The great diversity and richness of transition metal chemistry, such as the features of an open d-shell, opened a way to numerous areas of scientific research and technological applications. Depending on the nature of the metal and its environment, there are often several energetically accessible spin states, and the progress in accurate theoretical treatment of this complicated phenomenon is presented in this Account. The spin state energetics of a transition metal complex can be predicted theoretically on the basis of density functional theory (DFT) or wave function based methodology, where DFT has advantages since it can be applied routinely to medium-to-large-sized molecules and spin-state consistent density functionals are now available. Additional factors such as the effect of the basis set, thermochemical contributions, solvation, relativity, and dispersion, have been investigated by many researchers, but challenges in unambiguous assignment of spin states still remain. The first DFT studies showed intrinsic spin-state preferences of hybrid functionals for high spin and early generalized gradient approximation functionals for low spin. Progress in the development of density functional approximations (DFAs) then led to a class of specially designed DFAs, such as OPBE, SSB-D, and S12g, and brought a very intriguing and fascinating observation that the spin states of transition metals and the S2 barriers of organic molecules are somehow intimately linked. Among the many noteworthy results that emerged from the search for the appropriate description of the complicated spin state preferences in transition metals, we mainly focused on the examination of the connection between the spin state and the structures or coordination modes of the transition metal complexes. Changes in spin states normally lead only to changes in the metal-ligand bond lengths, but to the best of our knowledge, the dapsox ligand showed the first example of a transition-metal complex where a change in spin state leads also to changes in the coordination, switching between pentagonal-bipyramidal and capped-octahedron. Moreover, we have summarized the results of the thorough study that corrected the experimental assignment of the nature of the recently synthesized Sc adduct of [Fe(O)(TMC)] (TMC = 1,4,8,11-tetramethylcyclam) and firmly established that the Sc-capped iron-oxygen complex corresponds to high-spin Fe. Last, but not least, we have provided deeper insight and rationalization of the observation that unlike in metalloenzymes, where the Fe-oxo is usually observed with high spin, biomimetic Fe-oxo complexes typically have a intermediate spin state. Energy decomposition analyses on the trigonal-bypiramidal (TBP) and octahedral model systems with ammonia ligands have revealed that the interaction energy of the prepared metal ion in the intermediate spin state is much smaller for the TBP structure. This sheds light on the origin of the intermediate spin state of the biomimetic TBP Fe-oxo complexes.

The present study describes the synthesis and anticancer activity of novel octahedral Pt(IV) complexes with cyclohexyl functionalized ethylenediamine-N,N'-diacetate-type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s-cis is the preferred geometry of these Pt(IV) complexes with tetradentate-coordinated (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell-cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt(IV) complexes against various cancer cell lines (IC(50) range: 1.9-8.7 microM) was higher than that of cisplatin (IC(50) range: 10.9-67.0 microM) and proceeded through completely different mechanisms. Cisplatin induced caspase-dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt(IV) complexes caused rapid, caspase-independent, oxidative stress-mediated non-apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.

Density Functional Tight Binding (DFTB) models are two to three orders of magnitude faster than ab initio and Density Functional Theory (DFT) methods and therefore are particularly attractive in applications to large molecules and condensed phase systems. To establish the applicability of DFTB models to general chemical reactions, we conduct benchmark calculations for barrier heights and reaction energetics of organic molecules using existing databases and several new ones compiled in this study. Structures for the transition states and stable species have been fully optimized at the DFTB level, making it possible to characterize the reliability of DFTB models in a more thorough fashion compared to conducting single point energy calculations as done in previous benchmark studies. The encouraging results for the diverse sets of reactions studied here suggest that DFTB models, especially the most recent third-order version (DFTB3/3OB augmented with dispersion correction), in most cases provide satisfactory description of organic chemical reactions with accuracy almost comparable to popular DFT methods with large basis sets, although larger errors are also seen for certain cases. Therefore, DFTB models can be effective for mechanistic analysis (e.g., transition state search) of large (bio)molecules, especially when coupled with single point energy calculations at higher levels of theory.

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The aim of this work was to determine and understand the origin of the electronic properties of Mn(IV) complexes, especially the zero-field splitting (ZFS), through a combined experimental and theoretical investigation on five well-characterized mononuclear octahedral Mn(IV) compounds, with various coordination spheres (N6, N3O3, N2O4 in both trans (trans-N2O4) and cis configurations (cis-N2O4) and O4S2). High-frequency and -field EPR (HFEPR) spectroscopy has been applied to determine the ZFS parameters of two of these compounds, MnL(trans-N2O4) and MnL(O4S2). While at X-band EPR, the axial-component of the ZFS tensor, D, was estimated to be +0.47 cm(-1) for MnL(O4S2), and a D-value of +2.289(5) cm(-1) was determined by HFEPR, which is the largest D-magnitude ever measured for a Mn(IV) complex. A moderate D value of -0.997(6) cm(-1) has been found for MnL(trans-N2O4). Quantum chemical calculations based on two theoretical frameworks (the Density Functional Theory based on a coupled perturbed approach (CP-DFT) and the hybrid Ligand-Field DFT (LF-DFT)) have been performed to define appropriate methodologies to calculate the ZFS tensor for Mn(IV) centers, to predict the orientation of the magnetic axes with respect to the molecular ones, and to define and quantify the physical origin of the different contributions to the ZFS. Except in the case of MnL(trans-N2O4), the experimental and calculated D values are in good agreement, and the sign of D is well predicted, LF-DFT being more satisfactory than CP-DFT. The calculations performed on MnL(cis-N2O4) are consistent with the orientation of the principal anisotropic axis determined by single-crystal EPR, validating the calculated ZFS tensor orientation. The different contributions to D were analyzed demonstrating that the d-d transitions mainly govern D in Mn(IV) ion. However, a deep analysis evidences that many factors enter into the game, explaining why no obvious magnetostructural correlations can be drawn in this series of Mn(IV) complexes.

A general model for the analysis of the Adiabatic Potential Energy Surfaces (APES) of the molecules that are subject to the multimode Jahn-Teller effect is presented. The method utilizes the information obtained by DFT calculations on a distorted stationary point on the APES. The essence of the model is to express the distortion along a model minimal energy path called Intrinsic Distortion Path (IDP), projecting the geometry of the system on the normal modes of the either high-symmetry (HS) or low symmetry (LS) nuclear configuration. This allows us to determine the significance of all of the involved normal modes along a relevant particular path of distortion, and the direct calculation of the vibronic coupling constants. The IDP analysis is illustrated by the discussion of the multimode H ⊗ (g + 2h) JT effect in fullerene cations (C(60)(+)) giving a deep insight into the origin and the mechanism of vibronic coupling in fullerene based molecules.

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Vibronic coupling theory shows that the cause for spontaneous instability in systems presenting a nondegenerate ground state is the so-called pseudo-Jahn-Teller effect, and thus its study can be extremely helpful to understand the structure of many molecules. While this theory, based on the mixing of the ground and excited states with a distortion, has been long studied, there are two obscure points that we try to clarify in the present work. First, the operators involved in both the vibronic and nonvibronic parts of the force constant take only into account electron-nuclear and nuclear-nuclear interactions, apparently leaving electron-electron repulsions and the electron's kinetic energy out of the chemical picture. Second, a fully quantitative computational appraisal of this effect has been up to now problematic. Here, we present a reformulation of the pseudo-Jahn-Teller theory that explicitly shows the contributions of all operators in the molecular Hamiltonian and allows connecting the results obtained with this model to other chemical theories relating electron distribution and geometry. Moreover, we develop a practical approach based on Hartree-Fock and density functional theory that allows quantification of the pseudo-Jahn-Teller effect. We demonstrate the usefulness of our method studying the pyramidal distortion in ammonia and its absence in borane, revealing the strong importance of the kinetic energy of the electrons in the lowest a2″ orbital to trigger this instability. The present tool opens a window for exploring in detail the actual microscopic origin of structural instabilities in molecules and solids.