Multiconfigurational photodynamics simulations reveal the mechanism of photodecarbonylations of cyclopropenones in explicit aqueous environments.

Gas-evolving photochemical reactions use light and mild conditions to access strained organic compounds irreversibly. Cyclopropenones are a class of light-responsive molecules used in bioorthogonal photoclick reactions; their excited-state decarbonylation reaction mechanisms are misunderstood due to their ultrafast (<100 femtosecond) lifetimes. We have combined multiconfigurational quantum mechanical (QM) calculations and non-adiabatic molecular dynamics (NAMD) simulations to uncover the excited-state mechanism of cyclopropenone and a photoprotected cyclooctyne-(COT)-precursor in gaseous and explicit aqueous environments. We explore the role of H-bonding with fully quantum mechanical explicitly solvated NAMD simulations for the decarbonylation reaction. The cyclopropenones pass through asynchronous conical intersections and have dynamically concerted photodecarbonylation mechanisms. The COT-precursor has a higher quantum yield of 55% than cyclopropenone (28%) because these trajectories prefer to break a σCC bond to avoid the strained trans-cyclooctene geometries. Our solvated simulations show an increased quantum yield (58%) for the systems studied here.

Design rules for optimization of photophysical and kinetic properties of azoarene photoswitches.

Azoarenes are an important class of molecular photoswitches that often undergo E → Z isomerization with ultraviolet light and have short Z-isomer lifetimes. Azobenzene has been a widely studied photoswitch for decades but can be poorly suited for photopharmacological applications due to its UV-light absorption and short-lived Z-isomer half-life (t1/2). Recently, diazo photoswitches with one or more thiophene rings in place of a phenyl ring have emerged as promising candidates, as they exhibit a stable photostationary state (98% E → Z conversion) and E-isomer absorption (λmax) in the visible light range (405 nm). In this work, we performed density functional theory calculations [PBE0-D3BJ/6-31+G(d,p)] on 26 hemi-azothiophenes, substituted with one phenyl ring and one thiophene ring on the diazo bond. We calculated the E-isomer absorption (λmax) and Z-isomer t1/2 for a set of 26 hemi-azothiophenes. We compared their properties to thiophene-based photoswitches that have been studied previously. We separated the 26 proposed photoswitches into four quadrants based on their λmax and t1/2 relative to past generations of hemi-azothiophene photoswitches. We note 8 hemi-azothiophenes with redshifted λmax and longer t1/2 than previous systems. Our top candidate has λmax and a t1/2 approaching 360 nm and 279 years, respectively. The results here present a pathway towards leveraging and optimizing two properties of photoswitches previously thought to be inversely related.

Multiconfigurational Calculations and Photodynamics Describe Norbornadiene Photochemistry.

Storing solar energy is a vital component of using renewable energy sources to meet the growing demands of the global energy economy. Molecular solar thermal (MOST) energy storage is a promising means to store solar energy with on-demand energy release. The light-induced isomerization reaction of norbornadiene (NBD) to quadricyclane (QC) is of great interest because of the generally high energy storage density (0.97 MJ kg-1) and long thermal reversion lifetime (t1/2,300K = 8346 years). However, the mechanistic details of the ultrafast excited-state [2 + 2]-cycloaddition are largely unknown due to the limitations of experimental techniques in resolving accurate excited-state molecular structures. We now present a full computational study on the excited-state deactivation mechanism of NBD and its dimethyl dicyano derivative (DMDCNBD) in the gas phase. Our multiconfigurational calculations and nonadiabatic molecular dynamics simulations have enumerated the possible pathways with 557 S2 trajectories of NBD for 500 fs and 492 S1 trajectories of DMDCNBD for 800 fs. The simulations predicted the S2 and S1 lifetimes of NBD (62 and 221 fs, respectively) and the S1 lifetime of DMDCNBD (190 fs). The predicted quantum yields of QC and DCQC are 10 and 43%, respectively. Our simulations also show the mechanisms of forming other possible reaction products and their quantum yields.

Virtually the Same? Evaluating the Effectiveness of Remote Undergraduate Research Experiences.

In-person undergraduate research experiences (UREs) promote students' integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration and whether they might perceive doing research less favorably (i.e., not beneficial or too costly). To address these questions, we examined indicators of scientific integration and perceptions of the benefits and costs of doing research among students who participated in remote life science URE programs in Summer 2020. We found that students experienced gains in scientific self-efficacy pre- to post-URE, similar to results reported for in-person UREs. We also found that students experienced gains in scientific identity, graduate and career intentions, and perceptions of the benefits of doing research only if they started their remote UREs at lower levels on these variables. Collectively, students did not change in their perceptions of the costs of doing research despite the challenges of working remotely. Yet students who started with low cost perceptions increased in these perceptions. These findings indicate that remote UREs can support students' self-efficacy development, but may otherwise be limited in their potential to promote scientific integration.

Experimental and theoretical elucidation of SPAAC kinetics for strained alkyne-containing cycloparaphenylenes.

Tuning strained alkyne reactivity via organic synthesis has evolved into a burgeoning field of study largely focused on cyclooctyne, wherein physical organic chemistry helps guide rational molecular design to produce molecules with intriguing properties. Concurrent research in the field of carbon nanomaterials has produced new types of strained alkyne macrocycles, such as cycloparaphenyleneacetylenes, that possess uniquely curved aromatic π systems but hover on the edge of stability. In 2018, we introduced a strained alkyne scaffold that marries the synthetic accessibility and stability of cyclooctyne with the curved π system of carbon nanomaterials. These molecules are strained alkyne-containing cycloparaphenylenes (or [n+1]CPPs), which have been shown to possess size-dependent reactivity as well as the classic characteristics of the unfunctionalized parent CPP, such as a tunable HOMO-LUMO gap and bright fluorescence for large sizes. Herein, we elaborate further on this scaffold, introducing two modifications to the original design and fully characterizing the kinetics of the strain-promoted azide-alkyne cycloaddition (SPAAC) for each [n+1]CPP with a model azide. Additionally, we explain how electronic (the incorporation of fluorine atoms) and strain (a meta linkage which heightens local strain at the alkyne) modulations affect SPAAC reactivity via the distortion-interaction computational model. Altogether, these results indicate that through a modular synthesis and rational chemical design, we have developed a new family of tunable and inherently fluorescent strained alkyne carbon nanomaterials.

Photochemically Mediated Polymerization of Molecular Furan and Pyridine: Synthesis of Nanothreads at Reduced Pressures.

Nanothreads are emerging one-dimensional sp3-hybridized materials with high predicted tensile strength and a tunable band gap. They can be synthesized by compressing aromatic or nonaromatic small molecules to pressures ranging from 15-30 GPa. Recently, new avenues are being sought that reduce the pressure required to afford nanothreads; the focus has been placed on the polymerization of molecules with reduced aromaticity, favorable stacking, and/or the use of higher reaction temperatures. Herein, we report the photochemically mediated polymerization of pyridine and furan aromatic precursors, which achieves nanothread formation at reduced pressures. In the case of pyridine, it was found that a combination of slow compression/decompression with broadband UV light exposure yielded a crystalline product featuring a six-fold diffraction pattern with similar interplanar spacings to previously synthesized pyridine-derived nanothreads at a reduced pressure. When furan is compressed to 8 GPa and exposed to broadband UV light, a crystalline solid is recovered that similarly demonstrates X-ray diffraction with an interplanar spacing akin to that of the high-pressure synthesized furan-derived nanothreads. Our method realizes a 1.9-fold reduction in the maximum pressure required to afford furan-derived nanothreads and a 1.4-fold reduction in pressure required for pyridine-derived nanothreads. Density functional theory and multiconfigurational wavefunction-based computations were used to understand the photochemical activation of furan and subsequent cascade thermal cycloadditions. The reduction of the onset pressure is caused by an initial [4+4] cycloaddition followed by increasingly facile thermal [4+2]-cycloadditions during polymerization.

A Look Inside the Black Box of Machine Learning Photodynamics Simulations.

Photochemical reactions are of great importance in chemistry, biology, and materials science because they take advantage of a renewable energy source, mild reaction conditions, and high atom economy. Light absorption can excite molecules to a higher energy electronic state of the same spin multiplicity. The following nonadiabatic processes induce molecular transformations that afford exotic molecular architectures and high-energy-isomers that are inaccessible by thermal means. Computational simulations now complement time-resolved instrumentation to reveal ultrafast excited-state mechanistic information for photochemical reactions that is essential in disentangling elusive spectroscopic features, excited-state lifetimes, and excited-state mechanistic critical points. Nonadiabatic molecular dynamics (NAMD), powered by surface hopping techniques, is among the most widely applied techniques to model the photochemical reactions of medium-sized molecules. However, the computational efficiency is limited because of the requisite thousands of multiconfigurational quantum-chemical calculations multiplied by hundreds of trajectories. Machine learning (ML) has emerged as a revolutionary force in computational chemistry to predict the outcome of the resource-intensive multiconfigurational calculations on the fly. An ML potential trained with a substantial set of quantum-chemical calculations can predict the energies and forces with errors under chemical accuracy at a negligible cost. The integration of ML potentials in NAMD dramatically extends the maximum simulation time scale by ∼10 000-fold to the nanosecond regime.In this Account, we present a comprehensive demonstration of ML photodynamics simulations and summarize our most recent applications in resolving complex photochemical reactions. First, we address three fundamental components of ML techniques for photodynamics simulations: the quantum-chemical data set, the ML potential, and NAMD. Second, we describe best practices in building training data and our procedure toward training the ML photodynamics model with our recent literature contributions. We introduce a convenient training data generation scheme combining Wigner sampling and geometrical interpolation. It trains reliable and effective ML potentials suitable for subsequent active learning to detect undersampled data. We demonstrate how active learning automatically discovers new mechanistic pathways and reproduces experimental results. We point out that atomic permutation is an essential data augmentation approach to improve the learnability of distance-based molecular descriptors for highly symmetric molecules. Third, we demonstrate the utility of ML-photodynamics by showing the results of ML photodynamics simulations of (1) photo-torquoselective 4π disrotatory electrocyclic ring closing of norbornyl cyclohexadiene, which reveals a thermal conversion from experimentally unobserved intermediates to the reactant in 1 ns; (2) [2 + 2] photocycloaddition of substituted [3]-syn-ladderdienes in competition with 4π and 6π electrocyclic ring-opening reactions, uncovering substituent effects to explain the reported increased quantum yield of substituted cubane precursors; and (3) photochemical 4π disrotatory electrocyclic reactions of fluorobenzenes in nanoseconds with XMS-CASPT2-level training data. We expect this Account to broaden understanding of ML photodynamics and inspire future developments and applications to increasingly large molecules within complex environments on long time scales.

Excited-State Distortions Promote the Photochemical 4π-Electrocyclizations of Fluorobenzenes via Machine Learning Accelerated Photodynamics Simulations.

Benzene fluorination increases chemoselectivities for Dewar-benzenes via 4π-disrotatory electrocyclization. However, the origin of the chemo- and regioselectivities of fluorobenzenes remains unexplained because of the experimental limitations in resolving the excited-state structures on ultrafast timescales. The computational cost of multiconfigurational nonadiabatic molecular dynamics simulations is also currently cost-prohibitive. We now provide high-fidelity structural information and reaction outcome predictions with machine-learning-accelerated photodynamics simulations of a series of fluorobenzenes, C6 F6-n Hn , n=0-3, to study their S1 →S0 decay in 4 ns. We trained neural networks with XMS-CASPT2(6,7)/aug-cc-pVDZ calculations, which reproduced the S1 absorption features with mean absolute errors of 0.04 eV (<2 nm). The predicted nonradiative decay constants for C6 F4 H2 , C6 F6 , C6 F3 H3 , and C6 F5 H are 116, 60, 28, and 12 ps, respectively, in broad qualitative agreement with the experiments. Our calculations show that a pseudo Jahn-Teller distortion of fluorinated benzenes leads to an S1 local-minimum region that extends the excited-state lifetimes of fluorobenzenes. The pseudo Jahn-Teller distortions reduce when fluorination decreases. Our analysis of the S1 dynamics shows that the pseudo-Jahn-Teller distortions promote an excited-state cis-trans isomerization of a πC-C bond. We characterized the surface hopping points from our NAMD simulations and identified instantaneous nuclear momentum as a factor that promotes the electrocyclizations.

Cross-conjugation controls the stabilities and photophysical properties of heteroazoarene photoswitches.

Azoarene photoswitches are versatile molecules that interconvert from their E-isomer to their Z-isomer with light. Azobenzene is a prototypical photoswitch but its derivatives can be poorly suited for in vivo applications such as photopharmacology due to undesired photochemical reactions promoted by ultraviolet light and the relatively short half-life (t1/2) of the Z-isomer (2 days). Experimental and computational studies suggest that these properties (λmax of the E isomer and t1/2 of the Z-isomer) are inversely related. We identified isomeric azobisthiophenes and azobisfurans from a high-throughput screening study of 1540 azoarenes as photoswitch candidates with improved λmax and t1/2 values relative to azobenzene. We used density functional theory to predict the activation free energies and vertical excitation energies of the E- and Z-isomers of 2,2- and 3,3-substituted azobisthiophenes and azobisfurans. The half-lives depend on whether the heterocycles are π-conjugated or cross-conjugated with the diazo π-bond. The 2,2-substituted azoarenes both have t1/2 values on the scale of 1 hour, while the 3,3-analogues have computed half-lives of 40 and 230 years (thiophene and furan, respectively). The 2,2-substituted heteroazoarenes have significantly higher λmax absorptions than their 3,3-substituted analogues: 76 nm for azofuran and 77 nm for azothiophene.

"How Do We Do This at a Distance?!" A Descriptive Study of Remote Undergraduate Research Programs during COVID-19.

The COVID-19 pandemic shut down undergraduate research programs across the United States. A group of 23 colleges, universities, and research institutes hosted remote undergraduate research programs in the life sciences during Summer 2020. Given the unprecedented offering of remote programs, we carried out a study to describe and evaluate them. Using structured templates, we documented how programs were designed and implemented, including who participated. Through focus groups and surveys, we identified programmatic strengths and shortcomings as well as recommendations for improvements from students' perspectives. Strengths included the quality of mentorship, opportunities for learning and professional development, and a feeling of connection with a larger community. Weaknesses included limited cohort building, challenges with insufficient structure, and issues with technology. Although all programs had one or more activities related to diversity, equity, inclusion, and justice, these topics were largely absent from student reports even though programs coincided with a peak in national consciousness about racial inequities and structural racism. Our results provide evidence for designing remote Research Experiences for Undergraduates (REUs) that are experienced favorably by students. Our results also indicate that remote REUs are sufficiently positive to further investigate their affordances and constraints, including the potential to scale up offerings, with minimal concern about disenfranchising students.

A Green Chemistry Approach toward the Stereospecific Synthesis of Densely Functionalized Cyclopropanes via the Solid-State Photodenitrogenation of Crystalline 1-Pyrazolines.

The cyclopropane ring features prominently in active pharmaceuticals, and this has spurred the development of synthetic methodologies that effectively incorporate this highly strained motif into such molecules. As such, elegant solutions to prepare densely functionalized cyclopropanes, particularly ones embedded within the core of complex structures, have become increasingly sought-after. Here we report the stereospecific synthesis of a set of cyclopropanes with vicinal quaternary stereocenters via the solvent-free solid-state photodenitrogenation of crystalline 1-pyrazolines. Density functional theory calculations at the M062X/6-31+G(d,p) level of theory were used to determine the origin of regioselectivity for the synthesis of the 1-pyrazolines; favorable in-phase frontier molecular orbital interactions are responsible for the observation of a single pyrazoline regioisomer. It was also shown that the loss of N2 may take place via a highly selective solid-state thermal reaction. Scalability of the solid-state photoreaction is enabled through aqueous nanocrystalline suspensions, making this method a "greener" alternative to effectively facilitate the construction of cyclopropane-containing molecular scaffolds.

Efficient Discovery of Visible Light-Activated Azoarene Photoswitches with Long Half-Lives Using Active Search.

Photoswitches are molecules that undergo a reversible, structural isomerization after exposure to certain wavelengths of light. The dynamic control offered by molecular photoswitches is favorable for materials chemistry, photopharmacology, and catalysis applications. Ideal photoswitches absorb visible light and have long-lived metastable isomers. We used high-throughput virtual screening to predict the absorption maxima (λmax) of the E-isomer and half-life (t1/2) of the Z-isomer. However, computing the photophysical and kinetic stabilities with density functional theory of each entry of a virtual molecular library containing thousands or millions of molecules is prohibitively time-consuming. We applied active search, a machine-learning technique, to intelligently search a chemical search space of 255 991 photoswitches based on 29 known azoarenes and their derivatives. We iteratively trained the active search algorithm on whether a candidate absorbed visible light (λmax > 450 nm). Active search was found to triple the discovery rate compared to random search. Further, we projected 1962 photoswitches to 2D using the Uniform Manifold Approximation and Projection algorithm and found that λmax depends on the core, which is tunable by substituents. We then incorporated a second stage of screening to predict the stabilities of the Z-isomers for the top candidates of each core. We identified four ideal photoswitches that concurrently satisfy the following criteria: λmax > 450 nm and t1/2 > 2 h.These candidates had λmax and t1/2 range from 465 to 531 nm and hours to days, respectively.

Machine-Learning Photodynamics Simulations Uncover the Role of Substituent Effects on the Photochemical Formation of Cubanes.

Photochemical [2 + 2]-cycloadditions store solar energy in chemical bonds and efficiently access strained organic molecular architectures. Functionalized [3]-ladderdienes undergo [2 + 2]-photocycloadditions to afford cubanes, a class of strained organic molecules. The substituents (e.g., methyl, trifluoromethyl, and cyclopropyl) affect the overall reactivities of these cubane precursors; the yields range from 1 to 48%. However, the origin of these substituent effects on the reactivities and chemoselectivities is not understood. We now integrate single and multireference calculations and machine-learning-accelerated nonadiabatic molecular dynamics (ML-NAMD) to understand how substituents affect the ultrafast dynamics and mechanism of [2 + 2]-photocycloadditions. Steric clashes between substituent groups destabilize the 4π-electrocyclic ring-opening pathway and minimum energy conical intersections by 0.72-1.15 eV and reaction energies by 0.68-2.34 eV. Noncovalent dispersive interactions stabilize the [2 + 2]-photocycloaddition pathway; the conical intersection energies are lower by 0.31-0.85 eV, and the reaction energies are lower by 0.03-0.82 eV. The 2 ps ML-NAMD trajectories reveal that closed-shell repulsions block a 6π-conrotatory electrocyclic ring-opening pathway with increasing steric bulk. Thirty-eight percent of the methyl-substituted [3]-ladderdiene trajectories proceed through the 6π-conrotatory electrocyclic ring-opening, whereas the trifluoromethyl- and cyclopropyl-substituted [3]-ladderdienes prefer the [2 + 2]-photocycloaddition pathways. The predicted cubane yields (H: 0.4% < CH3: 1% < CF3: 14% < cPr: 15%) match the experimental trend; these substituents predistort the reactants to resemble the conical intersection geometries leading to cubanes.

Benchmarking of Density Functionals for Z-Azoarene Half-Lives via Automated Transition State Search.

Molecular photoswitches use light to interconvert from a thermodynamically stable isomer into a metastable isomer. Photoswitches have been used in photopharmacology, catalysis, and molecular solar thermal (MOST) materials because of their spatiotemporal activation. Visible-light-absorbing photoswitches are especially attractive because low-energy light minimizes undesired photochemical reactions and enables biological applications. Ideal photoswitches require well-separated absorption spectra for both isomers and long-lived metastable states. However, predicting thermal half-lives with density functional theory is difficult because it requires locating transition structures and chosing an accurate model chemistry. We now report EZ-TS; by automatically calculating activation energies for the thermal Z → E isomerization. We used 28 density functionals [local spin density approximation, generalized gradient approximation, meta-GGA, hybrid GGA, and hybrid meta-GGA] and five basis sets [6-31G(d), 6-31+G(d,p), 6-311+G(d,p), cc-pVDZ, and aug-cc-pVDZ]. The hybrid GGA functionals performed the best among all tested functionals. We demonstrate that the mean absolute errors of 14 model chemistries approach chemical accuracy.

Automatic discovery of photoisomerization mechanisms with nanosecond machine learning photodynamics simulations.

Photochemical reactions are widely used by academic and industrial researchers to construct complex molecular architectures via mechanisms that often require harsh reaction conditions. Photodynamics simulations provide time-resolved snapshots of molecular excited-state structures required to understand and predict reactivities and chemoselectivities. Molecular excited-states are often nearly degenerate and require computationally intensive multiconfigurational quantum mechanical methods, especially at conical intersections. Non-adiabatic molecular dynamics require thousands of these computations per trajectory, which limits simulations to ∼1 picosecond for most organic photochemical reactions. Westermayr et al. recently introduced a neural-network-based method to accelerate the predictions of electronic properties and pushed the simulation limit to 1 ns for the model system, methylenimmonium cation (CH2NH2 +). We have adapted this methodology to develop the Python-based, Python Rapid Artificial Intelligence Ab Initio Molecular Dynamics (PyRAI2MD) software for the cis-trans isomerization of trans-hexafluoro-2-butene and the 4π-electrocyclic ring-closing of a norbornyl hexacyclodiene. We performed a 10 ns simulation for trans-hexafluoro-2-butene in just 2 days. The same simulation would take approximately 58 years with traditional multiconfigurational photodynamics simulations. We generated training data by combining Wigner sampling, geometrical interpolations, and short-time quantum chemical trajectories to adaptively sample sparse data regions along reaction coordinates. The final data set of the cis-trans isomerization and the 4π-electrocyclic ring-closing model has 6207 and 6267 data points, respectively. The training errors in energy using feedforward neural networks achieved chemical accuracy (0.023-0.032 eV). The neural network photodynamics simulations of trans-hexafluoro-2-butene agree with the quantum chemical calculations showing the formation of the cis-product and reactive carbene intermediate. The neural network trajectories of the norbornyl cyclohexadiene corroborate the low-yielding syn-product, which was absent in the quantum chemical trajectories, and revealed subsequent thermal reactions in 1 ns.

Role of the Perfluoro Effect in the Selective Photochemical Isomerization of Hexafluorobenzene.

Hexafluorobenzene and many of its derivatives exhibit a chemoselective photochemical isomerization, resulting in highly strained, Dewar-type bicyclohexenes. While the changes in absorption and emission associated with benzene hexafluorination have been attributed to the so-called "perfluoro effect", the resulting electronic structure and photochemical reactivity of hexafluorobenzene is still unclear. We now use a combination of ultrafast time-resolved spectroscopy, multiconfigurational computations, and non-adiabatic dynamics simulations to develop a holistic description of the absorption, emission, and photochemical dynamics of the 4π-electrocyclic ring-closing of hexafluorobenzene and the fluorination effect along the reaction coordinate. Our calculations suggest that the electron-withdrawing fluorine substituents induce a vibronic coupling between the lowest-energy 1B2u (ππ*) and 1E1g (πσ*) excited states by selectively stabilizing the σ-type states. The vibronic coupling occurs along vibrational modes of e2u symmetry which distorts the excited-state minimum geometry resulting in the experimentally broad, featureless absorption bands, and a ∼100 nm Stokes shift in fluorescence-in stark contrast to benzene. Finally, the vibronic coupling is shown to simultaneously destabilize the reaction pathway toward hexafluoro-benzvalene and promote molecular vibrations along the 4π ring-closing pathway, resulting in the chemoselectivity for hexafluoro-Dewar-benzene.

A Theoretical Stereoselectivity Model of Photochemical Denitrogenations of Diazoalkanes Toward Strained 1,3-Dihalogenated Bicyclobutanes.

Photochemical reactions exemplify "green" chemistry and are an essential tool for synthesizing highly strained molecules under mild conditions with light. The light-promoted denitrogenation of bicyclic azoalkanes affords functionalized, stereoenriched bicyclo[1.1.0]butanes. These reactions were revisited with multireference calculations and non-adiabatic molecular dynamics (NAMD) simulations to provide a detailed analysis of the photophysics, reactivities, and unexplained stereoselectivity of a series of diazabicyclo[2.1.1]hexenes. We used complete active space self-consistent field (CASSCF) calculations with an (8,8) active space and ANO-S-VDZP basis set; the CASSCF energies were corrected with CASPT2 (8,8)/ANO-S-VDZP. The nature of the electronic excitation is n → π* and ranges from 3.77 to 3.91 eV for the diazabicyclo[2.1.1]hexenes reported here. Minimum energy path calculations showed stepwise C-N bond breaking and led directly to a minimum energy crossing point, corresponding to a stereochemical "double inversion" product. Wigner sampling of diazabicyclo[2.1.1]hexene provided initial conditions for 692 NAMD trajectories. We identified competing complete stereoselective and stereochemical scrambling pathways. The stereoselective pathways feature concerted bicyclobutane inversion and N2 extrusion. The stereochemical scrambling pathways involve N2 extrusion followed by bicyclobutane planarization, leading to stereochemical scrambling. The predicted diastereomeric excess (d.e.) almost exactly matches the experiment (calc.d.e. = 46% vs exp.d.e. = 47%). Our NAMD simulations with 672, 568, and 596 trajectories for 1-F, 1-Cl, and 1-Br predicted a d.e. of 94-97% for the double inversion products. Halogenation significantly perturbs the potential energy surface (PES) toward the retention products due to hyperconjugative interactions. The nC → σ*C-X, X = F, Cl, Br hyperconjugative effect leads to a broader shoulder region on the PES for double inversion.

Mechanochemical synthesis of an elusive fluorinated polyacetylene.

Polymer mechanochemistry has traditionally been employed to study the effects of mechanical force on chemical bonds within a polymer backbone or to generate force-responsive materials. It is under-exploited for the scalable synthesis of wholly new materials by chemically transforming the polymers, especially products inaccessible by other means. Here we utilize polymer mechanochemistry to synthesize a fluorinated polyacetylene, a long-sought-after air-stable polyacetylene that has eluded synthesis by conventional means. We construct the monomer in four chemical steps on gram scale, which involves a rapid incorporation of fluorine atoms in an exotic photochemical cascade whose mechanism and exquisite stereoselectivity were informed by computation. After polymerization, force activation by ultrasonication produces a gold-coloured, semiconducting fluoropolymer. This work demonstrates that polymer mechanochemistry is a valuable synthetic tool for accessing materials on a preparative scale.

Multiconfigurational Calculations and Nonadiabatic Molecular Dynamics Explain Tricyclooctadiene Photochemical Chemoselectivity.

Sunlight is a renewable energy source that can be stored in chemical bonds using photochemical reactions. The synthesis of exotic and strained molecules is especially attractive with photochemical techniques because of the associated efficient and mild reaction conditions. We have understood the photophysics and subsequent photochemistry of a possible cubane precursor, tricyclo[4,2,0,02,5]octa-3,7-diene with complete active space self-consistent field (CASSCF) calculations with an (8,7) active space and the ANO-S-VDZP basis set to. The CASSCF energies were corrected with a second-order perturbative correction CASPT2(8,7)/ANO-S-VDZP. The S0 → S1 vertical excitation energy of 1 is 6.25 eV, which is a π → π* excitation. The minimum energy path from the S1 Franck-Condon point leads to a 4π-disrotatory electrocyclic ring-opening reaction to afford bicyclo[4,2,0]octa-2,4,7-triene. The 2D potential energy surface scan located a rhomboidal S1/S0 minimum energy crossing point connecting 1 and cubane, suggesting that a cycloaddition is theoretically possible. We used the fewest switches surface hopping to study the photodynamics of this cycloaddition: 85% of 1722 trajectories relaxed to eight products; the major products are bicyclo[4,2,0]octa-2,4,7-triene (30%) and cycloocta-1,3,5,7-tetraene (32%). Only 0.4% of trajectories undergo a [2 + 2] cycloaddition to form cubane.

Invasive mechanical ventilation using a bilevel PAP ST device in a healthy swine model.

PURPOSE: The Coronavirus Disease 2019 (COVID-19) pandemic may cause an acute shortage of ventilators. Standard noninvasive bilevel positive airway pressure devices with spontaneous and timed respirations (bilevel PAP ST) could provide invasive ventilation but evidence on their effectiveness in this capacity is limited. We sought to evaluate the ability of bilevel PAP ST to effect gas exchange via invasive ventilation in a healthy swine model. METHODS: Two single limb respiratory circuits with passive filtered exhalation were constructed and evaluated. Next, two bilevel PAP ST devices, designed for sleep laboratory and home use, were tested on an intubated healthy swine model using these circuits. These devices were compared to an anesthesia ventilator. RESULTS: We evaluated respiratory mechanics, minute ventilation, oxygenation, and presence of rebreathing for all of these devices. Both bilevel PAP ST devices were able to control the measured parameters. There were noted differences in performance between the two devices. Despite these differences, both devices provided effective invasive ventilation by controlling minute ventilation and providing adequate oxygenation in the animal model. CONCLUSIONS: Commercially available bilevel PAP ST can provide invasive ventilation with a single limb respiratory circuit and in-line filters to control oxygenation and ventilation without significant rebreathing in a swine model. Further study is needed to evaluate safety and efficacy in clinical disease models. In the setting of a ventilator shortage during the COVID-19 pandemic, and in other resource-constrained situations, these devices may be considered as an effective alternative means for invasive ventilation.