Kinetically stable high-energy isomers of C14H12 and C12H10N2 derived from cis-stilbene and cis-azobenzene

Following on from our recent enforced geometry optimization (EGO) investigation of isomerization in cis-stilbene (J Comput Chem, in press) we report the discovery of two interesting new, symmetrical “fused sandwich” isomers of both cis-stilbene and the related cis-azobenzene. The isomers were obtained by applying external forces to pairs of carbon atoms from each of the benzene rings in cis-stilbene and cis-azobenzene simultaneously, and are all at least 100 kcal mol-1 higher in energy than the starting material. Each new structure was characterized as a minimum by vibrational analysis. Despite their high energy, all of the new isomers appear to be kinetically stable with respect to rearrangement back to cis-stilbene or cis-azobenzene, respectively

Comment on 'Exploring potential energy surface with external forces'

Recently, a work (Wolinski, K., J. Chem. Theory Comput. 2018, 14, 6306, 10.1021/acs.jctc.8b00885) was published in which the SEGO method (standard and enforced geometry optimization) was proposed to find new minimums on potential energy surfaces. We study this important method from a theoretical point of view. Up to now, the understanding of the proposer does not take into account the barrier breakdown point on a SEGO path being usually half of the path, which is searched for. However, a better understanding of the method allows us to follow along the reaction pathway from a minimum to a saddle point or vice versa. We discuss the well-known two-dimensional MB test surface where we calculate full SEGO pathways. If one has special SEGO curves at hand, one can also detect some weaknesses of the ansatz

Development and Application of Quantum Chemical Methods for the Description of Molecules Under Mechanical Stress

In mechanochemistry, forces are used to initiate chemical reactions. Although mechanochemical reactions have been conducted for millennia, a fundamental understanding of the relevant processes at the molecular level is still unavailable. Nevertheless, mechanochemistry is a lively field with an extraordinarily wide range of applications. Several approaches to apply forces to single molecules are commonly used today. One such approach is Single-Molecule Force Spectroscopy, where forces are transmitted from the cantilever of an Atomic Force Microscope to a macromolecule that is anchored to a glass surface. Moving the cantilever away from the surface exerts a pulling force on the molecule. In another class of mechanochemical experiments, ultrasound baths are used to rupture polymers mechanically or to transduce forces to a mechanically susceptible moiety. This capability of ultrasound baths is due to the collapse of cavitational bubbles in the liquids, which generates tensile forces. Furthermore, ball milling or grinding techniques can be used to crush solids, thereby applying forces to molecules. This procedure can be applied to make and break covalent bonds. Due to the lack of solvent, mechanochemical synthesis in a ball mill shows enormous potential as a sustainable and environment-friendly alternative to thermochemistry. Despite this rich body and long history of experimental mechanochemical procedures, the underlying processes are not well understood at the molecular level. However, such a comprehension is desperately needed for the optimization of mechanochemical syntheses. The use of quantum chemical methods to describe mechanochemical processes, which is called quantum mechanochemistry, has proven to be of tremendous value in understanding mechanochemistry at its most fundamental level. Quantum chemical methods for the description of molecules under external forces afford predictions on force-induced changes in molecular geometry, reactivity and spectroscopic properties. Moreover, force analysis tools are available that can be used to identify the mechanically relevant degrees of freedom in a molecule or its force-bearing scaffold, thereby rationalizing mechanochemical reactivity. During my PhD work, I have developed the JEDI (Judgement of Energy DIstribution) analysis, which is a quantum chemical force analysis tool for the distribution of stress energy in a mechanically deformed molecule. Based on the harmonic approximation, an energy is calculated for each bond, bending and torsion in a molecule, thus allowing the identification of the mechanically most strained regions in a molecule as well as the rationalization of mechanochemical processes. When a molecule is stretched, some internal modes store more energy than others. This leads to particularly large displacements of certain modes and to the preconditioning of selected bonds for rupture. Using the JEDI analysis I investigated the mechanochemical properties of polymer strands that are tangled into knots. In analogy to ropes, polymer strands are weakened by the ubiquitous overhand knot by approximately 50% and the point of bond rupture is located at the “entry” or “exit” of the knot. The JEDI analysis revealed the reason for this behavior. Upon stretching, most stress energy is stored in the torsions of the curved part of the knot and only a remarkably small amount of energy is used to stretch the bonds that ultimately break. This observation leads to the physical picture that the knot “chokes off” the chain in its immediate vicinity. In this process, the torsions act as work funnels that effectively localize the mechanical energy in the knot, thus preconditioning the covalent bonds at its entry and exit for bond rupture. Besides the description of mechanical deformation in the ground state, the JEDI analysis can be used in the electronically excited state to quantify the energy gained by relaxation on the excited state potential energy surface (PES). For this, the harmonic approximation needs to be applicable on the excited state PES of interest. The physical process that is described by the excited state JEDI analysis is fundamentally different from the ground state variant. While in the ground state JEDI analysis the distribution of stress energy in a mechanically deformed molecule is analyzed, i.e. energy is expended for deformation, the excited state JEDI analysis quantifies the energy gained by the relaxation of each internal mode upon relaxation on the excited state PES, i.e. energy becomes available. With the excited state JEDI analysis, the mechanical efficiency of molecular photoswitches can be calculated. The spatial extension of a photoswitch that undergoes, e.g., cis-trans-photoisomerization, changes significantly during this process and forces are exerted on the environment. However, other internal modes of the photoswitch that do not contribute to the change in spatial extension change as a side effect of the relaxation on the excited state PES and a certain amount of energy is wasted on them. This effect limits the mechanical efficiency of photoswitches. Using the excited state JEDI analysis, I investigated the mechanical efficiency of the stiff-stilbene photoswitch, which had been used in an experiment in literature to accelerate the electrocyclic ring opening of cyclobutene by photoisomerization. I found that the mechanical efficiency of stiff-stilbene is much too low to account for the observed enhancement of the reaction. A much more reasonable physical explanation is that excess energy from absorption of a photon is dissipated as heat, which accelerates the rupture of the thermally labile bond in cyclobutene. Furthermore, I used the JEDI analysis to investigate methods for the stabilization of strained hydrocarbons. Angle-strained cycloalkynes with a ring size smaller than eight carbon atoms are highly unstable under normal laboratory conditions, since the C≡C−C bond angles deviate substantially from linearity. Applying an external force in an appropriate direction partially linearizes these bond angles, thus leading to a stabilization of the cycloalkyne. Incorporating cycloheptyne into a macrocycle with stiff-stilbene, however, does not lead to a significant stabilization, since the mechanical efficiency of stiff-stilbene is low. Coupling cycloheptyne to another strained hydrocarbon, on the other hand, stabilizes the molecule tremendously. In particular, cycloheptyne was coupled to a strained cyclophane in a condensed macrocycle and I found that appropriate linking leads to a loss of strain in both hydrocarbons. In addition to the development of the JEDI force analysis tool, I used existing quantum mechanochemical methods to develop molecular force probes. This class of molecules can be incorporated into larger systems like polymers and proteins and can be used to monitor forces acting in different regions of the macromolecules in real-time via force-induced changes in the spectroscopic signals of the force probes. I found that the reduction of point group symmetry upon mechanical deformation of the molecular force probe is a profitable feature, since electronically excited states that are degenerate in the unperturbed state can split up upon application of an external force. This effect can lead to the generation of new peaks in the spectrum, thus allowing the precise identification of the force probe signal. Additionally, I incorporated molecular force probes into the backbone of proteins without disturbing their natural fold. The formation of hydrogen bonds between the force probe and neighboring strands in a β-sheet preserves the secondary and tertiary structure of the protein and allows the identification of the pulling direction. The application of forces along and perpendicular to the backbone yields pronounced and clearly distinguishable signals of the force probes in the infrared and Raman spectra. Advantageously, the intensities of these signals are proportional to the external force at selected points of the spectrum, which makes the molecules “force rulers”. The signals of the force probes can be intensified and shifted to a transparent window in the protein spectrum by isotopic substitution

Photochemistry and photophysics of chemical and biologically relevant systems: mechanisms, dynamics and methodologies

El proyecto presentado en esta Tesis se basa en la aplicación y desarrollo de métodos teóricos y computacionales con el fin de describir la fotoquímica y la fotofísica de compuestos moleculares químicos y de relevancia biológica. Más detalladamente, se lograron los siguientes objetivos: i.Aplicación de la metodología CASPT2//CASSCF al estudio de un modelo de la conformación giro-beta, formado por dos glicinas enlazadas a través de un enlace de hidrógeno. Se consiguieron calcular los caminos de mínima energía encontrados a partir de la irradiación UV que permiten finalmente, la disipación de la energía de excitación como energía vibracional. ii.Aplicación de la metodología CASPT2//CASSCF/AMBER al estudio de mecanismos de fotoestabilidad en la proteína gamma-B-cristalina, que forma (junto con otras proteínas cristalinas) el cristalino del ojo humano. Especialmente, se destaca el papel que puede jugar el elemento denominado "Tyrosine corner", una parte seleccionada de la cadena proteica que permite un giro de aproximadamente 180? a través de un enlace de hidrógeno entre la cadena principal y el grupo lateral de una tirosina. iii.Desarrollo de un método de determinación cuantitativa de la energía de excitación de un cromóforo con diferente sustitución, en el caso de que la sustitución química afecte al cromóforo solo a nivel estructural y no a la naturaleza electrónica del estado excitado considerado. iv.Tratamiento de los efectos del entorno sobre un interruptor molecular inducido por luz, como fuerzas externas que actúan en los dos extremos del cromóforo. En el caso del azobenceno (uno de los interruptores moleculares inducidos por luz más empleado), los isómeros cis y trans muestran una fotosensibilidad considerable respecto a las fuerzas aplicadas, permitiendo la modulación de la longitud de onda del máximo de absorción

Photochemistry and photophysics of chemical and biologically relevant systems: mechanisms, dynamics and methodologies

El proyecto presentado en esta Tesis se basa en la aplicación y desarrollo de métodos teóricos y computacionales con el fin de describir la fotoquímica y la fotofísica de compuestos moleculares químicos y de relevancia biológica. Más detalladamente, se lograron los siguientes objetivos: i.Aplicación de la metodología CASPT2//CASSCF al estudio de un modelo de la conformación giro-beta, formado por dos glicinas enlazadas a través de un enlace de hidrógeno. Se consiguieron calcular los caminos de mínima energía encontrados a partir de la irradiación UV que permiten finalmente, la disipación de la energía de excitación como energía vibracional. ii.Aplicación de la metodología CASPT2//CASSCF/AMBER al estudio de mecanismos de fotoestabilidad en la proteína gamma-B-cristalina, que forma (junto con otras proteínas cristalinas) el cristalino del ojo humano. Especialmente, se destaca el papel que puede jugar el elemento denominado "Tyrosine corner", una parte seleccionada de la cadena proteica que permite un giro de aproximadamente 180? a través de un enlace de hidrógeno entre la cadena principal y el grupo lateral de una tirosina. iii.Desarrollo de un método de determinación cuantitativa de la energía de excitación de un cromóforo con diferente sustitución, en el caso de que la sustitución química afecte al cromóforo solo a nivel estructural y no a la naturaleza electrónica del estado excitado considerado. iv.Tratamiento de los efectos del entorno sobre un interruptor molecular inducido por luz, como fuerzas externas que actúan en los dos extremos del cromóforo. En el caso del azobenceno (uno de los interruptores moleculares inducidos por luz más empleado), los isómeros cis y trans muestran una fotosensibilidad considerable respecto a las fuerzas aplicadas, permitiendo la modulación de la longitud de onda del máximo de absorción

Molecular photoswitches in aqueous environments

Molecular photoswitches enable dynamic control of processes with high spatiotemporal precision, using light as external stimulus, and hence are ideal tools for different research areas spanning from chemical biology to smart materials. Photoswitches are typically organic molecules that feature extended aromatic systems to make them responsive to (visible) light. However, this renders them inherently lipophilic, while water-solubility is of crucial importance to apply photoswitchable organic molecules in biological systems, like in the rapidly emerging field of photopharmacology. Several strategies for solubilizing organic molecules in water are known, but there are not yet clear rules for applying them to photoswitchable molecules. Importantly, rendering photoswitches water-soluble has a serious impact on both their photophysical and biological properties, which must be taken into consideration when designing new systems. Altogether, these aspects pose considerable challenges for successfully applying molecular photoswitches in aqueous systems, and in particular in biologically relevant media. In this review, we focus on fully water-soluble photoswitches, such as those used in biological environments, in both in vitro and in vivo studies. We discuss the design principles and prospects for water-soluble photoswitches to inspire and enable their future applications

Photochemical and photophysical reaction dynamics of chemical and biological systems

Texto en inglés, y resumen y conclusiones en inglés y españolEl proyecto realizado en esta Tesis consiste en el desarrollo y aplicación de metodologías teóricas y computaciones, usadas en la descripción estática y dinámica de procesos fotofísicos y fotoquímicos de compuestos químicos y de interés biológico. Estas metodologías computacionales fueron implementadas aplicando técnicas punteras usadas en el campo de la ciencia de la computación. La presente Tesis se compone de 4 bloques principales. El primero de estos bloques estudia el proceso de transferencia de energía intermolecular, especialmente transferencia de energía triplete. Por su parte, el segundo bloque examina los mecanismos y comportamiento dinámico de dos procesos biológicos fotoinducidos de intereses tecnológico. Mientras el tercer bloque, consiste en el estudio del efecto de fuerzas externas sobre las propiedades espectroscópicas de los sistemas moleculares. Finalmente, el último bloque considera el diseño de dispositivos moleculares que usan cambios conformacionales fotoinducidos en la generación de movimiento controlado. En la sección de transferencia de energía ha sido estudiado el problema de encontrar las principales coordenadas moleculares que modulan de forma eficiente el proceso de transferencia de energía triplete. Así mismo, se llevó a cabo una aproximación dinámica al proceso de transferencia energía triplete a temperatura constante, que completa el estudio estático llevado a cabo en la primera parte de la sección. En la primer parte del segundo bloque, se lleva a cabo la caracterización estática y dinámica de modelos moleculares en el estudio de los fenómenos de quimioluminiscencia y bioluminiscencia. Donde se analiza en detalle el mecanismo de descomposición concertado de la familia de 1,2-dioxetanes. Por su parte, en la segunda sección de este bloque es analizado el efecto del ambiente proteico en la emisión de fluorescencia de la proteína fluorescente IrisFP. En el tercer bloque de la presente Tesis ha sido explorado la respuesta fotodinámica de sistemas moleculares al efecto de una fuerza externa. Discutiendo en detalle el efecto sobre el cambio de la reactividad química a causa de la disrupción del sistema molecular por parte de la fuerza externa. Simultáneamente, se muestran los resultados obtenidos con respecto al cambio en las propiedades espectroscópicas debidos a la fuerza externa y se plantea su posible aprovechamiento en aplicaciones tecnológicas Finalmente en el último bloque del presente trabajo, se expone el diseño y operación de dispositivos moleculares como motores e interruptores controlados mediante ciclos fotoinducidos, controlado la rotación unidireccional en el caso de los motores moleculares a través de puentes de hidrógenos

Photochemical and photophysical reaction dynamics of chemical and biological systems

Texto en inglés, y resumen y conclusiones en inglés y españolEl proyecto realizado en esta Tesis consiste en el desarrollo y aplicación de metodologías teóricas y computaciones, usadas en la descripción estática y dinámica de procesos fotofísicos y fotoquímicos de compuestos químicos y de interés biológico. Estas metodologías computacionales fueron implementadas aplicando técnicas punteras usadas en el campo de la ciencia de la computación. La presente Tesis se compone de 4 bloques principales. El primero de estos bloques estudia el proceso de transferencia de energía intermolecular, especialmente transferencia de energía triplete. Por su parte, el segundo bloque examina los mecanismos y comportamiento dinámico de dos procesos biológicos fotoinducidos de intereses tecnológico. Mientras el tercer bloque, consiste en el estudio del efecto de fuerzas externas sobre las propiedades espectroscópicas de los sistemas moleculares. Finalmente, el último bloque considera el diseño de dispositivos moleculares que usan cambios conformacionales fotoinducidos en la generación de movimiento controlado. En la sección de transferencia de energía ha sido estudiado el problema de encontrar las principales coordenadas moleculares que modulan de forma eficiente el proceso de transferencia de energía triplete. Así mismo, se llevó a cabo una aproximación dinámica al proceso de transferencia energía triplete a temperatura constante, que completa el estudio estático llevado a cabo en la primera parte de la sección. En la primer parte del segundo bloque, se lleva a cabo la caracterización estática y dinámica de modelos moleculares en el estudio de los fenómenos de quimioluminiscencia y bioluminiscencia. Donde se analiza en detalle el mecanismo de descomposición concertado de la familia de 1,2-dioxetanes. Por su parte, en la segunda sección de este bloque es analizado el efecto del ambiente proteico en la emisión de fluorescencia de la proteína fluorescente IrisFP. En el tercer bloque de la presente Tesis ha sido explorado la respuesta fotodinámica de sistemas moleculares al efecto de una fuerza externa. Discutiendo en detalle el efecto sobre el cambio de la reactividad química a causa de la disrupción del sistema molecular por parte de la fuerza externa. Simultáneamente, se muestran los resultados obtenidos con respecto al cambio en las propiedades espectroscópicas debidos a la fuerza externa y se plantea su posible aprovechamiento en aplicaciones tecnológicas Finalmente en el último bloque del presente trabajo, se expone el diseño y operación de dispositivos moleculares como motores e interruptores controlados mediante ciclos fotoinducidos, controlado la rotación unidireccional en el caso de los motores moleculares a través de puentes de hidrógenos

Energy and Charge Transfer in Organic Materials and Its Spectroscopic Signature: An Ab Initio Approach

Energy and charge transfer processes in organic materials have received a tremendous amount of attention in recent years, due to their impact on functionality within a wide range of applications. One prominent example is the field of organic photovoltaics (OPVs), where significant improvements in power conversion efficiency and durability have been achieved over the last decade. Another example is organic scintillators, which have seen a renewed interest due to the constrained supply of helium–3 gas, as well as their ability to discriminate between types of ionizing radiation. Advancement in the design of organic photovoltaic and luminescent materials can be facilitated by molecular level insights into the processes of energy transfer, gained through both experimental observations and theoretical and computational modeling. Thus, this thesis utilizes computational techniques to investigate excited states, and their spectroscopic signatures, in molecular systems that are experimentally relevant for OPVs and organic scintillators. In Chapter II of this thesis, a computational protocol based on density functional theory (DFT) is presented for calculating the dependence of the vibrational frequency of a carbonyl reporter mode on the electronic state of the molecular system, in the context of charge transfer (CT) in organic molecules. This protocol was utilized to study a system consisting of a phenyl–C61–butyric acid methyl ester electron acceptor with a N,N–dimethylaniline donor, in which small frequency shifts of less than 4 cm−1 were observed between the ground state and the CT excited state. A Stark tuning rate of 0.768 cm−1/(MV/cm) was calculated between the vibrational frequency and the electric field. In Chapter III of this thesis, the CT process in a carotenoid–porphyrin–C60 molecular triad was investigated in its two primary conformations (bent/linear) with an explicit tetrahydrofuran solvent via molecular dynamics. Vibrational frequency distributions were calculated for the amide I mode and found to be sensitive to the three electronic states relevant to CT: the Pi–Pi* excited state, the porphyrin-to-C60 CT state, and the carotenoid-to-C60 charge-separated state, with shifts as large as 40–60 cm−1 observed between the CT1 and CT2 states. Rate constants between these states were calculated with a hierarchy of approximations based on the linearized semiclassical method. The CT process was determined to occur via a two-step mechanism, Pi–Pi* -> CT1 -> CT2, where the second step is mediated by the bent-to-linear conformation change. In Chapter IV of this thesis, the role of intersystem crossing (ISC) from S1 to Tn in the pulse-shape discrimination (PSD) ability of single-crystal trans–stilbene was investigated. Time-dependent DFT was used with the newly developed OT– SRSH–PCM method to calculate the excited states, and an equilibrium Fermi’s golden rule approach was employed to calculate transition rate constants. The ISC rates were found to be too slow to compete with prompt fluorescence, and thus do not significantly impact the PSD ability. Deuteration of trans–stilbene was found to have a retarding effect on the ISC rates, with rate constants reduced by as much as 30%. Finally, in Chapter V of this thesis, a novel compute-to-learn pedagogy is presented, in which students design and develop interactive demonstrations of physical chemistry concepts in a peer-led studio environment. The rationale behind the pedagogy and improvements made over the course of three iterations are discussed, as well as an initial assessment of the pedagogy conducted via end-of-semester interviews.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147569/1/klwill_1.pd

New computational algorithms and molecular structure studies

Ph.DDOCTOR OF PHILOSOPH