Light-enabled deracemization of cyclopropanes by Al-salen photocatalysis.

Privileged chiral catalysts-those that share common structural features and are enantioselective across a range of reactions-continue to transform the chemical-research landscape1. In recent years, new reactivity modes have been achieved through excited-state catalysis, processes activated by light, but it is unclear if the selectivity of ground-state privileged catalysts can be matched. Although the interception of photogenerated intermediates by ground-state cycles has partially addressed this challenge2, single, chiral photocatalysts that simultaneously regulate reactivity and selectivity are conspicuously scarce3. So far, precision donor-acceptor recognition motifs remain crucial in enantioselective photocatalyst design4. Here we show that chiral Al-salen complexes, which have well-defined photophysical properties, can be used for the efficient photochemical deracemization5 of cyclopropyl ketones (up to 98:2 enantiomeric ratio (e.r.)). Irradiation at λ = 400 nm (violet light) augments the reactivity of the commercial catalyst to enable reactivity and enantioselectivity to be regulated simultaneously. This circumvents the need for tailored catalyst-substrate recognition motifs. It is predicted that this study will stimulate a re-evaluation of many venerable (ground-state) chiral catalysts in excited-state processes, ultimately leading to the identification of candidates that may be considered 'privileged' in both reactivity models.

Charge Regulation at the Nanoscale as Evidenced from Light-Responsive Nanoemulsions.

Emulsions are indispensable in everyday life, and the demand for emulsions' diversity and control of properties is therefore substantial. As emulsions possess a high internal surface area, an understanding of the oil/water (o/w) interfaces at the molecular level is fundamental but often impaired by experimental limitations to probe emulsion interfaces in situ. Here, we have used light-responsive surfactants (butyl-AAP) that can photoisomerize between E and Z isomers by visible and UV light irradiation to tune the emulsion interfaces. This causes massive changes in the interface tension at the extended o/w interfaces in macroemulsions and a drastic shift in the surfactants' critical micelle concentration, which we show can be used to control both the stability and phase separation. Strikingly different from macroemulsions are nanoemulsions (RH ∼90 nm) as these are not susceptible to E/Z photoisomerization of the surfactants in terms of changes in their droplet size or ζ-potential. However, in situ second-harmonic scattering and pulsed-field gradient nuclear magnetic resonance (NMR) experiments show dramatic and reversible changes in the surface excess of surfactants at the nanoscopic interfaces. The apparent differences in ζ-potentials and surface excess provide evidence for a fixed charge to particle size ratio and the need for counterion condensation to renormalize the particle charge to a critical charge, which is markedly different compared to the behavior of very large particles in macroemulsions. Thus, our findings may have broader implications as the electrostatic stabilization of nanoparticles requires much lower surfactant concentrations, allowing for a more sustainable use of surfactants.

Infra-patellar fat pad-derived mesenchymal stem cells maintain their chondrogenic differentiation potential after arthroscopic harvest with blood-product supplementation.

PURPOSE: Mesenchymal stem cells/medicinal signaling cells (MSCs) possess therapeutic potential and are used in regenerative orthopaedics. The infra-patellar fat pad (IFP) is partially resected during knee arthroscopy (KASC) and contains MSCs. Heat, irrigation, and mechanical stress during KASC may decrease MSC's therapeutic potential. This study assessed MSCs' regenerative potential after arthroscopic IFP harvest and potential effects of two blood products (BP) (platelet-rich plasma (PRP), hyperacute serum (HAS)) on MSCs' viability and chondrogenic differentiation capacity. METHODS: IFP was arthroscopically harvested, isolated, and counted (n = 5). Flow cytometry was used to assess cell viability via staining with annexin V/7-AAD and stemness markers via staining for CD90, CD73, and CD105. MSCs were incubated with blood products, and metabolic activity was determined via an XTT assay. Deposition of cartilage extracellular matrix was determined in histologic sections of chondrogenically differentiated 3D pellet cultures via staining with Alcian Blue. Expression of cartilage-specific genes (SOX9, MMP3/13, ACAN, COL1/2) was analyzed via quantitative PCR. RESULTS: MSC isolation from IFP yielded 2.66*106 ± 1.49*106 viable cells from 2.7 (0.748) g of tissue. MSC markers (CD 90/105/73) were successfully detected and annexin V staining showed 81.5% viable cells. XTT showed increased metabolic activity. Within the BP groups, this increase was significant (days 0-14, p < 0.05). PCR showed expression of cartilage-specific genes in each group. COL2 (p < 0.01) as well as ACAN (p < 0.001) expression levels were significantly higher in the HAS group. Histology showed successful differentiation. CONCLUSION: Arthroscopic harvest of IFP-MSCs yields sufficient cells with maintained regenerative potential and viability. Blood products further enhance MSCs' viability.

On the accuracy of orbital based multi-level approaches for closed-shell transition metal chemistry.

In this work, we investigate the accuracy of the local molecular orbital molecular orbital (LMOMO) scheme and projection-based wave function-in-density functional theory (WF-in-DFT) embedding for the prediction of reaction energies and barriers of typical reactions involving transition metals. To analyze the dependence of the accuracy on the system partitioning, we apply a manual orbital selection for LMOMO as well as the so-called direct orbital selection (DOS) for both approaches. We benchmark these methods on 30 closed shell reactions involving 16 different transition metals. This allows us to devise guidelines for the manual selection as well as settings for the DOS that provide accurate results within an error of 2 kcal mol-1 compared to local coupled cluster. To reach this accuracy, on average 55% of the occupied orbitals have to be correlated with coupled cluster for the current test set. Furthermore, we find that LMOMO gives more reliable relative energies for small embedded regions than WF-in-DFT embedding.

Automatic Generation of Auxiliary Basis Sets in Spherical Representation Using the Cholesky Decomposition.

Density fitting techniques that use automatically generated auxiliary basis sets generally rely on the formation of basis function products. Recently, Lehtola [ J. Chem. Theory Comput. 2021, 17, 6886-6900] presented a procedure making use of a purely spherical representation by adding auxiliary basis functions coupled to the required angular momentum quantum numbers for the product of spherical harmonics and then removing linear dependencies by means of a Cholesky decomposition. In this work, we extend this idea by making use of the explicit equations for the product of two spherical harmonics in the angular part of the basis function product. Some of the resulting terms are not directly accessible when popular standard integral libraries are used, which could prevent the widespread use of the exact product form. For these terms, we introduce four approximations of increasing sophistication that require integrals involving only standard Gaussian-type orbitals and thus can be computed with standard libraries. We assess the accuracy of the different schemes in the context of the aCD for the reconstruction of the electron repulsion integral matrix and absolute and relative single point energies and in the framework of optimally tuned range-separated hybrid functionals.

Sterically Allowed H-type Supramolecular Polymerizations.

The functionalization of π-conjugated scaffolds with sterically demanding substituents is a widely used tactic to suppress cofacial (H-type) stacking interactions, which may even inhibit self-assembly. Contrary to expectations, we demonstrate herein that increasing steric effects can result in an enhanced thermodynamic stability of H-type supramolecular polymers. In our approach, we have investigated two boron dipyrromethene (BODIPY) dyes with bulky phenyl (2) and mesityl (3) meso-substituents and compared their self-assembly in nonpolar media with that of a parent meso-methyl BODIPY 1 lacking bulky groups. While the enhanced steric demand induces pathway complexity, the superior thermodynamic stability of the H-type pathways can be rationalized in terms of additional enthalpic gain arising from intermolecular C-H⋅⋅⋅F-B interactions of the orthogonally arranged aromatic substituents, which overrule their inherent steric demand. Our findings underline the importance of balancing competing non-covalent interactions in self-assembly.

Reliable Isotropic Electron-Paramagnetic-Resonance Hyperfine Coupling Constants from the Frozen-Density Embedding Quasi-Diabatization Approach.

We present a systematic benchmark of isotropic electron-paramagnetic-resonance hyperfine coupling constants calculated for radical cation and anion complexes of molecules contained in the S22 test set using the frozen-density embedding quasi-diabatization (FDE-diab) approach. The results are compared to those from Kohn-Sham density-functional theory and frozen-density embedding, employing the domain-based local pair natural orbital coupled cluster singles and doubles method as a reference. We demonstrate that our new approach outperforms frozen-density embedding in all cases and provides reliable hyperfine couplings for radical cations using rather simple generalized-gradient approximation-type functionals. By contrast, more sophisticated and computationally less efficient exchange-correlation approximations are required for Kohn-Sham density-functional theory. For the radical anions, FDE-diab can at least provide an accuracy similar to that of Kohn-Sham density-functional theory. Finally, we demonstrate the computational advantages of FDE-diab for a π-stacked benzene octamer radical cation.

Subsystem density-functional theory: A reliable tool for spin-density based properties.

Subsystem density-functional theory compiles a set of features that allow for efficiently calculating properties of very large open-shell radical systems such as organic radical crystals, proteins, or deoxyribonucleic acid stacks. It is computationally less costly than correlated ab initio wave function approaches and can pragmatically avoid the overdelocalization problem of Kohn-Sham density-functional theory without employing hard constraints on the electron-density. Additionally, subsystem density-functional theory calculations commonly start from isolated fragment electron densities, pragmatically preserving a priori specified subsystem spin-patterns throughout the calculation. Methods based on subsystem density-functional theory have seen a rapid development over the past years and have become important tools for describing open-shell properties. In this Perspective, we address open questions and possible developments toward challenging future applications in connection with subsystem density-functional theory for spin-dependent properties.

Orbital pair selection for relative energies in the domain-based local pair natural orbital coupled-cluster method.

For the accurate computation of relative energies, domain-based local pair natural orbital coupled-cluster [DLPNO-CCSD(T0)] has become increasingly popular. Even though DLPNO-CCSD(T0) shows a formally linear scaling of the computational effort with the system size, accurate predictions of relative energies remain costly. Therefore, multi-level approaches are attractive that focus the available computational resources on a minor part of the molecular system, e.g., a reaction center, where changes in the correlation energy are expected to be the largest. We present a pair-selected multi-level DLPNO-CCSD(T0) ansatz that automatically partitions the orbital pairs according to their contribution to the overall correlation energy change in a chemical reaction. To this end, the localized orbitals are mapped between structures in the reaction; all pair energies are approximated through computationally efficient semi-canonical second-order Møller-Plesser perturbation theory, and the orbital pairs for which the pair energies change significantly are identified. This multi-level approach is significantly more robust than our previously suggested, orbital selection-based multi-level DLPNO-CCSD(T0) ansatz [M. Bensberg and J. Neugebauer, J. Chem. Phys. 155, 224102 (2021)] for reactions showing only small changes in the occupied orbitals. At the same time, it is even more efficient without added input complexity or accuracy loss compared to the full DLPNO-CCSD(T0) calculation. We demonstrate the accuracy of the multi-level approach for a total of 128 chemical reactions and potential energy curves of weakly interacting complexes from the S66x8 benchmark set.

Origin invariant electronic circular dichroism in the length dipole gauge without London atomic orbitals.

We present a method for obtaining origin-independent electronic circular dichroism (ECD) in the length-gauge representation LG(OI) without the usage of London atomic orbitals. This approach builds upon the work by Caricato [J. Chem. Phys. 153, 151101 (2020)] and is applied to rotatory strengths and ECD spectra from damped response theory. Numerical results are presented for time-dependent Hartree-Fock and density-functional theory, the second-order algebraic diagrammatic construction method, and linear-response coupled-cluster theory with singles and approximate doubles. We can support the finding that the common choice of placing the gauge origin in the center of mass of a molecule in conventional length-gauge calculations involving chiroptical properties might not be optimal and show that LG(OI) is a valuable alternative for the origin-independent calculation of ECD spectra. We show that, for a limited test set, the convergence of the rotatory strengths calculated with the LG(OI) approach toward the basis-set limit tends to be faster than for the established velocity gauge representation. Relationships between the sum-over-states expression of the optical rotation in the LG(OI) framework and its representation in terms of response functions are analyzed.

Synthesis and Reactivity of a Neutral Homocyclic Silylene.

Isolation of the neutral homocyclic silylene 2 is possible via amine ligand abstraction with potassium graphite (KC8 ) and subsequent reaction with SiMe3 Cl from a bicyclic silicon(I) amide J. This reaction proceeds via an anionic homoaromatic silicon ring compound 1 as an intermediate. The twofold-coordinated silicon atom in the homocyclic silylene 2 is stabilized by an allyl-type π-electron delocalization. 2 reacts in an oxidative addition with two equivalents of MeOH and in cycloadditions with ethene, phenylacetylene, diphenylacetylene and with 2,3-dimethyl-1,3-butadiene to afford novel functionalized ring compounds.

Electronic effects in profluorescent benzotriazinyl radicals: a combined experimental and theoretical study.

The synthesis, photophysical characterization, and quantum chemical calculations of a series of benzotriazinyl radicals and their styryl radical trapping products are presented. The benzotriazinyl radicals are non-luminescent but surprisingly the corresponding styryl radical trapping products exhibit high fluorescence quantum yields (up to 60% in some cases), making them highly valuable probes or labels. Additionally, the influence of the substitution pattern on the optical properties of the radical trapping products was observed experimentally and interpreted by means of quantum chemical calculations. Specific substitution patterns showed a bathochromic shift compared to the unsubstituted compound. Computationally, it was shown that this substitution pattern leads to a stronger energetic stabilization of the lowest unoccupied molecular orbital than the highest occupied molecular orbital. Analysis of the influence of the substitution pattern on the optical properties showed a bathochromic shift in several examples, which was interpreted by means of quantum chemical calculations.

Direct orbital selection within the domain-based local pair natural orbital coupled-cluster method.

Domain-based local pair natural orbital coupled cluster (DLPNO-CC) has become increasingly popular to calculate relative energies (e.g., reaction energies and reaction barriers). It can be applied within a multi-level DLPNO-CC-in-DLPNO-CC ansatz to reduce the computational cost and focus the available computational resources on a specific subset of the occupied orbitals. We demonstrate how this multi-level DLPNO-CC ansatz can be combined with our direct orbital selection (DOS) approach [M. Bensberg and J. Neugebauer, J. Chem. Phys. 150, 214106 (2019)] to automatically select orbital sets for any multi-level calculation. We find that the parameters for the DOS procedure can be chosen conservatively such that they are transferable between reactions. The resulting automatic multi-level DLPNO-CC method requires no user input and is extremely robust and accurate. The computational cost is easily reduced by a factor of 3 without sacrificing accuracy. We demonstrate the accuracy of the method for a total of 61 reactions containing up to 174 atoms and use it to predict the relative stability of conformers of a Ru-based catalyst.

Multi-state formulation of the frozen-density embedding quasi-diabatization approach.

We present a multi-state implementation of the recently developed frozen-density embedding diabatization (FDE-diab) methodology [D. G. Artiukhin and J. Neugebauer, J. Chem. Phys. 148, 214104 (2018)] in the Serenity program. The new framework extends the original approach such that any number of charge-localized quasi-diabatic states can be coupled, giving an access to calculations of ground and excited state spin-density distributions as well as to excitation energies. We show that it is possible to obtain results similar to those from correlated wave function approaches such as the complete active space self-consistent field method at much lower computational effort. Additionally, we present a series of approximate computational schemes, which further decrease the overall computational cost and systematically converge to the full FDE-diab solution. The proposed methodology enables computational studies on spin-density distributions and related properties for large molecular systems of biochemical interest.

Azo bond formation on metal surfaces.

The formation of azo compounds via redox cross-coupling of nitroarenes and arylamines, challenging in solution phase chemistry, is achieved by on-surface chemistry. Reaction products are analyzed with a cryogenic scanning tunneling microscope (STM) and X-ray photoelectron spectroscopy (XPS). By using well-designed precursors containing both an amino and a nitro functionality, azo polymers are prepared on surface via highly efficient nitro-amino cross-coupling. Experiments conducted on other substrates and surface orientations reveal that the metal surface has a significant effect on the reaction efficiency. The reaction was further found to proceed from partially oxidized/reduced precursors in dimerization reactions, shedding light on the mechanism that was studied by DFT calculations.

Design of Ru(II)-NHC-Diamine Precatalysts Directed by Ligand Cooperation: Applications and Mechanistic Investigations for Asymmetric Hydrogenation.

A modular synthesis of Ru(II)-NHC-diamine complexes from readily available chiral N-heterocyclic carbenes (NHCs) and chiral diamines is disclosed for the first time. The well-defined Ru(II)-NHC-diamine complexes show unique structure and coordination chemistry including an unusual tridentate coordination effect of 1,2-diphenylethylenediamine. The isolated air- and moisture-stable Ru(II)-NHC-diamine complexes act as versatile precatalysts for the asymmetric hydrogenation of isocoumarines, benzothiophene 1,1-dioxides, and ketones. Moreover, on the basis of the identification of reaction intermediates by stoichiometric reactions and NMR experiments, together with the DFT calculations, a possible catalytic cycle was proposed.

Aryl Triflates in On-Surface Chemistry.

The reactivity of aryl triflates in on-surface C-C coupling is reported. It is shown that the triflate group in aryl triflates enables regioselective homo coupling with preceding or concomitant hydrodetriflation on Cu(111). Three different symmetrical π-systems with two and three triflate functionalities were used as monomers leading to oligomeric conjugated π-systems. The cascade, comprising different intermediates at different reaction temperatures as observed for one of the molecules, proceeds via initial removal of the trifluoromethyl sulfonyl group to give an aryloxy radical which in turn is deoxygenated to the corresponding aryl radical. Thermodynamically driven regioselective 1,2-hydrogen atom transfer leads to a translocated aryl radical which in turn undergoes coupling. For a sterically more hindered bistriflate, where one ortho position was blocked, dehydrogenative coupling occurred at remote position with good regioselectivity. Starting materials, intermediates as well as products were analyzed by scanning tunneling microscopy. Structures and suggested mechanism were further supported by DFT calculations.

Subsystem density-functional theory for interacting open-shell systems: spin densities and magnetic exchange couplings.

We investigate the possibility of describing interacting open-shell systems in high-spin and broken-symmetry (BS) states with subsystem density-functional theory (sDFT). This subsystem method typically starts from the electronic-structure results obtained for individual systems, for which the spin states can be individually defined. Through the confining effect of the embedding potential and/or the use of monomer basis sets, these individual spin states can be preserved in sDFT calculations. This offers the possibility of easy convergence to broken-symmetry states with arbitrary local spin patterns. We show that the resulting spin densities are in very good agreement with successfully converged broken-symmetry Kohn-Sham density-functional theory (KS-DFT) calculations. Yet sDFT can even cure those BS cases where KS-DFT suffers from convergence problems or convergence to undesired spin states. In contrast to KS-DFT, the sDFT-results only show a mild exchange-correlation functional dependence. We also show that magnetic coupling constants from sDFT are not satisfactory with standard approximations for the non-additive kinetic energy. When this component is evaluated "exactly", i.e. based on potential reconstruction, however, the magnetic coupling constants derived from spin-state energy differences are greatly improved. Hence, the interacting radicals studied here represent cases where even (semi-)local approximations for the non-additive kinetic-energy potential work well, while the parent energy functionals do not yield satisfactory results for spin-state energy differences.

Density functional theory based embedding approaches for transition-metal complexes.

Transition metal species are commonly discussed by considering the metal atom embedded in a ligand environment. This apparently makes them interesting targets for modern embedding strategies based on Kohn-Sham density functional theory (DFT), which aim at modelling accurate predictions for large systems by combining different quantum chemical methods. In this perspective, we will focus on subsystem density functional theory and projection-based embedding. We review the developments in the field for transition metal species, demonstrate benefits, drawbacks and analyse error sources of the different strategies using the example of chromium hexacarbonyle, before giving a perspective where the field is currently heading.

Electronic couplings for photo-induced processes from subsystem time-dependent density-functional theory: The role of the diabatization.

Subsystem time-dependent density-functional theory (sTDDFT) making use of approximate non-additive kinetic energy (NAKE) functionals is known to be capable of describing excitation energy transfer processes in a variety of applications. Here, we show that sTDDFT, especially when combined with projection-based embedding (PbE), can be employed for the entire range of photo-induced electronic couplings essential for modeling photophysical properties of complex chemical and biological systems and therefore represents a complete toolbox for this class of problems. This means that it is capable of capturing the interaction/coupling associated with local- and charge-transfer (CT) excitons. However, this requires the choice of a reasonable diabatic basis. We therefore propose different diabatization strategies of the virtual orbital space in PbE-sTDDFT and show how CT excitations can be included in sTDDFT using NAKE functionals via a phenomenological approach. Finally, these electronic couplings are compared to couplings from a multistate fragment excitation difference (FED)-fragment charge difference (FCD) diabatization procedure. We show that both procedures, multistate FED-FCD and sTDDFT (with the right diabatization procedure chosen), lead to an overall good agreement for the electronic couplings, despite differences in their general diabatization strategy. We conclude that the entire range of photo-induced electronic couplings can be obtained using sTDDFT (with the right diabatization procedure chosen) in a black-box manner.