Search

The Fukui function is a frequently used DFT concept in the description of a system’s regioselective preferences to undergo electrophilic, nucleophilic, or radical attacks. Until now, this function has usually been evaluated using finite difference approximations. The first paper in this series proposed a method for obtaining the Fukui function by a direct calculation of the functional derivative of the chemical potential with respect to the external potential. This paper extends the method to condensed Fukui functions and applies it to an extensive testing set of molecules. Results are promising, which demonstrates the usefulness of the new formalism. [ABSTRACT FROM AUTHOR]

In an earlier publication, we suggested that the faster radiodefluorination kinetics of no-carrier-added ( S)-3-(2-[18F]fluoromethyl-phenyl)-2-amino-propionic acid (2-[18F]FMLP), as compared to 4-[18F]-fluoromethyl- l-phenylalanine (4-[18F]FMLP), was caused by an intramolecular interaction between the CH2F group on the 2-position of the phenyl ring and the ammonium group of the amino acid. As the presence of nonradioactive ( S)-3-(2-fluoromethyl-phenyl)-2-amino-propionic acid (2FMLP) in a concentration up from 10−6 mol/L reduces considerably the defluorination rate due to the formation of dimers, conventional experimental methods, like spectroscopy, cannot be performed for the study of the hydrolysis in no-carrier-added conditions occurring at a concentration range of about 5.0 10−10 mol/L. In the present study, we aim to provide a proof that supports aforementioned hypothesis as well as to establish a kinetic model and to put forward accompanying rate equations for this hydrolysis reaction by combining ab initio quantum chemical calculations and kinetic data. The calculations of the optimized geometries and the corresponding energies of the reactants involved in the hydrolysis of 2-[18F]FMLP and 4-[18F]FMLP were performed at the DFT[B3LYP/6-31++G**] level of theory. Interpretation of these data reveals that in 2-[18F]FMLP three intramolecular hydrogen bond interactions can be identified that are not present in 4-[18F]FMLP. The most important interaction is the one between the amino acid ammonium group and the benzylic fluorine atom, rendering the rupture of the CF bond much more favorable. These findings align with the experimental data and enabled us to put forward the rate expressions that define the unexpected pseudo-zero-order defluorination reaction of 2-[18F]FMLP at neutral pH. This study also proves that in the development of [18F]-benzylfluoride containing tracers present-day quantum chemical calculations are capable of predicting intramolecular interactions, affecting their reactivity toward hydrolysis at the no-carrier-added level. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 705-711, 2012 [ABSTRACT FROM AUTHOR]

The extent of relativistic effects on the Fukui function, which describes local reactivity trends within conceptual density functional theory (DFT), and frontier orbital densities has been analysed on the basis of three benchmark molecules containing the heavy elements: Au, Pb, and Bi. Various approximate relativistic approaches have been tested and compared with the four-component fully relativistic reference. Scalar relativistic effects, as described by the scalar zeroth-order regular approximation methodology and effective core potential calculations, already provide a large part of the relativistic corrections. Inclusion of spin-orbit coupling effects improves the results, especially for the heavy p-block compounds. We thus expect that future conceptual DFT-based reactivity studies on heavy-element molecules can rely on one of the approximate relativistic methodologies. [ABSTRACT FROM AUTHOR]

Abstract: This letter is concerned with the calculation and interpretation of the atom-condensed linear response kernel as defined within conceptual density functional theory. An easily applicable and accurate methodology following from second order perturbation theory is used to analyse a series of cyclohexane and benzene derivatives. We show that the variation of the condensed linear response matrix elements with internuclear distance provides a means to differentiate between inductive, resonance and hyperconjugation effects and conclude that this quantity measures the extent of electron delocalisation. [ABSTRACT FROM AUTHOR]

In this contribution, we have investigated the performance of the initial hardness response, a reactivity index from conceptual DFT, in the prediction of the allowed or forbidden character of a series of sigmatropic hydrogen shifts, which are traditionally explained using the famous Woodward-Hoffmann rules for pericyclic reactions. Previously, it was observed that this quantity can be linked to the activation hardness of a chemical reaction and, in this case, thus to the aromaticity of the transition state in these kinds of reactions. It is shown, both by considering approximate reaction coordinates and intrinsic reaction coordinates that the allowed mode of the sigmatropic rearrangement corresponds to the largest value of the initial hardness response, in agreement with earlier work on cycloadditions and electrocyclizations. [ABSTRACT FROM AUTHOR]