Abstract In this contribution, we describe a set of three chlorinated bridged ethers with varying numbers of sulfur and oxygen atoms. The substitution leads to highly emissive compounds with tunable photophysical properties in relationship to their state of aggregation, i.?e. in solution, as aggregates and in the solid state. Additionally, an in-depth X-ray diffractometric analysis supported by a Hirshfeld study of non-covalent interactions and quantum chemical simulations was carried out. As the outcome, it was found that the content of sulfur in the compounds regulates the tuning of emission in solution as well as in the aggregated states as a consequence of their variation of planarity.

Chirality (‘handedness’) is a property that underlies a broad variety of phenomena in nature. Chiral molecules appear in two forms, and each is a mirror image of the other, the two enantiomers. The chirality of molecules is associated with their optical activity, and circular dichroism is commonly applied to identify the handedness of chiral molecules. Recently, the chiral induced spin selectivity (CISS) effect was established, according to which transfer of electrons within chiral molecules depends on the electron’s spin. Which spin is preferred depends on the handedness of the chiral molecule and the direction of motion of the electron. Several experiments in the past indicated that there may be a relation between the optical activity of the molecules and their spin selectivity. Here, we show that for a molecule containing several stereogenic axes, when adsorbed on a metal substrate, the peaks in the CD spectra have the same signs for the two enantiomers. This is not the case when the molecules are adsorbed on a nonmetallic substrate or dissolved in solution. Quantum chemical simulations are able to explain the change in the CD spectra upon adsorption of the molecules on conductive and nonconductive surfaces. Surprisingly, the CISS properties are similar for the two enantiomers when adsorbed on the metal substrate, while when the molecules are adsorbed on nonmetallic surface, the preferred spin depends on the molecule handedness. This correlation between the optical activity and the CISS effect indicates that the CISS effect relates to the global polarizability of the molecule.Chirality (‘handedness’) is a property that underlies a broad variety of phenomena in nature. Chiral molecules appear in two forms, and each is a mirror image of the other, the two enantiomers. The chirality of molecules is associated with their optical activity, and circular dichroism is commonly applied to identify the handedness of chiral molecules. Recently, the chiral induced spin selectivity (CISS) effect was established, according to which transfer of electrons within chiral molecules depends on the electron’s spin. Which spin is preferred depends on the handedness of the chiral molecule and the direction of motion of the electron. Several experiments in the past indicated that there may be a relation between the optical activity of the molecules and their spin selectivity. Here, we show that for a molecule containing several stereogenic axes, when adsorbed on a metal substrate, the peaks in the CD spectra have the same signs for the two enantiomers. This is not the case when the molecules are adsorbed on a nonmetallic substrate or dissolved in solution. Quantum chemical simulations are able to explain the change in the CD spectra upon adsorption of the molecules on conductive and nonconductive surfaces. Surprisingly, the CISS properties are similar for the two enantiomers when adsorbed on the metal substrate, while when the molecules are adsorbed on nonmetallic surface, the preferred spin depends on the molecule handedness. This correlation between the optical activity and the CISS effect indicates that the CISS effect relates to the global polarizability of the molecule.

Multiscale simulations have been established as a powerful tool to calculate and predict excitation energies in complex systems such as photoreceptor proteins. In these simulations the chromophore is typically treated using quantum mechanical (QM) methods while the protein and surrounding environment are described by a classical molecular mechanics (MM) force field. The electrostatic interactions between these regions are often treated using electrostatic embedding where the point charges in the MM region polarize the QM region. A more sophisticated treatment accounts also for the polarization of the MM region. In this work, the effect of such a polarizable embedding on excitation energies was benchmarked and compared to electrostatic embedding. This was done for two different proteins, the lipid membrane-embedded jumping spider rhodopsin and the soluble cyanobacteriochrome Slr1393g3. It was found that the polarizable embedding scheme produces absorption maxima closer to experimental values. The polarizable embedding scheme was also benchmarked against expanded QM regions and found to be in qualitative agreement. Treating individual residues as polarizable recovered between 50% and 71% of the QM improvement in the excitation energies, depending on the system. A detailed analysis of each amino acid residue in the chromophore binding pocket revealed that aromatic residues result in the largest change in excitation energy compared to the electrostatic embedding. Furthermore, the computational efficiency of polarizable embedding allowed it to go beyond the binding pocket and describe a larger portion of the environment, further improving the results.

Design and synthesis of orthogonally protected monosaccharide building blocks are crucial for the preparation of well-defined oligosaccharides in a stereo- and regiocontrolled manner. Selective introduction of protecting groups to partially protected monosaccharides is nontrivial due to the often unpredictable electronic, steric, and conformational effects of the substituents. Abolished reactivity toward a commonly used Lewis base-catalyzed acylation of O-2 was observed in conformationally restricted 4,6-O-benzylidene-3-O-Nap galactoside. Investigation of analogous systems, crystallographic characterization, and quantum chemical calculations highlighted the overlooked conformational and steric considerations, the combination of which produces a unique passivity of the 2-OH nucleophile. Evaluating the role of electrophile counterion and auxiliary base in the acylation of the sterically crowded and conformationally restricted galactoside system revealed an alternative Brønsted base-driven reaction pathway via nucleophilic activation. Insights gained from this model system were utilized to access the target galactoside intermediate within the envisioned synthetic route. The acylation strategy described herein can be implemented in future syntheses of key monomeric building blocks with unique protecting group hierarchies.Design and synthesis of orthogonally protected monosaccharide building blocks are crucial for the preparation of well-defined oligosaccharides in a stereo- and regiocontrolled manner. Selective introduction of protecting groups to partially protected monosaccharides is nontrivial due to the often unpredictable electronic, steric, and conformational effects of the substituents. Abolished reactivity toward a commonly used Lewis base-catalyzed acylation of O-2 was observed in conformationally restricted 4,6-O-benzylidene-3-O-Nap galactoside. Investigation of analogous systems, crystallographic characterization, and quantum chemical calculations highlighted the overlooked conformational and steric considerations, the combination of which produces a unique passivity of the 2-OH nucleophile. Evaluating the role of electrophile counterion and auxiliary base in the acylation of the sterically crowded and conformationally restricted galactoside system revealed an alternative Brønsted base-driven reaction pathway via nucleophilic activation. Insights gained from this model system were utilized to access the target galactoside intermediate within the envisioned synthetic route. The acylation strategy described herein can be implemented in future syntheses of key monomeric building blocks with unique protecting group hierarchies.

Cyanobacteriochromes are bistable photoreceptor proteins with desirable photochemical properties for biotechnological applications, such as optogenetics or fluorescence microscopy. Here, we investigate Slr1393-g3, a cyanobacteriochrome that reversibly photoswitches between a red-absorbing (Pr) and green-absorbing (Pg) form. We applied advanced IR spectroscopic methods to track the sequence of intermediates during the photocycle over many orders of magnitude in time. In the conversion from Pg to Pr, we have revealed a new intermediate with distinct spectroscopic features in the IR, which precedes Pr formation using transient IR spectroscopy. In addition, stationary and transient 2D IR experiments measured the vibrational couplings between different groups of the chromophore and the protein in these intermediate states, as well as their structural disorder. Anharmonic QM/MM calculations predict spectra in good agreement with experimental 2D IR spectra of the initial and final states of the photocycle. They facilitate the assignment of the IR spectra that serve as a basis for the interpretation of the spectroscopic results and suggest structural changes of the intermediates along the photocycle.Cyanobacteriochromes are bistable photoreceptor proteins with desirable photochemical properties for biotechnological applications, such as optogenetics or fluorescence microscopy. Here, we investigate Slr1393-g3, a cyanobacteriochrome that reversibly photoswitches between a red-absorbing (Pr) and green-absorbing (Pg) form. We applied advanced IR spectroscopic methods to track the sequence of intermediates during the photocycle over many orders of magnitude in time. In the conversion from Pg to Pr, we have revealed a new intermediate with distinct spectroscopic features in the IR, which precedes Pr formation using transient IR spectroscopy. In addition, stationary and transient 2D IR experiments measured the vibrational couplings between different groups of the chromophore and the protein in these intermediate states, as well as their structural disorder. Anharmonic QM/MM calculations predict spectra in good agreement with experimental 2D IR spectra of the initial and final states of the photocycle. They facilitate the assignment of the IR spectra that serve as a basis for the interpretation of the spectroscopic results and suggest structural changes of the intermediates along the photocycle.

Many simulation methods concerning solvated molecules are based on the assumption that the solvated species and the solvent can be characterized by some representative structures of the solute and some embedding potential corresponding to this structure. While the averaging of the solvent configurations to obtain an embedding potential has been studied in great detail, this hinges on a single solute structure representation. This assumption is re-examined and generalized for conformationally flexible solutes and tested on 4 nonrigid systems. In this generalized approach, the solute is characterized by a set of representative structures and the corresponding embedding potentials. The representative structures are identified by means of subdividing the statistical ensemble, which in this work is generated by a constant-temperature molecular dynamics simulation. The embedding potential defined in the Frozen-Density Embedding Theory is used to characterize the average effect of the solvent in each subensemble. The numerical examples concern the vertical excitation energies of protonated retinal Schiff bases in protein environments. It is comprehensively shown that subensemble averaging leads to huge computational savings compared with explicit averaging of the excitation energies in the whole ensemble while introducing only minor errors in the case of the systems examined.Many simulation methods concerning solvated molecules are based on the assumption that the solvated species and the solvent can be characterized by some representative structures of the solute and some embedding potential corresponding to this structure. While the averaging of the solvent configurations to obtain an embedding potential has been studied in great detail, this hinges on a single solute structure representation. This assumption is re-examined and generalized for conformationally flexible solutes and tested on 4 nonrigid systems. In this generalized approach, the solute is characterized by a set of representative structures and the corresponding embedding potentials. The representative structures are identified by means of subdividing the statistical ensemble, which in this work is generated by a constant-temperature molecular dynamics simulation. The embedding potential defined in the Frozen-Density Embedding Theory is used to characterize the average effect of the solvent in each subensemble. The numerical examples concern the vertical excitation energies of protonated retinal Schiff bases in protein environments. It is comprehensively shown that subensemble averaging leads to huge computational savings compared with explicit averaging of the excitation energies in the whole ensemble while introducing only minor errors in the case of the systems examined.

Photoisomerization of azobenzenes from their stable E isomer to the metastable Z state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the E-to-Z isomerization by using light of a desired color, including red. DESC relies on a combination of a macrocyclic host and a photosensitizer, which act together to selectively bind and sensitize E-azobenzenes for isomerization. The Z isomer lacks strong affinity for and is expelled from the host, which can then convert additional E-azobenzenes to the Z state. In this way, the host?photosensitizer complex converts photon energy into chemical energy in the form of out-of-equilibrium photostationary states, including ones that cannot be accessed through direct photoexcitation. Chemists often strive to push reactions metaphorically uphill toward less energetically favorable products. The challenge is to keep those products from rolling right back down. Gemen et al. report a clever tactic for twisting azobenzene into its higher-energy Z conformation. Specifically, they lured the more stable E isomer into a supramolecular host, along with a photosensitizer. When visible light injects energy to induce the twist, the Z isomer no longer fits in the cavity, so it gets pushed out before more light can twist it back. ?Jake S. Yeston Spatial constraints in a supramolecular host selectively convert azobenzenes to their metastable state under visible light.Photoisomerization of azobenzenes from their stable E isomer to the metastable Z state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the E-to-Z isomerization by using light of a desired color, including red. DESC relies on a combination of a macrocyclic host and a photosensitizer, which act together to selectively bind and sensitize E-azobenzenes for isomerization. The Z isomer lacks strong affinity for and is expelled from the host, which can then convert additional E-azobenzenes to the Z state. In this way, the host?photosensitizer complex converts photon energy into chemical energy in the form of out-of-equilibrium photostationary states, including ones that cannot be accessed through direct photoexcitation. Chemists often strive to push reactions metaphorically uphill toward less energetically favorable products. The challenge is to keep those products from rolling right back down. Gemen et al. report a clever tactic for twisting azobenzene into its higher-energy Z conformation. Specifically, they lured the more stable E isomer into a supramolecular host, along with a photosensitizer. When visible light injects energy to induce the twist, the Z isomer no longer fits in the cavity, so it gets pushed out before more light can twist it back. ?Jake S. Yeston Spatial constraints in a supramolecular host selectively convert azobenzenes to their metastable state under visible light.

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.

Photosystem II reaction centers extract electrons from water, providing the basis of oxygenic life on earth. Among the light-sensitive pigments of the reaction center, a central chlorophyll a dimer, known as the special pair, so far has escaped a complete theoretical characterization of its excited state properties. The close proximity of the special pair pigments gives rise to short-range effects that comprise a coupling between local and charge transfer (CT) excited states as well as other intermolecular quantum effects. Using a multiscale simulation and a diabatization technique, we show that the coupling to CT states is responsible for 45% of the excitonic coupling in the special pair. The other short-range effects cause a nonconservative nature of the circular dichroism spectrum of the reaction center by effectively rotating the electric transition dipole moments of the special pair pigments inverting and strongly enhancing their intrinsic rotational strength.Photosystem II reaction centers extract electrons from water, providing the basis of oxygenic life on earth. Among the light-sensitive pigments of the reaction center, a central chlorophyll a dimer, known as the special pair, so far has escaped a complete theoretical characterization of its excited state properties. The close proximity of the special pair pigments gives rise to short-range effects that comprise a coupling between local and charge transfer (CT) excited states as well as other intermolecular quantum effects. Using a multiscale simulation and a diabatization technique, we show that the coupling to CT states is responsible for 45% of the excitonic coupling in the special pair. The other short-range effects cause a nonconservative nature of the circular dichroism spectrum of the reaction center by effectively rotating the electric transition dipole moments of the special pair pigments inverting and strongly enhancing their intrinsic rotational strength.