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Vibronic coupling, or electron-phonon coupling, of naphthalene is calculated. A method of vibronic coupling density analysis, which has been proposed for the vibronic coupling of the Jahn-Teller active modes in a Jahn-Teller molecule, is extended for totally symmetric vibrational modes of a molecule including a non-Jahn-Teller molecule. Contrary to non-totally-symmetric modes, orbital relaxation upon a charge transfer plays a crucial role in the vibronic coupling calculation for the totally symmetric modes. The method is applied for the ground state of the naphthalene anion to compare with that of the benzene anion. The relationship between the vibronic coupling density and a nuclear Fukui function is also discussed.

Expanding the repertoire of electrophiles with unique reactivity features would facilitate the development of covalent inhibitors with desirable reactivity profiles. We herein introduce bicyclo[1.1.0]­butane (BCB) carboxylic amide as a new class of thiol-reactive electrophiles for selective and irreversible inhibition of targeted proteins. We first streamlined the synthetic routes to generate a variety of BCB amides. The strain-driven nucleophilic addition to BCB amides proceeded chemoselectively with cysteine thiols under neutral aqueous conditions, the rate of which was significantly slower than that of acrylamide. This reactivity profile of BCB amide was successfully exploited to develop covalent ligands targeting Bruton’s tyrosine kinase (BTK). By tuning BCB amide reactivity and optimizing its disposition on the ligand, we obtained a selective covalent inhibitor of BTK. The in-gel activity-based protein profiling and mass spectrometry-based chemical proteomics revealed that the selected BCB amide had a higher target selectivity for BTK in human cells than did a Michael acceptor probe. Further chemical proteomic study revealed that BTK probes bearing different classes of electrophiles exhibited distinct off-target profiles. This result suggests that incorporation of BCB amide as a cysteine-directed electrophile could expand the capability to develop covalent inhibitors with the desired proteome reactivity profile.

A method of calculation of vibronic or electron-phonon coupling constant is presented for a Jahn-Teller molecule, cyclopentadienyl radical. It is pointed out that symmetry breaking at degenerate point and violation of Hellmann-Feynman theorem occur in the calculations based on a single Slater determinant. In order to overcome these difficulties, the electronic wave functions are calculated using generalized restricted Hartree-Fock and complete active space self-consistent-field method and the couplings are computed as matrix elements of the electronic operator of the vibronic coupling. Our result agrees well with the experimental and theoretical values. A concept of vibronic coupling density is proposed in order to explain the order of magnitude of the coupling constant from view of the electronic and vibrational structures. It illustrates the local properties of the coupling and enables us to control the interaction. It could open a way to the engineering of vibronic interactions.

Vibronic coupling constants of Jahn-Teller molecules, benzene radical cation and anion, are computed as matrix elements of the electronic part of the vibronic coupling operator using the electronic wave functions calculated by generalized restricted Hartree-Fock and state-averaged complete active space self-consistent-field methods. The calculated vibronic coupling constants for benzene cation agree well with the experimental and theoretical values. Vibronic coupling density analysis, which illustrates the local properties of the coupling, is performed in order to explain the order of magnitude of the coupling constant from view of the electronic and vibrational structures. This analysis reveals that the couplings of the e2g2 and e2g3 modes in which the large displacements locate on C-C bonds are strong in the cation. On the other hand, they are greatly weakened in the anion because of the decrease of electron density in the region of the C-C bonds, which originates from the antibonding nature of the singly occupied molecular orbital of the anion. However, the difference of the electronic structure has a little influence on the vibronic coupling of the e2g4 mode. These results indicate that the vibronic coupling depends not only on the direction of the nuclear displacement but also on the frontier electron density.

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The purpose of this study is the analysis of the influence of anisotropic conductivity on magnetic fields and electric potentials by means of phantom measurements. An artificial rotating current dipole was placed in the middle of an anisotropic skein arrangement in a torso phantom filled with saline solution. The signal strength and the change of the shape of potential and field patterns due to anisotropic volume conduction were investigated. Different directions of the dipole were compared to corresponding orientations of measured fields and potentials (angle difference). For electric and magnetic data, the angle difference between observed signal orientations and true dipole orientations continuously increased with the angle between dipole and anisotropy (up to 80 • ) and then decreased back to zero at their orthogonal orientation. Both signal strengths decreased about 10% with an increasing angle between dipole and anisotropy. While the magnetic field showed a generally stronger shape change, the changed shape of the electric potential showed similarity to an extended source. Our phantom study demonstrated that anisotropic compartments influence directions, amplitudes and shapes of potentials and fields at different degrees. We concluded that anisotropic structures should be considered in volume conductor modelling, when source orientation, extension and strength are of interest.

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