP simulations in proteins. To demonstrate applicability of flexible EFP in large-scale protein simulations, binding energies and vertical electron ionization and electron attachment energies of a lumiflavin chromophore of the cryptochrome protein are computed. The results obtained with flexible EFP are in a close agreement with the standard EFP procedure but provide a significant reduction in computational cost.

eMap is a web-based platform for identifying and visualizing electron or hole transfer pathways in proteins based on their crystal structures. The underlying model can be viewed as a coarse-grained version of the Pathways model, where each tunneling step between hopping sites represented by electron transfer active (ETA) moieties is described with one effective decay parameter that describes protein-mediated tunneling. ETA moieties include aromatic amino acid residue side chains and aromatic fragments of cofactors that are automatically detected, and, in addition, electron/hole residing sites that can be specified by the users. The software searches for the shortest paths connecting the user-specified electron/hole source to either all surface-exposed ETA residues or the user-specified target. The identified pathways are ranked according to their effective length. The pathways are visualized in 2D as a graph, in which each node represents an ETA site, and in 3D using available protein visualization tools. Here, we present the capability and user interface of eMap 1.0, which is available at https://emap.bu.edu .

Redox reactions play a key role in various biological processes, including photosynthesis and respiration. Quantitative and predictive computational characterization of redox events is therefore highly desirable for enriching our knowledge on mechanistic features of biological redox-active macromolecules. Here, we present a computational protocol exploiting polarizable embedding hybrid quantum-classical approach and resulting in accurate estimates of redox potentials of biological macromolecules. A special attention is paid to fundamental aspects of the theoretical description such as the effects of environment polarization and of the long-range electrostatic interactions on the computed energetic parameters. Environment (protein and the solvent) polarization is shown to be crucial for accurate estimates of the redox potential: hybrid quantum-classical results with and without account for environment polarization differ by 1.4 V. Long-range electrostatic interactions are shown to contribute significantly to the computed redox potential value even at the distances far beyond the protein outer surface. The approach is tested on simulating reduction potential of cryptochrome 1 protein from Arabidopsis thaliana. The theoretical estimate (0.07 V) of the midpoint reduction potential is in good agreement with available experimental data (-0.15 V).

Dissociative electron attachment (DEA) plays a key role in radiation damage of biomolecules under high-energy radiation conditions. The initial step in DEA is often rationalized in terms of resonant electron capture into one of the metastable valence states of a molecule followed by its fragmentation. Our combined theoretical and experimental investigations indicate that the manifold of states responsible for electron capture in the DEA process can be dominated by core-excited (shake-up) dipole-supported resonances. Specifically, we present the results of experimental and computational studies of the gas-phase DEA to three prototypical peptide molecules, formamide, N-methylformamide (NMF), and N,N-dimethyl-formamide (DMF). In contrast to the case of electron capture by positively charged peptides in which amide bond rupture is rare compared to N─C_{α} bond cleavage, fragmentation of the amide bond was observed in each of these three molecules. The ion yield curves for ions resulting from this amide bond cleavage, such as NH_{2}^{-} for formamide, NHCH_{3}^{-} for NMF, and N(CH_{3})_{2}^{-} for DMF, showed a double-peak structure in the region between 5 and 8 eV. The peaks are assigned to Feshbach resonances including core-excited dipole-supported resonances populated upon electron attachment based on high-level electronic structure calculations. Moreover, the lower energy peak is attributed to formation of the core-excited resonance that correlates with the triplet state of the neutral molecule. The latter process highlights the role of optically spin-forbidden transitions promoted by electron impact in the DEA process.

There have been numerous efforts, both experimental and theoretical, that have attempted to parametrize model Hamiltonians to describe excited state energy transfer in photosynthetic light harvesting systems. The Frenkel exciton model, with its set of electronically coupled two level chromophores that are each linearly coupled to dissipative baths of harmonic oscillators, has become the workhorse of this field. The challenges to parametrizing such Hamiltonians have been their uniqueness, and physical interpretation. Here we present a computational approach that uses accurate first-principles electronic structure methods to compute unique model parameters for a collection of local minima that are sampled with molecular dynamics and QM geometry optimization enabling the construction of an ensemble of local models that captures fluctuations as these systems move between local basins of inherent structure. The accuracy, robustness, and reliability of the approach is demonstrated in an application to the phycobiliprotein light harvesting complexes from cryptophyte algae. Our computed Hamiltonian ensemble provides a first-principles description of inhomogeneous broadening processes, and a standard approximate non-Markovian reduced density matrix dynamics description is used to estimate lifetime broadening contributions to the spectral line shape arising from electronic-vibrational coupling. Despite the overbroadening arising from this approximate line shape theory, we demonstrate that our model Hamiltonian ensemble approach is able to provide a reliable fully first-principles method for computation of spectra and can distinguish the influence of different chromophore protonation states in experimental results. A key feature in the dynamics of these systems is the excitation of intrachromophore vibrations upon electronic excitation and energy transfer. We demonstrate that the Hamiltonian ensemble approach provides a reliable first-principles description of these contributions that have been detailed in recent broad-band pump-probe and two-dimensional electronic spectroscopy experiments.

Electronic resonances are metastable states with finite lifetime embedded in the ionization or detachment continuum. They are ubiquitous in chemistry, physics, and biology. Resonances play a central role in processes as diverse as DNA radiolysis, plasmonic catalysis, and attosecond spectroscopy. This review describes novel equation-of-motion coupled-cluster (EOM-CC) methods designed to treat resonances and bound states on an equal footing. Built on complex-variable techniques such as complex scaling and complex absorbing potentials that allow resonances to be associated with a single eigenstate of the molecular Hamiltonian rather than several continuum eigenstates, these methods extend electronic-structure tools developed for bound states to electronic resonances. Selected examples emphasize the formal advantages as well as the numerical accuracy of EOM-CC in the treatment of electronic resonances. Connections to experimental observables such as spectra and cross sections, as well as practical aspects of implementing complex-valued approaches, are also discussed.

Photoinduced reactions play an important role in the photocycle of fluorescent proteins from the green fluorescent protein (GFP) family. Among such processes are photoisomerization, photooxidation/photoreduction, breaking and making of covalent bonds, and excited-state proton transfer (ESPT). Many of these transformations are initiated by electron transfer (ET). The quantum yields of these processes vary significantly, from nearly 1 for ESPT to 10 -4 -10 -6 for ET. Importantly, even when quantum yields are relatively small, at the conditions of repeated illumination the overall effect is significant. Depending on the task at hand, fluorescent protein photochemistry is regarded either as an asset facilitating new applications or as a nuisance leading to the loss of optical output. The phenomena arising due to phototransformations include (i) large Stokes shifts, (ii) photoconversions, photoactivation, and photoswitching, (iii) phototoxicity, (iv) blinking, (v) permanent bleaching, and (vi) formation of long-lived intermediates. The focus of this review is on the most recent experimental and theoretical work on photoinduced transformations in fluorescent proteins. We also provide an overview of the photophysics of fluorescent proteins, highlighting the interplay between photochemistry and other channels (fluorescence, radiationless relaxation, and intersystem crossing). The similarities and differences with photochemical processes in other biological systems and in dyes are also discussed.

Quantitative prediction of the energetics of redox half-reactions is still a challenge for modern computational chemistry. Here, we propose a simple scheme for reliable calculations of vertical ionization and attachment energies, as well as of redox potentials of solvated molecules. The approach exploits linear response approximation in the context of explicit solvent simulations with spherical boundary conditions. It is shown that both vertical ionization energies and vertical electron affinities, and, consequently redox potentials, exhibit linear dependence on the inverse radius of the solvation sphere. The explanation of the linear dependence is provided, and an extrapolation scheme is suggested. The proposed approach accounts for the specific short-range interactions within hybrid DFT and effective fragment potential approach as well as for the asymptotic system-size effects. The computed vertical ionization energies and redox potentials are in excellent agreement with the experimental values.

Photoinduced electron transfer in fluorescent proteins from the GFP family can be regarded either as an asset facilitating new applications or as a nuisance leading to the loss of optical output. Photooxidation commonly results in green-to-red photoconversion called oxidative redding. We discovered that yellow FPs do not undergo redding; however, the redding is restored upon halide binding. Calculations of the energetics of one-electron oxidation and possible electron transfer (ET) pathways suggested that excited-state ET proceeds through a hopping mechanism via Tyr145. In YFPs, the π-stacking of the chromophore with Tyr203 reduces its electron-donating ability, which can be restored by halide binding. Point mutations confirmed that Tyr145 is a key residue controlling ET. Substitution of Tyr145 by less-efficient electron acceptors resulted in highly photostable mutants. This strategy (i.e., calculation and disruption of ET pathways by mutations) may represent a new approach toward enhancing photostability of FPs.

Photoinduced dynamics of the para-benzoquinone anion features a subtle interplay between autodetachment and non-adiabatic transitions involving a dense manifold of resonances. We report the results of a multistate multireference perturbation theory study of the electronic structure of the para-benzoquinone anion in the ground, several low-lying excited electronic states, and in the lowest electron-detached state (the ground state of the neutral molecule). The electronic structure calculations revealed non-planar equilibrium geometry of the (2)Au excited state of the anion, but the effects of non-planarity on the shape of the absorption spectrum are found to be minor. Despite the large differences in the vertical excitation energies for the two lowest bright excited states, (2)Au (2.55 eV) and (2)B3u (2.93 eV), the simulated absorption spectra significantly overlap for the photon energies below 2.7 eV. Relevant minimum energy crossing points have been located using the CASSCF method. Excited-state deactivation channels are discussed in the context of accurate energetics and recent spectroscopic studies of the para-benzoquinone anion.

We present a combined computational and threshold photoelectron photoion coincidence study of two isotopologues of dimethyl ether, (DME - h6)n and (DME - d6)n n = 1 and 2, in the 9-14 eV photon energy range. Multiple isomers of neutral dimethyl ether dimer were considered, all of which may be present, and exhibited varying C-H⋯O interactions. Results from electronic structure calculations predict that all of them undergo barrierless proton transfer upon photoionization to the ground electronic state of the cation. In fact, all neutral isomers were found to relax to the same radical cation structure. The lowest energy dissociative photoionization channel of the dimer leads to CH3OHCH3 (+) by the loss of CH2OCH3 with a 0 K appearance energy of 9.71 ± 0.03 eV and 9.73 ± 0.03 eV for (DME - h6)2 and deuterated (DME - d6)2, respectively. The ground state threshold photoelectron spectrum band of the dimethyl ether dimer is broad and exhibits no vibrational structure. Dimerization results in a 350 meV decrease of the valence band appearance energy, a 140 meV decrease of the band maximum, thus an almost twofold increase in the ground state band width, compared with DME - d6 monomer.

Quinones are versatile biological electron acceptors and mobile electron carriers in redox processes. We present the first ab initio calculations of the width of the (2)A(u) shape resonance in the para-benzoquinone anion, the simplest member of the quinone family. This resonance state located at 2.5 eV above the ground state of the anion is believed to be a gateway state for electron attachment in redox processes involving quinones. We employ the equation-of-motion coupled-cluster method for electron affinity augmented by a complex-absorbing potential (CAP-EOM-EA-CCSD) to calculate the resonance position and width. The calculated width, 0.013 eV, is in excellent agreement with the width of the resonant peak in the photodetachment spectrum, thus supporting the assignment of the band to resonance excitation to the autodetaching (2)A(u) state. The methodological aspects of CAP-EOM-EA-CCSD calculations of resonances positions and widths in medium-sized molecules, such as basis set and CAP box size effects, are also discussed.

Kindling fluorescent protein (KFP), one of the chronologically first members of photoswitchable colored proteins from the green fluorescent protein (GFP) family, increasingly attracts efforts from experimental and theoretical sides. Ambiguous conclusions in solving puzzles of photochemistry of KFP and of its parent natural protein asFP595 are partially explained by lack of reliable theoretical data on chromophore properties in the electronically excited state. We report the results of state-of-the-art quantum chemistry calculations of the structure and energy of the KFP chromophore, 2-acetyl-,4-(p-hydroxybenzylidene)-1-methyl-5-imidazolone (AHBMI), both in the ground and excited states. Ground state equilibrium structures of anionic and zwitterionic protonation states of AHBMI were computed by the conventional MP2 method while excited state structures were characterized by the extended multireference perturbation theory method XMCQDPT2 including optimization of geometry parameters at this level. In particular, the computational results demonstrate that the basicity of the N2 nitrogen atom of the imidazolinone ring should noticeably increase upon electronic excitation, thus affecting excited state proton transfer events in proteins. The results of these simulations as well as of quantum mechanical-molecular mechanical (QM/MM) calculations for model protein systems evidence that KFP conformations with the zwitterionic chromophore are hardly expected to occur in the ground state, but may be populated upon excitation.

A production-level implementation of equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) for electron attachment and excitation energies augmented by a complex absorbing potential (CAP) is presented. The new method enables the treatment of metastable states within the EOM-CC formalism in a similar manner as bound states. The numeric performance of the method and the sensitivity of resonance positions and lifetimes to the CAP parameters and the choice of one-electron basis set are investigated. A protocol for studying molecular shape resonances based on the use of standard basis sets and a universal criterion for choosing the CAP parameters are presented. Our results for a variety of π(*) shape resonances of small to medium-size molecules demonstrate that CAP-augmented EOM-CCSD is competitive relative to other theoretical approaches for the treatment of resonances and is often able to reproduce experimental results.

Red fluorescent proteins (RFPs) are indispensable tools for deep-tissue imaging, fluorescence resonance energy transfer applications, and super-resolution microscopy. Using time-resolved optical spectroscopy this study investigated photoinduced dynamics of three RFPs, KillerRed, mRFP, and DsRed. In all three RFPs, a new transient absorption intermediate was observed, which decays on a microsecond-millisecond time scale. This intermediate is characterized by red-shifted absorption at 1.68-1.72 eV (λmax = 720-740 nm). On the basis of electronic structure calculations, experimental evidence, and published literature, the chemical nature of the intermediate is assigned to an unusual open-shell dianionic chromophore (dianion-radical) formed via photoreduction. A doubly charged state that is not stable in the isolated (gas phase) chromophore is stabilized by the electrostatic field of the protein. Mechanistic implications for photobleaching, blinking, and phototoxicity are discussed.

A new strategy of using complex absorbing potentials (CAPs) within electronic structure calculations of metastable electronic states, which are ubiquitous in chemistry and physics, is presented. The stumbling block in numerical applications of CAPs is the necessity to optimize the CAP strength for each system, state, and one-electron basis set, while there is no clear metric to assess the quality of the results and no simple algorithm of achieving numerical convergence. By analyzing the behavior of resonance wave functions, we found that robust results can be obtained when considering fully stabilized resonance states characterized by constant density at large η (parameter determining the CAP strength). Then the perturbation due to the finite-strength CAP can be removed by a simple energy correction derived from energy decomposition analysis and response theory. The utility of this approach is illustrated by CAP-augmented calculations of several shape resonances using EOM-EA-CCSD with standard Gaussian basis sets.

Motivated by the discrepancies in recent experimental and theoretical studies of photodetachment from isolated model chromophores of the green fluorescent protein (GFP), this study reports calculations of the electron detachment energies and photoelectron spectra of the phenolate and deprotonated p-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI) anions. The spectra were computed using double-harmonic parallel normal mode approximation. High-level coupled-cluster methods as well as density functional theory were used to compute vertical and adiabatic detachment energies of the phenolate anion serving as a model system representing anionic GFP-like chromophores (HBDI). The benchmark calculations reveal that the basis set has significant effect on the computed detachment energies, whereas the results are less sensitive to the level of electron correlation treatment. At least aug-cc-pVTZ basis set is required. The best ωB97X-D and CCSD(T) estimates of phenolate's adiabatic detachment energy are 2.12 and 2.19 eV; these values are very close to the experimental value, 2.253 eV [Gunion et al. Int. J. Mass Spectrom. Ion Proc. 1992, 117, 601]. The best estimate of the vertical detachment energy of deprotonated HBDI is 2.76 eV, which supports bound character of the bright excited state in the Franck-Condon region. The most intense transition in the computed photoelectron spectra of both phenolate and deprotonated HBDI is the 0-0 S0-D0 transition, which is 0.11 eV below vertical detachment energy. Therefore, the position of the maximum of the photoelectron spectrum does not represent vertical detachment energy, and the direct comparison between theory and experiment must involve spectrum modeling.

Water plays a central role in chemistry and biology by mediating the interactions between molecules, altering energy levels of solvated species, modifying potential energy profiles along reaction coordinates, and facilitating efficient proton transport through ion channels and interfaces. This study investigates proton transfer in a model system comprising dry and microhydrated clusters of nucleobases. With mass spectrometry and tunable vacuum ultraviolet synchrotron radiation, we show that water shuts down ionization-induced proton transfer between nucleobases, which is very efficient in dry clusters. Instead, a new pathway opens up in which protonated nucleobases are generated by proton transfer from the ionized water molecule and elimination of a hydroxyl radical. Electronic structure calculations reveal that the shape of the potential energy profile along the proton transfer coordinate depends strongly on the character of the molecular orbital from which the electron is removed; i.e., the proton transfer from water to nucleobases is barrierless when an ionized state localized on water is accessed. The computed energetics of proton transfer is in excellent agreement with the experimental appearance energies. Possible adiabatic passage on the ground electronic state of the ionized system, though energetically accessible at lower energies, is not efficient. Thus, proton transfer is controlled electronically, by the character of the ionized state, rather than statistically, by simple energy considerations.

Theory and implementation of complex-scaled variant of equation-of-motion coupled-cluster method for excitation energies with single and double substitutions (EOM-EE-CCSD) is presented. The complex-scaling formalism extends the EOM-EE-CCSD model to resonance states, i.e., excited states that are metastable with respect to electron ejection. The method is applied to Feshbach resonances in atomic systems (He, H(-), and Be). The dependence of the results on one-electron basis set is quantified and analyzed. Energy decomposition and wave function analysis reveal that the origin of the dependence is in electron correlation, which is essential for the lifetime of Feshbach resonances. It is found that one-electron basis should be sufficiently flexible to describe radial and angular electron correlation in a balanced fashion and at different values of the scaling parameter, θ. Standard basis sets that are optimized for not-complex-scaled calculations (θ = 0) are not sufficiently flexible to describe the θ-dependence of the wave functions even when heavily augmented by additional sets.

Benchmark calculations of the lowest ionized state of the (A:T)2 (mixed adenine-thymine) cluster at the geometry taken from the DNA X-ray structure are presented. Vertical ionization energies (IEs) computed by the equation-of-motion coupled-cluster method with single and double substitutions are reported and analyzed. The shift in IE relative to the monomer (A) is -0.7 eV. The performance of the widely used B3LYP, ωB97X-D, and M06-2X functionals with respect to their ability to describe energetics and the character (localization versus delocalization) of the ionized states is also investigated. The shifts in IEs caused by H-bonding and stacking interactions are analyzed in terms of additive versus cooperative effects. It is found that the cooperative effect accounts for more than 20% of the shift in IE relative to the monomer. The cooperative effect and, consequently, the magnitude of the shift are well reproduced by the hybrid quantum mechanics/molecular mechanics scheme in which neutral thymine bases are represented by point charges.

Irradiation of the green fluorescent protein (GFP) by intense violet or UV light leads to decarboxylation of the Glu222 side chain in the vicinity of the chromophore (Chro). This phenomenon is utilized in optical highlighters, such as photoactivatable GFP (PA-GFP). Using state-of-the-art quantum chemical calculations, we investigate the feasibility of the mechanism proposed in the experimental studies [van Thor et al. Nature Struct. Biol.2002, 9, 37-41; Bell et al. J. Am. Chem. Soc.2003, 125, 37-41]. It was hypothesized that a primary event of this photoconversion involves population of a charge-transfer (CT) state via either the first excited state S1 when using longer wavelength (404 and 476 nm) or a higher excited state when using higher energy radiation (254 and 280 nm). Based on the results of electronic structure calculations, we identify these critical CT states (produced by electron transfer from Glu to electronically excited Chro) and show that they are accessible via different routes, i.e., either directly, by one-photon absorption, or through a two-step excitation via S1. The calculations are performed for model systems representing the chromophore and the key nearby residues using two complementary approaches: (i) the multiconfigurational quasidegenerate perturbation theory of second order with the occupation restricted multiple active space scheme for configuration selection in the multiconfigurational self-consistent field reference; and (ii) the single-reference configuration interaction singles method with perturbative doubles that does not involve active space selection. We examined electronic transitions with nonzero oscillator strengths in the UV and visible range between the electronic states involving the Chro and Glu residues. Both methods predict the existence of CT states with nonzero oscillator strength in the UV range and a local excited state of the chromophore accessible via S1 that may lead to the target CT state. The results suggest several possible scenarios for the primary photoconversion event. We also demonstrate that the point mutation Thr203His exploited in PA-GFP results in shifting the light wavelength to access the CT up to 20 nm, which suggests a possibility of a rational design of photoactivatable proteins in silico.

Proton transfer is ubiquitous in chemistry and biology, occurring, for example, in proteins, enzyme reactions and across proton channels and pumps. However, it has always been described in the context of hydrogen-bonding networks ('proton wires') acting as proton conduits. Here, we report efficient intramolecular ionization-induced proton transfer across a 1,3-dimethyluracil dimer, a model π-stacked system with no hydrogen bonds. Upon photoionization by tunable vacuum ultraviolet synchrotron radiation, the dimethyluracil dimer undergoes proton transfer and dissociates to produce a protonated monomer. Deuterated dimethyluracil experiments confirm that proton transfer occurs from the methyl groups and not from the aromatic C-H sites. Calculations reveal qualitative differences between the proton transfer reaction coordinate in the π-stacked and hydrogen-bonded base pairs, and that proton transfer in methylated dimers involves significant rearrangements of the two fragments, facilitating a relatively low potential energy barrier of only 0.6 eV in the ionized dimer.

The unique properties of green fluorescent protein (GFP) have been harnessed in a variety of bioimaging techniques, revolutionizing many areas of the life sciences. Molecular-level understanding of the underlying photophysics provides an advantage in the design of new fluorescent proteins (FPs) with improved properties; however, because of its complexity, many aspects of the GFP photocycle remain unknown. In this Account, we discuss computational studies of FPs and their chromophores that provide qualitative insights into mechanistic details of their photocycle and the structural basis for their optical properties. In a reductionist framework, studies of well-defined model systems (such as isolated chromophores) help to understand their intrinsic properties, while calculations including protein matrix and/or solvent demonstrate, on the atomic level, how these properties are modulated by the environment. An interesting feature of several anionic FP chromophores in the gas phase is their low electron detachment energy. For example, the bright excited ππ* state of the model GFP chromophore (2.6 eV) lies above the electron detachment continuum (2.5 eV). Thus, the excited state is metastable with respect to electron detachment. This autoionizing character needs to be taken into account in interpreting gas-phase measurements and is very difficult to describe computationally. Solvation (and even microsolvation by a single water molecule) stabilizes the anionic states enough such that the resonance excited state becomes bound. However, even in stabilizing environments (such as protein or solution), the anionic chromophores have relatively low oxidation potentials and can act as light-induced electron donors. Protein appears to affect excitation energies very little (<0.1 eV), but alters ionization or electron detachment energies by several electron volts. Solvents (especially polar ones) have a pronounced effect on the chromophore's electronic states; for example, the absorption wavelength changes considerably, the ground-state barrier for cis-trans isomerization is reduced, and fluorescence quantum yield drops dramatically. Calculations reveal that these effects can be explained in terms of electrostatic interactions and polarization, as well as specific interactions such as hydrogen bonding. The availability of efficient computer implementations of predictive electronic structure methods is essential. Important challenges include developing faster codes (to enable better equilibrium sampling and excited-state dynamics modeling), creating algorithms for properties calculations (such as nonlinear optical properties), extending standard excited-state methods to autoionizing (resonance) states, and developing accurate QM/MM schemes. The results of sophisticated first-principle calculations can be interpreted in terms of simpler, qualitative molecular orbital models to explain general trends. In particular, an essential feature of the anionic GFP chromophore is an almost perfect resonance (mesomeric) interaction between two Lewis structures, giving rise to charge delocalization, bond-order scrambling, and, most importantly, allylic frontier molecular orbitals spanning the methine bridge. We demonstrate that a three-center Hückel-like model provides a useful framework for understanding properties of FPs. It can explain changes in absorption wavelength upon protonation or other structural modifications of the chromophore, the magnitude of transition dipole moment, barriers to isomerization, and even non-Condon effects in one- and two-photon absorption.

Understanding the chromophore maturation process in fluorescent proteins is important for the design of proteins with improved properties. Here, we present the results of electronic structure calculations identifying the nature of a blue intermediate, a key species in the process of the red chromophore formation in DsRed, TagRFP, fluorescent timers, and PAmCherry. The chromophore of the blue intermediate has a structure in which the π-system of the imidazole ring is extended by the acylimine bond, which can be represented by the model N-[(5-hydroxy-1H-imidazole-2yl)methylidene]acetamide (HIMA) compound. Ab initio and QM/MM calculations of the isolated model and protein-bound (mTagBFP) chromophores identify the anionic form of HIMA as the only structure that has absorption that is consistent with the experiment and is stable in the protein binding pocket. The anion and zwitterion are the only protonation forms of HIMA whose absorption (421 and 414 nm, or 2.95 and 3.00 eV) matches the experimental spectrum of the blue form in DsRed (the absorption maximum is 408 nm or 3.04 eV) and mTagBFP (400 nm or 3.10 eV). The QM/MM optimization of the protein-bound anionic form results in a structure that is close to the X-ray one, whereas the zwitterionic chromophore is unstable in the protein binding pocket and undergoes prompt proton transfer. The computed excitation energy of the protein-bound anionic form of the mTagBFP-like chromophore (3.04 eV) agrees with the experimental absorption spectrum of the protein. The DsRed-like chromophore formation in red fluorescent proteins is revisited on the basis of ab initio results and verified by directed mutagenesis revealing a key role of the amino acid residue 70, which is the second after the chromophore tripeptide, in the formation process.

Electronic structure calculations of microhydrated model chromophores (in their deprotonated anionic forms) of the photoactive yellow and green fluorescent proteins (PYP and GFP) are reported. Electron-detachment and excitation energies as well as binding energies of mono- and dihydrated isomers are computed and analyzed. Microhydration has different effects on the excited and ionized states. In lower-energy planar isomers, the interaction with one water molecule blueshifts the excitation energies by 0.1-0.2 eV, whereas the detachment energies increase by 0.4-0.8 eV. The important consequence is that microhydration by just one water molecule converts the resonance (autoionizing) excited states of the bare chromophores into bound states. In the lower-energy microhydrated clusters, interactions with water have negligible effect on the chromophore geometry; however, we also identified higher-energy dihydrated clusters of PYP in which two water molecules form hydrogen-bonding network connecting the carboxylate and phenolate moieties and the chromophore is strongly distorted resulting in a significant shift of excitation energies (up to 0.6 eV).

The effect of the protein environment on the electronic structure of the green fluorescent protein (GFP) chromophore is investigated by QM/MM (quantum mechanics/molecular mechanics) calculations. The protein has very small effect on the excitation energy of the bright absorbing and the lowest triplet states of the anionic GFP chromophore, deprotonated 4-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI) anion, however, it increases vertical detachment energy from 2.5 eV (gas-phase deprotonated HBDI anion) to 5.0 eV (solvated protein). We also investigated possible existence of the charge-transfer-to-solvent (CTTS) states associated with the GFP chromophore. Although precursors of such states appear in cluster calculations, a tightly packed structure of the protein prevents the formation of the CTTS states in this system. Motivated by a recently discovered new type of photoconversion, oxidative redding, we characterized the redox properties of GFP. The computed standard reduction potential of the anionic form of GFP is 0.47 V (for the GFP(•) + 1e → GFP(-) reaction), and the reduction potential at physiological conditions (pH 7, T = 25 °C) is 0.06 V.

A theoretical study of the electronic structure of the photoactive yellow protein (PYP) model chromophore, para-coumaric acid (p-CA), is presented. Electronically excited states of the phenolate and carboxylate isomers of the deprotonated p-CA are characterized by high-level ab initio methods including state-specific and multistate multireference pertrubation theory (SS-CASPT2, and MS-CASPT2), equation-of-motion coupled-cluster methods with single and double substitutions (EOM-CCSD) and with an approximate account of triple excitations (CC3). We found that the two isomers have distinctly different patterns of ionization and excitation energies. Their excitation energies differ by more than 1 eV, in contradiction to the experimental report [Rocha-Rinza et al., J. Phys. Chem. A 113, 9442 (2009)]. The calculations confirm metastable (autoionizing) character of the valence excited states of both phenolate and carboxylate isomers of p-CA(-) in the gas phase. The type of resonance is different in the two forms. In the phenolate, the excited state lies above the detachment continuum (a shape resonance), whereas in the carboxylate the excited π→π(*) state lies below the π-orbital ionization continuum, but is above the states derived from ionization from three other orbitals (Feshbach resonance). The computed oscillator strength of the bright electronic state in the phenolate is higher than in the carboxylate, in agreement with Hückel's model predictions. The analysis of photofragmentation channels shows that the most probable products for the methylated derivatives of the phenolate and carboxylate forms of p-CA(-) are CH(3), CH(2)O and CH(3), CH(2)O, CO(2), respectively, thus suggesting an experimental probe that may discriminate between the two isomers.

A combined theoretical and experimental study of the effect of microhydration on ionization energies (IEs) of thymine is presented. The experimental IEs are derived from photoionization efficiency curves recorded using tunable synchrotron VUV radiation. The onsets of the PIE curves are 8.85 +/- 0.05, 8.60 +/- 0.05, 8.55 +/- 0.05, and 8.40 +/- 0.05 eV for thymine, thymine mono-, di-, and trihydrates, respectively. The computed (EOM-IP-CCSD/cc-pVTZ) AIEs are 8.90, 8.51, 8.52, and 8.35 eV for thymine and the lowest isomers of thymine mono-, di-, and tri-hydrates. Due to large structural relaxation, the Franck-Condon factors for the 0 <-- 0 transitions are very small shifting the apparent PIE onsets to higher energies. Microsolvation strongly affects IEs of thymine--the addition of each water molecule reduces the first vertical IE by 0.10-0.15 eV. The adiabatic IE decreases even more (up to 0.4 eV). The magnitude of the effect varies for different ionized states and for different isomers. For the ionized states that are localized on thymine the dominant contribution to the IE reduction is the electrostatic interaction between the delocalized positive charge on thymine and the dipole moment of the water molecule.

We report high-level ab initio calculations and single-photon ionization mass spectrometry study of ionization of adenine (A), thymine (T), cytosine (C), and guanine (G). For thymine and adenine, only the lowest-energy tautomers were considered, whereas for cytosine and guanine we characterized the five lowest-energy tautomeric forms. The first adiabatic and several vertical ionization energies were computed using the equation-of-motion coupled-cluster method for ionization potentials with single and double substitutions. Equilibrium structures of the cationic ground states were characterized by DFT with the ωB97X-D functional. The ionization-induced geometry changes of the bases are consistent with the shapes of the corresponding molecular orbitals. For the lowest-energy tautomers, the magnitude of the structural relaxation decreases in the following series, G > C > A > T, the respective relaxation energies being 0.41, 0.32, 0.25, and 0.20 eV. The computed adiabatic ionization energies (8.13, 8.89, 8.51-8.67, and 7.75-7.87 eV for A, T, C, and G, respectively) agree well with the onsets of the photoionization efficiency (PIE) curves (8.20 ± 0.05, 8.95 ± 0.05, 8.60 ± 0.05, and 7.75 ± 0.05 eV). Vibrational progressions for the S(0)-D(0) vibronic bands computed within double-harmonic approximation with Duschinsky rotations are compared with previously reported experimental photoelectron spectra and differentiated PIE curves.

A combined theoretical and experimental study of the ionized dimers of thymine and adenine, TT, AA, and AT, is presented. Experimentally observed and computed adiabatic and vertical ionization energies (IEs) for monomers and dimers as well as thresholds for the appearance of the protonated species are reported and analyzed. Non-covalent interactions strongly affect the observed IEs. The magnitude and the nature of the effect is different for different isomers of the dimers. The computations reveal that for TT, the largest changes in vertical IEs (0.4 eV) relative to the monomer occur in asymmetric H-bonded and symmetric pi-stacked isomers, whereas in the lowest-energy symmetric H-bonded dimer the shift in IEs is much smaller (0.2 eV). The origin of the shift and the character of the ionized states is different in asymmetric H-bonded and symmetric stacked isomers. In the former, the initial hole is localized on one of the fragments, and the shift is due to the electrostatic stabilization of the positive charge of the ionized fragment by the dipole moment of the neutral fragment. In the latter, the hole is delocalized, and the change in IE is proportional to the overlap of the fragments' MOs. Relative to TT, the shifts in AA and AT are much smaller due to a less efficient overlap, smaller dipole of A and the large energy gap between ionized states of A and T monomers in the case of AT dimer. The ionization of the H-bonded dimers results in barrierless (or nearly barrierless) proton transfer, whereas the pi-stacked dimers relax to structures with the hole stabilized by the delocalization or electrostatic interactions.

We report on gas-phase experimental and theoretical studies on the neutral form of the green-fluorescent protein (GFP) chromophore using six different models, each carrying a spectator positive charge. Theoretical studies were carried out to quantify the effect of the spectator charge on the absorption maximum of the true neutral. The study also includes models having the possibility of forming intra-molecular hydrogen bonds, and their effect on the absorption profile is analyzed. The charge redistribution caused by a strong intra-molecular hydrogen bond was found to give rise to a red shift in going from non-hydrogen bonded to hydrogen bonded models. For the non-hydrogen bonded models, the length of the side chain as well as the group carrying the spectator charge, was varied to explore the possibility of shifts in absorption maximum due to these variations. No shifts were observed. The implications of these results in tuning the absorption maximum of the neutral form of the GFP chromophores are discussed.

Photoabsorption spectra of deprotonated trans p-coumaric acid and two of its methyl substituted derivatives have been studied in gas phase both experimentally and theoretically. We have focused on the spectroscopic effect of the location of the two possible deprotonation sites on the trans p-coumaric acid which originate to either a phenoxide or a carboxylate. Surprisingly, the three chromophores were found to have the same absorption maximum at 430 nm, in spite of having different deprotonation positions. However, the absorption of the chromophore in polar solution is substantially different for the distinct deprotonation locations. We also report on the time scales and pathways of relaxation after photoexcitation for the three photoactive yellow protein chromophore derivatives. As a result of these experiments, we could detect the phenoxide isomer within the deprotonated trans p-coumaric acid in gas phase; however, the occurrence of the carboxylate is uncertain. Several computational methods were used simultaneously to provide insights and assistance in the interpretation of our experimental results. The calculated excitation energies S(0)-S(1) are in good agreement with experiment for those systems having a negative charge on a phenoxide moiety. Although our augmented multiconfigurational quasidegenerate perturbation theory calculations agree with experiment in the description of the absorption spectrum of anions with a carboxylate functional group, there are some puzzling disagreements between experiment and some calculational methods in the description of these systems.

The fluorescent protein asFP595 is a promising photoswitchable biomarker for studying processes in living cells. We present the results of a high level theoretical study of photoabsorption properties of the model asFP595 chromophore molecule in biologically relevant protonation states: anionic, zwitterionic, and neutral. Ground state equilibrium geometry parameters are optimized in the PBE0/(aug)-cc-pVDZ density functional theory approximation. An augmented version of multiconfigurational quasidegenerate perturbation theory (aug-MCQDPT2) following the state-averaged CASSCF/(aug)-cc-pVDZ calculations is used to estimate the vertical S0-S1 excitation energies for all chromophore species. An accuracy of this approach is validated by comparing the computed estimates of the S0-S1 absorption maximum of the closely related chromophore from the DsRed protein to the known experimental value in the gas phase. An influence of the CASSCF active space on the aug-MCQDPT2 excitation energies is analyzed. The zwitterionic form of the asFP595 chromophore is found to be the most sensitive to a particular choice and amount of active orbitals. This observation is explained by the charge-transfer type of the S0-S1 transition involving the entire conjugated pi-electron system for the zwitterionic protonation state. According to the calculation results, the anionic form in the trans conformation is found to possess the most red-shifted absorption band with the maximum located at 543 nm. The bands of the zwitterionic and neutral forms are considerably blue-shifted compared to those of the anionic form. These conclusions are at variance with the results obtained in the TDDFT approximation for the asFP595 chromophore. The absorption wavelengths computed in the aug-MCQDPT2/CASSCF theory are as follows: 543 (535), 470 (476), and 415 (417) nm for the anionic, zwitterionic, and neutral forms of the trans and cis (in parentheses) isomers of the asFP595 chromophore. These data can be used as a reference for further theoretical studies of the asFP595 chromophore in different media and for modeling photoabsorption properties of the asFP595 fluorescent protein.

The aging process of the human lens is associated with accumulation of chromophores and fluorophores that impair visual function. In the present study, we examined the photodissociation of 3-OH-kynurenine and argpyrimidine. Furthermore, absorption spectra obtained in gas phase using an electrostatic ion storage ring were studied as gas phase absorption have been shown to be more similar to the in vivo condition than absorption spectra obtained in the liquid phase. Experimental results were compared to theoretical modeling using the multistate, multireference perturbation theory approach combined with advanced molecular modeling tools to account for the solvent effects and to provide direct support for band assignments. Absorption maxima were determined both experimentally and theoretically and significant differences between the two chromophores were found. In particular, 3-OH-kynurenine demonstrated a blue-shift of more than 130 nm in the aqueous phase compared to the gas-phase due to the existence of different 3-OH-kynurenine conformers, which are stable under different conditions and originate from the interplay between intra- and intermolecular interactions. Photodissociation of argpyrimidine and 3-OH-kynurenine was observed in vacuum thus confirming the results previously obtained in liquid phase demonstrating that the photodestruction takes place in both media.