Substitution Effect on 2-(Oxazolinyl)-phenols and 1,2,5-Chalcogenadiazole-Annulated Derivatives: Emission-Color-Tunable, Minimalistic Excited-State Intramolecular Proton Transfer (ESIPT)-Based Luminophores.

Minimalistic 2-(oxazolinyl)-phenols substituted with different electron-donating and -withdrawing groups as well as 1,2,5-chalcogenadiazole-annulated derivatives thereof were synthesized and investigated in regard to their emission behavior in solution as well as in the solid state. Depending on the nature of the incorporated substituent and its position, emission efficiencies were increased or diminished, resulting in AIE or ACQ characteristics. Single-crystal analysis revealed J- and H-type packing motifs and a so-far undescribed isolation of ESIPT-based fluorophores in the keto form.

A Two-Step Baromechanical Cycle for Repeated Activation and Deactivation of Mechanophores.

Mechanophores that are embedded in a polymer backbone respond to the application of mechanical stretching forces by geometric changes such as bond rupture. Typically, these structural changes are irreversible, which limits the applicability of functional materials incorporating mechanophores. Using computational methods, we, here, present a general method of restoring a force-activated mechanophore to its deactivated form by using hydrostatic pressure. We use the spiropyran-merocyanine (SP-MC) interconversion to show that repeated activation of the SP mechanophore and deactivation of MC can be achieved by alternating mechanical stretching and hydrostatic compression, respectively. In the baromechanical cycle, MC acts as a "barophore" that responds to hydrostatic pressure by bond formation. The activation and deactivation of SP/MC are understood in terms of strain and electronic effects. Beneficially, this two-step baromechanical cycle can be observed in real time by using UV/vis spectroscopy. Our calculations pave the way for improving the applicability and reusability of force-responsive materials.

Modeling Molecules under Pressure with Gaussian Potentials.

The computational modeling of molecules under high pressure is a growing research area that augments experimental high-pressure chemistry. Here, a new electronic structure method for modeling atoms and molecules under pressure, Gaussians On Surface Tesserae Simulate HYdrostatic Pressure (GOSTSHYP) approach, is introduced. In this method, a set of Gaussian potentials is distributed evenly on the van der Waals surface of the investigated chemical system, leading to a compression of the electron density and the atomic scaffold. Since no parameters other than pressure need to be specified, GOSTSHYP allows straightforward geometry optimizations and ab initio molecular dynamics simulations of chemical systems under pressure for nonexpert users. Calculated energies, bond lengths, and dipole moments under pressure fall within the range of established computational methods for high-pressure chemistry. A Diels-Alder reaction and the cyclotrimerization of acetylene showcase the ability of GOSTSHYP to model pressure-induced chemical reactions. The connection to mechanochemistry is pointed out.

Molecular Magnetizabilities Computed Via Finite Fields: Assessing Alternatives to MP2 and Revisiting Magnetic Exaltations in Aromatic and Antiaromatic Species.

Magnetic properties of molecules such as magnetizabilities represent second order derivatives of the energy with respect to external perturbations. To avoid the need for analytic second derivatives and thereby permit evaluation of the performance of methods where they are not available, a new implementation of quantum chemistry calculations in finite applied magnetic fields is reported. This implementation is employed for a collection of small molecules with the aug-cc-pVTZ basis set to assess orbital optimized (OO) MP2 and a recently proposed regularized variant of OOMP2, called κ-OOMP2. κ-OOMP2 performs significantly better than conventional second order Møller-Plesset (MP2) theory, by reducing MP2's exaggeration of electron correlation effects. As a chemical application, we revisit an old aromaticity criterion called magnetizability exaltation. In lieu of empirical tables or increment systems to generate references, we instead use straight chain molecules with the same formal bond structure as the target cyclic planar conjugated molecules. This procedure is found to be useful for qualitative analysis, yielding exaltations that are typically negative for aromatic species and positive for antiaromatic molecules. One interesting species, N2S2, shows a positive exaltation despite having aromatic characteristics.

The activation efficiency of mechanophores can be modulated by adjacent polymer composition.

The activation efficiency of mechanophores in stress-responsive polymers is generally limited by the competing process of unspecific scission in other parts of the polymer chain. Here it is shown that the linker between the mechanophore and the polymer backbone determines the force required to activate the mechanophore. Using quantum chemical methods, it is demonstrated that the activation forces of three mechanophores (Dewar benzene, benzocyclobutene and gem-dichlorocyclopropane) can be adjusted over a range of almost 300% by modifying the chemical composition of the linker. The results are discussed in terms of changes in electron density, strain distribution and structural parameters during the rupture process. Using these findings it is straightforward to either significantly enhance or reduce the activation rate of mechanophores in stress-responsive materials, depending on the desired use case. The methodology is applied to switch a one-step "gating" of a mechanochemical transformation to a two-step process.

A mechanochemical model for the simulation of molecules and molecular crystals under hydrostatic pressure.

A novel mechanochemical method for the simulation of molecules and molecular crystals under hydrostatic pressure, the eXtended Hydrostatic Compression Force Field (X-HCFF) approach, is introduced. In contrast to comparable methods, the desired pressure can be adjusted non-iteratively and molecules of general shape retain chemically reasonable geometries even at high pressure. The implementation of the X-HCFF approach is straightforward, and the computational cost is practically the same as for regular geometry optimization. Pressure can be applied by using any desired electronic structure method for which a nuclear gradient is available. The results of the X-HCFF for pressure-dependent intramolecular structural changes in the investigated molecules and molecular crystals as well as a simple pressure-induced dimerization reaction are chemically intuitive and fall within the range of other established computational methods. Experimental spectroscopic data of a molecular crystal under pressure are reproduced accurately.

The Mechanism of Flex-Activation in Mechanophores Revealed By Quantum Chemistry.

Flex-activated mechanophores can be used for small-molecule release in polymers under tension by rupture of covalent bonds that are orthogonal to the polymer main chain. Using static and dynamic quantum chemical methods, we here juxtapose three different mechanical deformation modes in flex-activated mechanophores (end-to-end stretching, direct pulling of the scissile bonds, bond angle bendings) with the aim of proposing ways to optimize the efficiency of flex-activation in experiments. It is found that end-to-end stretching, which is a traditional approach to activate mechanophores in polymers, does not trigger flex-activation, whereas direct pulling of the scissile bonds or displacement of adjacent bond angles are efficient methods to achieve this goal. Based on the structural, energetic and electronic effects responsible for these observations, we propose ways of weakening the scissile bonds experimentally to increase the efficiency of flex-activation.

Synthesis and Thermal Investigations of Eleven-Membered Ring Systems Containing One of the Heavier Group 14 Element Atoms Si, Ge, and Sn.

Unique eleven-membered rings containing silicon, germanium, and tin were synthesized in good yields by the reactions of the corresponding 1,2-bis((2-bromothiophen-3-yl)methoxy)benzenes with (C6H5)2ECl2 where E = Sn, Ge, Si. The Sn and Ge congeners were crystallized, but the conformers that these rings crystallized in, were quite different. As confirmed by Density Functional Theory (DFT) calculations, (C28H22O2S2Sn) assumes a unique crystal structure that leaves more room around the tetrel atom as compared to the crystal structure of the corresponding Ge compound. In the latter, the central cavity is quite open, whereas in the former, one of the methylene groups can fold inwards. Another consequence is the influence on the planes of the aromatic rings flanking the heterocycle. In the Ge case, the benzene ring is folded away from the central cavity, whereas in the Sn case, it is almost parallel to the imaginary axis through the center of the ring. Thermal analysis investigations (TGA and DSC methods) of these eleven-membered rings suggested the loss of a phenyl group in the first decomposition step. The decomposition temperature decreased from the Si containing heterocycle to Ge and was lowest for the Sn containing heterocycle.

The rupture mechanism of rubredoxin is more complex than previously thought.

The surprisingly low rupture force and remarkable mechanical anisotropy of rubredoxin have been known for several years. Exploiting the first combination of steered molecular dynamics and the quantum chemical Judgement of Energy DIstribution (JEDI) analysis, the common belief that hydrogen bonds between neighboring amino acid backbones and the sulfur atoms of the central FeS4 unit in rubredoxin determine the low mechanical resistance of the protein is invalidated. The distribution of strain energy in the central part of rubredoxin is elucidated in real-time with unprecedented detail, giving important insights into the mechanical unfolding pathway of rubredoxin. While structural anisotropy as well as the contribution of angle bendings in the FeS4 unit have a significant influence on the mechanical properties of rubredoxin, these factors are insufficient to explain the experimentally observed low rupture force. Instead, the rupture mechanism of rubredoxin is far more complex than previously thought and requires more than just a hydrogen bond network.

Strain visualization for strained macrocycles.

Strain has a unique and sometimes unpredictable impact on the properties and reactivity of molecules. To thoroughly describe strain in molecules, a computational tool that relates strain energy to reactivity by localizing and quantifying strain was developed. Strain energy is calculated local to every coordinate in the molecule and areas of higher strain are shown experimentally to be more reactive. Not only does this tool directly compare strain energy in parts of the same molecule, but it also computes total strain to give a full picture of molecular strain energy. It is freely available to the public on GitHub under the name StrainViz and much of the workflow is automated to simplify use for non-experts. Unique insight into the reactivity of curved aromatic molecules and strained alkyne bioorthogonal reagents is described within.

Quantum Chemical Modeling of Pressure-Induced Spin Crossover in Octahedral Metal-Ligand Complexes.

Spin state switching on external stimuli is a phenomenon with wide applicability, ranging from molecular electronics to gas activation in nanoporous frameworks. Here, we model the spin crossover as a function of the hydrostatic pressure in octahedrally coordinated transition metal centers by applying a field of effective nuclear forces that compress the molecule towards its centroid. For spin crossover in first-row transition metals coordinated by hydrogen, nitrogen, and carbon monoxide, we find the pressure required for spin transition to be a function of the ligand position in the spectrochemical sequence. While pressures on the order of 1 GPa are required to flip spins in homogeneously ligated octahedral sites, we demonstrate a fivefold decrease in spin transition pressure for the archetypal strong field ligand carbon monoxide in octahedrally coordinated Fe2+ in [Fe(II)(NH3 )5 CO]2+ .

Multiresolution 3D-DenseNet for Chemical Shift Prediction in NMR Crystallography.

We have developed a deep learning algorithm for chemical shift prediction for atoms in molecular crystals that utilizes an atom-centered Gaussian density model for the 3D data representation of a molecule. We define multiple channels that describe different spatial resolutions for each atom type that utilizes cropping, pooling, and concatenation to create a multiresolution 3D-DenseNet architecture (MR-3D-DenseNet). Because the training and testing time scale linearly with the number of samples, the MR-3D-DenseNet can exploit data augmentation that takes into account the property of rotational invariance of the chemical shifts, thereby also increasing the size of the training data set by an order of magnitude without additional cost. We obtain very good agreement for 13C, 15N, and 17O chemical shifts when compared to ab initio quantum chemistry methods, with the highest accuracy found for 1H chemical shifts that is comparable to the error between the ab initio results and experimental measurements. Principal component analysis (PCA) is used to both understand these greatly improved predictions for 1H , as well as indicating that chemical shift prediction for 13C, 15N, and 17O, which have far fewer training environments than the 1H atom type, will improve once more unique training samples are made available to exploit the deep network architecture.

Twist and Return-Induced Ring Strain Triggers Quick Relaxation of a ( Z)-Stabilized Cyclobisazobenzene.

Continuous irradiation of the thermodynamically stable ( Z, Z)-cyclobisazobenzene does not lead to accumulation of a ( Z, E) or ( E, E) isomer as one might expect. Our combined experimental and computational investigation reveals that Z → E photoisomerization still takes place on an ultrafast time scale but induces large ring strain in the macrocycle, which leads to a very fast thermal back-isomerization, preventing photostationary accumulation of ( E)-isomers.

Mechanical Switching of Aromaticity and Homoaromaticity in Molecular Optical Force Sensors for Polymers.

The sensing of mechanical stress in polymers is indispensable for investigating the origin and propagation of cracks that lead to material failure and for designing mechanically responsive polymers. Here the unique approaches of using the force-induced switching of aromaticity and homoaromaticity in molecular optical force sensors for the real-time measurement of mechanical forces acting in stretched polymers are suggested. The mechanical switching of aromaticity in Dewar benzene is an irreversible event, whereas the degree of π-orbital overlap in homoaromatic compounds like homotropylium can be adjusted progressively over a wide range of forces. Using computational methods, it is demonstrated that both approaches lead to significant changes in the visible part of the UV/Vis spectra of the force sensors upon application of weak forces (pN-nN). Polymers that incorporate such molecular force sensors therefore change their color well before material failure occurs.

Quantum Chemical Strain Analysis For Mechanochemical Processes.

The use of mechanical force to initiate a chemical reaction is an efficient alternative to the conventional sources of activation energy, i.e., heat, light, and electricity. Applications of mechanochemistry in academic and industrial laboratories are diverse, ranging from chemical syntheses in ball mills and ultrasound baths to direct activation of covalent bonds using an atomic force microscope. The vectorial nature of force is advantageous because specific covalent bonds can be preconditioned for rupture by selective stretching. However, the influence of mechanical force on single molecules is still not understood at a fundamental level, which limits the applicability of mechanochemistry. As a result, many chemists still resort to rules of thumb when it comes to conducting mechanochemical syntheses. In this Account, we show that comprehension of mechanochemistry at the molecular level can be tremendously advanced by quantum chemistry, in particular by using quantum chemical force analysis tools. One such tool is the JEDI (Judgement of Energy DIstribution) analysis, which provides a convenient approach to analyze the distribution of strain energy in a mechanically deformed molecule. Based on the harmonic approximation, the strain energy contribution is calculated for each bond length, bond angle and dihedral angle, thus providing a comprehensive picture of how force affects molecules. This Account examines the theoretical foundations of quantum chemical force analysis and provides a critical overview of the performance of the JEDI analysis in various mechanochemical applications. We explain in detail how this analysis tool is to be used to identify the "force-bearing scaffold" of a distorted molecule, which allows both the rationalization and the optimization of diverse mechanochemical processes. More precisely, we show that the inclusion of every bond, bending and torsion of a molecule allows a particularly insightful discussion of the distribution of mechanical strain in deformed molecules. We illustrate the usefulness of the JEDI analysis by rationalizing the finding that a knot tremendously weakens a polymer strand via a "choking" motion of the torsions in the curved part of the knot, thus leading to facilitated bond rupture in the immediate vicinity of the knot. Moreover, we demonstrate that the JEDI analysis can be exploited to devise methods for the stabilization of inherently strained molecules. In addition to applications in the electronic ground state, the JEDI analysis can also be used in the electronically excited state to determine the mechanical energy that a molecular photoswitch can release into its environment during photoisomerization. This approach allows the quantification of the mechanical efficiency of a photoswitch, i.e., the part of the energy that becomes available for the motion into a specific direction, which enables us to judge whether a photoswitch is capable of performing a desired switching function.

Force-induced retro-click reaction of triazoles competes with adjacent single-bond rupture.

The highly controversial force-induced cycloreversion of 1,2,3-triazole, its well-known retro-click reaction, is shown to be possible only for 1,5-substituted triazoles, but competes with rupture of an adjacent single-bond. We draw this conclusion from both static and dynamic calculations under external mechanical forces applied to unsubstituted and 1,4- and 1,5-substituted triazoles. The JEDI (Judgement of Energy DIstribution) analysis, a quantum chemical tool quantifying the distribution of strain energy in mechanically deformed molecules, is employed to identify the key factors facilitating the force-induced retro-click reaction in these systems. For 1,4-substituted triazoles it is shown to be impossible, but the parallel alignment of the scissile bond in 1,5-substituted triazoles with the acting force makes it generally feasible. However, the weakness of the carbon-nitrogen bond connecting the triazole ring to the linker prevents selective cycloreversion.

Advances in Quantum Mechanochemistry: Electronic Structure Methods and Force Analysis.

In quantum mechanochemistry, quantum chemical methods are used to describe molecules under the influence of an external force. The calculation of geometries, energies, transition states, reaction rates, and spectroscopic properties of molecules on the force-modified potential energy surfaces is the key to gain an in-depth understanding of mechanochemical processes at the molecular level. In this review, we present recent advances in the field of quantum mechanochemistry and introduce the quantum chemical methods used to calculate the properties of molecules under an external force. We place special emphasis on quantum chemical force analysis tools, which can be used to identify the mechanochemically relevant degrees of freedom in a deformed molecule, and spotlight selected applications of quantum mechanochemical methods to point out their synergistic relationship with experiments.

Can Strained Hydrocarbons Be "Forced" To Be Stable?

Many strained hydrocarbons are prone to isomerization, dimerization, and trimerization under normal laboratory conditions. Here we investigate a method to stabilize angle-strained cycloalkynes by applying a mechanical pulling force to the carbon atoms adjacent to the triple bond, which partially linearizes the C≡C-C bond angles. We discuss various methods of applying such pulling forces, including photoswitches and incorporation into additional strained macrocycles. We use the computational JEDI (Judgement of Energy DIstribution) analysis to quantify the distribution of energy in strained cycloheptyne and judge the change in stability upon application of an external force via isodesmic and homodesmotic reactions. We find that cycloheptyne can indeed be stabilized by external forces. However, the force generated by photoswitches during isomerization is too low to lead to a significant stabilization of the molecule. Hence, stronger forces are needed, which can be achieved by incorporating cycloheptyne into a second strained macrocycle.

Stiff-stilbene photoswitch ruptures bonds not by pulling but by local heating.

The photochemical cis→trans-isomerization of stiff-stilbene (1-(1-indanyliden)indan) was previously used to trigger the ring opening of cyclobutene, i.e. the retro [2+2] cycloaddition leading to butadiene, mechanically. However, the forces generated by stiff-stilbene during photoisomerization are limited, so it is unclear in how far the mechanical properties of stiff-stilbene determine the efficiency of the bond rupture. Here we present a computational study in which we investigate the mechanochemical properties of this reaction. We show that the mechanical work transmitted from stiff-stilbene to cyclobutene is much too low to account for the observed facilitation of the ring opening. Hence, local heating resulting from the absorption of a photon by stiff-stilbene and efficient non-radiative decay are the key elements initiating this reaction.