Four modifications of the Jahn-Teller effects. The problem of observables: spin-orbit interaction, tunneling splitting, and orientational polarization of solids.

In a semi-review paper, we first show that Landau's fundamental idea of the origin of spontaneous symmetry breaking (SSB) in atomic matter due to electronic degeneracy, termed the Jahn-Teller effect (JTE) and further developed into the pseudo-JTE (PJTE), was appended recently with two more modifications, the hidden JTE (h-JTE) and hidden PJTE (h-PJTE). All four versions of JTEs are defined in the adiabatic approximation by their adiabatic potential energy surfaces (APES), which possess a common feature - the lack of a minimum in the high-symmetry configuration, thus confirming (and extending) the Landau idea of SSB. However, although serving as a qualitative indication of the SSB and consequent possible (virtual) properties of the system, the APES by themselves are not experimentally observable directly, and this important feature of JTEs is often ignored. Taking spin-orbit interaction as an example, we show that just perturbation of the APES does not reveal its observable reduction by the JTE, which emerges only after solving the Schrödinger equation with this APES. Following the multi-minimum nature of the latter, this leads to tunneling splitting of the vibrational states in the minima wells or over-the-barrier (hindered) rotations, resulting in novel properties, one of them being the reduction of the spin-orbit coupling. We demonstrate the methodology of solving such problems by using the example of electric field polarization of the BaTiO3 crystal, which leads to a novel effect: orientational polarization of solids.

Sub-lattice of Jahn-Teller centers in hexaferrite crystal.

A novel type of sub-lattice of the Jahn-Teller (JT) centers was arranged in Ti-doped barium hexaferrite BaFe12O19. In the un-doped crystal all iron ions, sitting in five different crystallographic positions, are Fe3+ in the high-spin configuration (S = 5/2) and have a non-degenerate ground state. We show that the electron-donor Ti substitution converts the ions to Fe2+ predominantly in tetrahedral coordination, resulting in doubly-degenerate states subject to the [Formula: see text] problem of the JT effect. The arranged JT complexes, Fe2+O4, their adiabatic potential energy, non-linear and quantum dynamics, have been studied by means of ultrasound and terahertz-infrared spectroscopies. The JT complexes are sensitive to external stress and applied magnetic field. For that reason, the properties of the doped crystal can be controlled by the amount and state of the JT complexes.

Deviations from Born-Oppenheimer theory in structural chemistry: Jahn-Teller, pseudo Jahn-Teller, and hidden pseudo Jahn-Teller effects in C3H3 and C3H3(-).

The electronic structure and vibronic coupling in two similar molecular systems, radical C3H3 and anion C3H3(-), in ground and excited states, are investigated in detail to show how their equilibrium structures, in deviation from the Born-Oppenheimer approximation, originate from the vibronic mixing of at least two electronic states, producing the Jahn-Teller (JT), pseudo JT (PJT), and hidden PJT effects. Starting with the high-symmetry geometry D3h of C3H3, we evaluated its 2-fold degenerate ground electronic state (2)E″ and two lowest excited states (2)A1' and (2)E' and found that all of them contribute to the distortion of the ground state via the JT vibronic coupling problem E″ ⊗ e' and two PJT problems (E″ + A1') ⊗ e″ and (E″ + E') ⊗ (a2″ + e″); all the three active normal modes e'(1335 cm(-1)), e″(1030 cm(-1)), and a2″(778 cm(-1)) are imaginary, meaning that all the three vibronic couplings are sufficiently strong to cause instability, albeit in different directions. The first of them, the ground state JT effect, enhances one of the C-C bonds (toward an ethylenic form with C2v symmetry), while the two PJT effects produce, respectively, cis (a2″ toward C3v symmetry) and trans (e″) puckering of the hydrogen atoms. As a result, C3H3 has two coexisting equilibrium configurations with different geometry. In the C3H3(-) anion, the ground electronic state in D3h symmetry is an orbitally nondegenerate spin triplet (3)A2' with a group of close in energy singlet and triplet excited states in the order of (1)A1', (3)A1″, (1)E″, (3)E″, and (1)E'. This shows that two PJT couplings, ((3)A2' + (3)A1″) ⊗ a2″ and ((3)A2' + (3)E″) ⊗ e″, may influence the geometry of the equilibrium structure in the (3)A2' state. Indeed, both vibrational modes, a2″(1034 cm(-1)) and e″(1284 cm(-1)), are imaginary in this state. Similar to the radical case, they produce, respectively, cis (a2″) and trans (e″) puckering of the hydrogen atoms, but no e' distortion of the basic C3 triangle; the equilibrium configuration with Cs symmetry occurs along the stronger e″ distortions. Another higher-in-energy triplet-state minimum with C2v symmetry emerges as a result of a strong JTE in the excited (3)E″ electronic state. In addition to these APES minima with spin-triplet electronic states, the system has a coexisting minimum with a spin-singlet electronic state, which is shown to be due to the hidden PJT effect that couples two singlet excited states. The two lowest equilibrium configurations of the C3H3(-) anion with different geometry and spin realize a (common to all electronic e(2) configurations) magnetic and structural bistability accompanied by a spin crossover. Some general spectroscopic consequences are also noted. As a whole, this article is intended to demonstrate the efficiency of the vibronic coupling approach in rationalizing the origin of complicated structural features of molecular systems as due to a combination of nonadiabatic JT effects.

Ultrasonic evaluation of the Jahn-Teller effect parameters. Application to ZnSe:Cr2+.

A method is constructed that uses ultrasonic experiments to evaluate the parameters of the Jahn-Teller (JT) effect in impurity centers in crystals. The method is based on measurements of temperature dependent attenuation and phase velocity and does not require assumptions about mechanisms of relaxation. The results are illustrated by measurements performed on the impurity system ZnSe:Cr(2+), in which the Cr(2+) ion has a threefold degenerate T term in the ground state, subject to the [Formula: see text] JT problem. Ultrasound propagation anomalies show that the main JT distortions of the tetrahedral environment of the Cr(2+) ion are of tetragonal E type and hence the lowest branch of the adiabatic potential energy surface (APES) is formed in accordance with the [Formula: see text] problem. With dopant concentration 3.8 × 10(18) cm(-3) the modulus of the constant of linear vibronic coupling to tetragonal E type vibrations is determined by two independent experiments: |F(E)| = 5.49 × 10(-5) dyn revealed from attenuation measurements, while a slightly different value |F(E)| = 5.57 × 10(-5) dyn emerges from phase velocity measurements. Contributions of other active vibronic modes to the elastic modulus C(l) = (C(11) + C(12) + 2C(44))/2 are analyzed and it is shown that the influence of the totally symmetric mode is negligible. Using additional information about this system obtained from independent sources, we also estimated the primary force constant in the E direction (K(E)≈(1.4-4.2) × 10(4) dyn cm(-1)) and orthorhombic and trigonal saddle points of the APES in the five-dimensional space of the tetragonal and trigonal coordinates, their stabilization energies being E(JT)(O)≈81-450 cm(-1) and E(JT)(T)≈48-417 cm(-1), respectively (the variations of the K(E), E(JT)(O) and E(JT)(T) values are due to different literature data for E(JT)(E)). With these data the APES of the JT linear [Formula: see text] problem for the Cr(2+) ion in the ZnSe:Cr(2+) system is revealed.

Pharmacophore identification and quantitative bioactivity prediction using the electron-conformational method.

A review of the Electron-Conformational (EC) method of pharmacophore (Pha) identification and quantitative bioactivity prediction in drug design and toxicology is presented, which includes the latest advances and improvements of the method as a whole and details of its realization with illustration of results. In the first part devoted to Pha identification the data of conformational analysis and electronic structure calculation of each of the molecules in the training set are used to construct EC matrices of congruity (ECMC) that include atomic interaction indices as diagonal elements, and bond orders and interatomic distances as off-diagonal elements. Multiple comparisons of the ECMC's of the active compounds between themselves and with those of inactive compounds allows one to separate a relatively small number of matrix elements that within certain tolerances are common to all the ECMC's of the active compounds, while not present in the same combination in the inactive compounds. This is the EC submatrix of activity that represent the Pha, while the tolerances characterize the Pha flexibilities. Distinguished from QSAR approaches, the Pha is obtained here by computational (non-statistical) methods only. The second part of the problem, quantitative activity prediction, is based on using the Pha flexibilities together with the anti-Pha shielding and other auxiliary groups influence in a parameterization and regression analysis procedure that allows for quantitative prediction. An original approach is suggested that side steps the multi-conformational implications. This post-Pha problem is similar to a QSAR approach with special physically transparent descriptors that allow one to avoid chance correlations in the regression procedure. Illustration of the method is given for several drug design problems in which, where sufficiently accurate experimental data are available, the identification of the Pha as a necessary condition of activity is almost 100% correct, while quantitative activity prediction is near to the accuracy of the experimental data, 80% - 90%.

Improved electron-conformational method of pharmacophore identification and bioactivity prediction. Application to angiotensin converting enzyme inhibitors.

The electron-conformational (EC) method of pharmacophore (Pha) identification and bioactivity prediction, suggested earlier, is given here two major improvements. First, an atomic index of orbital and charge controlled interaction is introduced to better represent the ligand (substrate) in its interaction with the bioreceptor. Second, the multiconformational problem is considered in view of ligand-receptor binding states, resulting in essential simplification of the expression of bioactivity. The details of the improved EC method are demonstrated in application to the problem of angiotensin converting enzyme (ACE) inhibitors. The Pha of the latter is identified by separation of the heavily populated conformations of the chosen 51 compounds (the training set), calculation of the electronic structure, construction of their EC matrixes of congruity, and processing of the latter in comparison with the activities to reveal a common submatrix of all the active only compounds that describes the Pha. The latter contains three oxygen atoms plus a fourth atom X = S, N, O at certain interatomic distances and with restricted electronic parameters (within assumed tolerances), the position of the atom X being more changeable from one active compound to another. For quantitative prediction of the bioactivity, an expression is deduced which takes into account the duly parametrized influence of auxiliary groups (AG) which, being positioned outside the Pha, either diminish the activity (antipharmacophore shielding) or enhance it. It is shown that in case of many conformations of the same compound only one of them, that of the lowest energy which has the Pha, should be parametrized. The 15 parameters chosen to represent the AG in case of ACE inhibitors are weighted by variational (adjustable) coefficients which are determined from a regression treatment of the calculated versus known activities in the training set. Then the formulas with known coefficients are used to validate the method by calculating the bioactivity of other compounds not used in the training set. The prediction of the activity proved to be more than 90% (within experimental error and available compounds) qualitatively (yes, no) and about 60%-70% quantitatively.

An electron-conformational method of identification of pharmacophore and anti-pharmacophore shielding: application to rice blast activity.

In extension and improvement of previous results, a novel method is worked out for pharmacophore identification and activity prediction in structure-activity relationships. In this method, as in our previous works, each molecular system (conformation) of the training set is described by a matrix with both electron structural parameters (atomic charges, bond orders, etc.) and interatomic distances as matrix elements. This description includes a rather full geometry of charge and/or reactivity distribution thus providing a much better representation of the molecular properties in their interaction with the target. By multiple comparison of these matrices for the active and inactive compounds of the training set, a relatively small number of matrix elements are revealed that are common for all the active compounds and are not present in the same combination in the inactive ones. In this way a set of electronic and geometry parameters is obtained that characterize the pharmacophore (Pha). A major improvement of this scheme is reached by introducing the anti-pharmacophore shielding (APS) and a proper treatment of the conformational problem. The APS is defined as molecular groups and competing charges outside the basic skeleton (the Pha plus the inert neighbor atoms that do not affect the activity) that hinder the proper docking of the Pha with the bioreceptor thus diminishing (partially or completely) the activity. A simple empirical formula is derived to estimate the relative contribution of APS numerically. Two main issues are most affected by the APS: (1) the procedure of Pha identification is essentially simplified because only a small number of molecular systems with the highest activity and simplest structures (systems without APS) should be tried for this purpose; (2) with the APS known numerically, we can make a quantitative (or semiquantitative) prediction of relative activities. The contributions of different conformations (of the same molecular system) that possess the Pha and different APS is taken into account by means of a Boltzmann distribution at given temperatures. Applied to an example, rice blast activity, this approach proved to be rather robust and efficient. In validation of the method, the screening of 39 new compounds yields approximately 100% (within experimental error) prediction probability of the activity qualitatively (yes, no), and with r2 = 0.66 quantitatively.

A novel electron-conformational approach to molecular modeling for QSAR by identification of pharmacophore and anti-pharmacophore shielding.

Abstract A novel method of pharmacophore identification and activity prediction in structure-activity (structure-property) relationships is worked out as an essential extension and improvement of previous publications. In this method each conformation of the molecular systems in the training set of the SAR problem is presented by both electronic structure and geometry parameters arranged in a matrix form. Multiple comparisons of these matrices for the active and inactive compounds allows one to separate a smaller number of matrix elements that are common for all the active compounds and are not present in the same arrangement in the inactive ones. This submatrix of activity represents the pharmacophore (Pha). By introducing the Anti-Pharmacophore Shielding (APS) defined as molecular groups and competing charges outside the Pha that hinder the proper docking of the Pha with the bioreceptor, the procedure of Pha identification is essentially reduced to the treatment of a smaller number of simplest in structure most active and inactive compounds. A simple empirical scheme is suggested to estimate the APS numerically, while the contributions of different conformations of the same compound are taken into account by means of Boltzmann distribution. This enables us to make approximate quantitative predictions of activities. In application to rice blast activity we reached an approximately 100% (within experimental error) prediction probability of the activity qualitatively (yes, no), and with r (2) = 70% quantitatively.

[Electron factors in peroxidase properties and the mechanism of activation of oxygen with heme-containing proteins]. / Elektronnye faktory v svoistvakh peroksidazy i mekhanizm aktivatsii kisloroda gemsoderzhashchimi belkami.

A quantum-chemical calculation was carried out for the electronic structure of coordination compounds of general formula FeP (L1) (L2) (P-porphine; L1-imidazole or imidazolate; L2-CO, O2 or is absent), modelling the active sites of number of hemoproteins. The elucidation of electronic structures of the complexes under consideration explains the similar shapes and band positions of optical absorption and magnetic circular dichroism spectra of oxy- and carboxycomplexes of myoglobin, hemoglobin, and peroxidase. It is shown that the Coulomb repulsion between electrons of the lone pair of the imidazolate distal nitrogen leads to the transfer of the electronic density from this ligand to the dioxygen. This results in the strong dioxygen activation leading, in particular, to the high catalytical activity of peroxidase.

Structural and electronic origin of meat odour of organic hetero-atomic compounds.

By means of the electron-topologic approach suggested earlier, the structural and electronic features favouring meat odour occurrence are evaluated using 77 organic compounds with known odorant properties as a basis for primary logico-structural analysis. A general fragment of the type XH2 (where X = S, O, N is a hetero-atom) with a certain electronic structure and conformational property is shown to be responsible for the meat odour. The results obtained allow for a prognosis of odorant compounds and their purposeful synthesis.

[Structural traits of the antioxidant and fungicidal activity of steroid glycosides]. / Strukturnye priznaki antioksidantnoi i fungitsidnoi aktivnosti steroidnykh glikozidov.

To investigate the origin of antioxidant and antifungal properties of steroid glycosides (SG), a logico-structural analysis of the structure-activity relationships has been performed for 70 compounds using a set of computer programs STRAC. The following structural features responsible for antioxidant activity are revealed: 1) furostanol type of aglycon; 2) the presence of more than 4 branched monosaccharides in the carbohydrate chain; 3) the presence of glucose at C26 and OH-groups in the genin part of SG. Most characteristic for antifungal activity is the fragment genin-C3-Gal-Glc-Glc-Rha..., as well as the spirostanol type of aglycon. The computer analysis provided the basis for predicting a type of biological activity for 12 new compounds of the SG class.