On the applicability of the HSAB principle through the use of improved computational schemes for chemical hardness evaluation

Finite difference schemes, named Compact Finite Difference Schemes with Spectral-like Resolution, have been used for a less crude approximation of the analytical hardness definition as the second-order derivative of the energy with respect to the electron number. The improved computational schemes, at different levels of theory, have been used to calculate global hardness values of some probe bases, traditionally classified as hard and soft on the basis of their chemical behavior, and to investigate the quantitative applicability of the HSAB principle. Exchange acid-base reactions have been used to test the HSAB principle assuming the reaction energies as a measure of the stabilization of product adducts.     

Local HSAB principle in the conjugate addition of p‐substituted thiophenols to cyclohexenone

In the formation of new bonds through the Michel‐type addition of thiolates to a α,β‐conjugate system, it is observed that the reaction takes place faster if the thio donor compound contains an electron‐rich group or the enone acceptor is highly electron deficient. In contrast, the hard–soft acid–base (HSAB) principle predicts that this reaction is favored when a soft–soft interaction between the reactants takes place. Taking into account that softness is related to a barely electronegative atom of high polarizability, we consider it of interest to analyze the effect of charge transfer of a p‐substituent on the softness of sulfur in thiophenols, as well as its impact in the conjugate addition to 2‐cyclohexen‐1‐one. Experiments‐in‐competition, net charge of X‐groups at the p‐position of the aromatic ring, the global and local softness at sulfur, and the electrophilicity, obtained by density functional theory (DFT), led to the observation that the reaction is faster for electron attractor thiophenols. The softness at sulfur increases by delocalization of charge through the aromatic ring. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Validity limits of the superposition principle when applied to reactions the kinetics of which is diffusion controlled

The superposition principle which is commonly used to solve the Smoluchowsky equation can be proved to be unreliable by elementary calculations applied to a particular example. But the practical kinetic consequences are small and usually hidden whithin experimental errors.

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Reaction of dithio-substituted cinnamyllithium with carbonyl compounds: a test of the HSAB principle

By mediation of BF₃.Et₂O, dithio-substituted cinnamyllithium 2 reacted predominantly at the α-site with carbonyl compounds. No selectivity was found when the reaction was performed in the absence of BF₃.Et₂O.     

Theoretical study of dopamine. Application of the HSAB principle to the study of drug–receptor interactions

We present a theoretical conformational study of neutral and N-protonated form of dopamine in which we relate its pharmacological activity to the chemical hardness. We have found that the neutral form presents small fluctuations in the energy and the chemical hardness with the conformational variables, whereas the N-protonated form shows significant changes in both properties. An important result is that the Principle of Maximum Hardness is satisfied. The trans coplanar rotamers are postulated as the pharmacophoric conformation(s) because these rotamers show minimal chemical hardness. In addition, we have calculated the hardness of a model of the anionic binding site of the dopamine receptor, which is formed by a formate ion and two benzenes. We have compared the hardness calculated for this model with the hardness of the isolated formate anion, and found that the hardness of the base in the binding site is lower than that of the isolated formate group. Also, it is found that the hardness of the anionic binding site model is similar to that of both trans coplanar rotamers of protonated dopamine, in agreement with the Hard and Soft Acid and Base Principle.     

Electronic aspect of the HSAB principle (hard and soft acids and bases)

Using the quantum mechanical SCF MO LCAO and SCF X-SW methods, we have shown the effect of the hard and soft acids and bases principle in a new aspect: Inversion of the metal halides series BX₃ and AlX₃ (X=F, Cl, Br) on going from N- to P- and from O- to S-containing bases. We have analyzed the electronic nature of the differences in the systems NH₃, PH₃ and OH₂, SH₂ responsible for the inversion of the acid series.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 22, No. 1, pp. 75–78, January–February, 1986.     

HSAB principle and desulphuration reaction during ionic coordination polymerization of thiiranes [1]

Desulphuration of trimethylthiirane (TMT), catalyzed by anionic and cationic catalysts for thiirane polymerization, has been studied. The possibility of obtaining polymers having mono-, di- and trisulphide bonds during TMT polymerization by typical cationic catalysts has been shown. Some peculiarities of the desulphuration reaction during the polymerization of thiiranes by ionic catalysts have been found. Differences in their catalytic action, shown by the formation of different quantities of both disulphide SSbonds in polymer chain and alkene, are discussed from the point of view of HSAB principle and symbiotic effect of ligands at the counterion. It is shown that desulphuration reactions during the cationic and anionic polymerization of thiiranes have a similar electronic nature, consisting of increase of coordinative state and the activation of the acceptor orbital of the thiirane sulphur atom. The nucleophilic attack by thiirane (during cationic polymerization) or growing thiolate-ion (during anionic polymerization) on the electrophilic sulphur atom of thiiranium intermediates

respectively, is accompanied by concerted fragmentation of these intermediates, giving the alkene and disulphide fragment. Possible mechanisms have been suggested for thiirane desulphuration and SSbond formation in products of the ionic polymerization of thiiranes. HSAB principle proved to be very useful for discussion of experimental results and other aspects of thiirane polymerization.     

Farewell to the HSAB treatment of ambident reactivity

The concept of hard and soft acids and bases (HSAB) proved to be useful for rationalizing stability constants of metal complexes. Its application to organic reactions, particularly ambident reactivity, has led to exotic blossoms. By attempting to rationalize all the observed regioselectivities by favorable soft-soft and hard-hard as well as unfavorable hard-soft interactions, older treatments of ambident reactivity, which correctly differentiated between thermodynamic and kinetic control as well as between different coordination states of ionic substrates, have been replaced. By ignoring conflicting experimental results and even referring to untraceable experimental data, the HSAB treatment of ambident reactivity has gained undeserved popularity. In this Review we demonstrate that the HSAB as well as the related Klopman-Salem model do not even correctly predict the behavior of the prototypes of ambident nucleophiles and, therefore, are rather misleading instead of useful guides. An alternative treatment of ambident reactivity based on Marcus theory will be presented.     

Maximum entropy principle applied to semiflexible ring polymers

Based on the success of the maximum entropy principle (MEP) in the study of semiflexible treelike polymers [M. Dolgushev and A. Blumen, J. Chem. Phys. 131, 044905 (2009)], it is of much interest to establish MEP's potential for general semiflexible polymers which contain loops. Here, we embark on this endeavor by considering discrete semiflexible polymer rings in a Rouse-type scheme. Now, for treelike polymers a beads-and-bonds (i.e., a discrete) picture is essential for an easy inclusion of branching points. Moreover, one may envisage (similar to our former work [M. Dolgushev and A. Blumen, J. Chem. Phys. 131, 044905 (2009)]) to impose for each angle between two bonds a distinct stiffness condition. Working in this way leads already for a polymer ring to a complicated problem. Hence, we follow a reduced variational approach as applied earlier to polymer chains, in which a single Lagrange multiplier is used for each set of identical conditions imposed on topologically equivalent bonds and bonds' orientations. In this way, we obtain for the discrete ring an analytically closed form which involves Chebyshev polynomials. This expression turns out to lead to a series of solutions: Apart from the regular solution, several other solutions appear. One may be tempted to discard the other solutions, since for them the potential energy matrix is not positive definite. A more careful analysis based on topological features suggests, however, that such solutions can be assigned to rings displaying knots. Monte Carlo simulations which take excluded volume interactions into account agree with our interpretation.     

The complementarity principle in chemical reactions. modifications of the indolinedione-indole rearrangement and enamine synthesis

The experimental discovery of a significant modification of a chemical reaction has always been considered a noteworthy achievement. As shown below, four modifications of the indolinedione-indole rearrangement and three modifications of the synthesis of β-diketones provide evidence for the usefulness of the complementarity principle [1] for the discovery of such specific reactions.     

Quantum chemical methods and their applications to chemical reactions

This review is concerned with the impact of quantum chemistry on chemical reactions. Starting from the mid-sixties it focusses on those developments which have enabled us to predict essential features of simple chemical reactions. Thus model theories and computational methods are presented which provide the tools for these predictions. Then procedures to characterize potential surfaces and search methods for reaction paths are described. It is also attempted to relate these features to the terminology of the experimentalist. Finally a systematic survey of the main types of reaction (rearrangement, addition, elimination, substitution) is given.     

Fractal to classical crossover of chemical reactions

Computer simulations on binary reactions of random walkers (A + A → A) on two- and three-dimensional percolation clusters bear out the recent superuniversality conjecture (integrated reaction rate α t²¹³). Moreover, the fractal-to-euclidean crossover (t²¹³ to t dependence) parallels that of the single walker.     

Mass spectrometry-based metabolomics applied to the chemical safety of food

Mass spectrometry (MS)-based metabolomics is emerging as an important field of research in many scientific areas, including chemical safety of food. A particular strength of this approach is its potential to reveal some physiological effects induced by complex mixtures of chemicals present at trace concentrations. The limitations of other analytical approaches currently employed to detect low-dose and mixture effects of chemicals make detection very problematic. Besides this basic technical challenge, numerous analytical choices have to be made at each step of a metabolomics study, and each step can have a direct impact on the final results obtained and their interpretation (i.e. sample preparation, sample introduction, ionization, signal acquisition, data processing, and data analysis). As the application of metabolomics to chemical analysis of food is still in its infancy, no consensus has yet been reached on defining many of these important parameters. In this context, the aim of the present study is to review all these aspects of MS-based approaches to metabolomics, and to give a comprehensive, critical overview of the current state of the art, possible pitfalls, and future challenges and trends linked to this emerging field.     

Enantioselective reactions catalyzed by synthetic enzymes. A model for chemical evolution

Polyleucines of various lengths act as enantioselective catalysts in the aldol condensation between cyclohexanone and various aromatic aldehydes. Polyleucine and other polyamino acids behave as synthetic enzymes in the epoxidation of chalcone and other electron-deficient alkenes. Both reactions are of considerable prebiotic significance.