Addy Pross

The Reactivity—Selectivity Principle and its Mechanistic Applications

Publisher Summary This chapter focuses on the status of reactivity–selectivity relationships by exploring the basis and variety of such relationships, and outlines the limitations of this principle. A qualitative statement of reactivity–selectivity principle is that highly reactive species are unselective in their choice of reactants compared to stable and, therefore, unreactive species. In a particular reaction series, an increase in the reactivity of one of the reactants results in a corresponding decrease in the selectivity of that species. In certain mechanistic areas, for example electrophilic substitution and carbene chemistry, mechanistic information can be derived by the reactivity–selectivity principle, which serves as a key probe into the stability and the structure of highly active species. The observation of a reactivity–selectivity relationship for a given reaction series suggests a certain uniformity in mechanism; a sudden break or the total failure to obtain such a relationship suggests the opposite. In view of the basic nature of the assumptions on which the reactivity–selectivity principle is based, reactivity–selectivity relationships serve as a probe into some of the fundamental tenets of theoretical chemistry. Some limitations of this principle are that it only applies to processes which obey a rate- equilibrium relationship; it only operates for relatively simple processes; reactions in which solvation factors contribute substantially to the overall energy change may also bring about a breakdown in the principle. The utility of the reactivity–selectivity principle is illustrated for a number of diverse areas of mechanistic interest.

A General Approach to Organic Reactivity: The Configuration Mixing Model

Publisher Summary The aim of this chapter is to present in some detail a simple, qualitative framework for understanding the factors which go into the creation of a reaction profile. Because the question raised is so fundamental —“What determines the barrier in any chemical reaction?”—the model encompasses within its single structure reactions as different as electron-transfer reactions. It brings under one roof both thermal and photochemical processes. The theory termed as the “configuration mixing (CM) model,” or when valence-bond configurations are solely utilized, the “valence-bond configuration mixing (VBCM) model” has been applied over recent years to many of these mentioned reaction types. In view of the fundamental role played by quantum theory in modern chemistry, it is not surprising that the theoretical basis of the CM model goes back to the earliest days of quantum chemistry. In fact, the basic concept of CM theory may be considered a theoretical precursor of resonance theory. The chapter concludes that the notion that a molecule “hesitates” between different structures, borrows its characteristics, and finally adopts a structure that is somewhat intermediate between them, is central to understanding “electronic behavior.” It is from this single yet powerful principle that CM theory borrows its utility and generality.

Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics

A sudden transition in a system from an inanimate state to the living state—defined on the basis of present day living organisms—would constitute a highly unlikely event hardly predictable from physical laws. From this uncontroversial idea, a self-consistent representation of the origin of life process is built up, which is based on the possibility of a series of intermediate stages. This approach requires a particular kind of stability for these stages—dynamic kinetic stability (DKS)—which is not usually observed in regular chemistry, and which is reflected in the persistence of entities capable of self-reproduction. The necessary connection of this kinetic behaviour with far-from-equilibrium thermodynamic conditions is emphasized and this leads to an evolutionary view for the origin of life in which multiplying entities must be associated with the dissipation of free energy. Any kind of entity involved in this process has to pay the energetic cost of irreversibility, but, by doing so, the contingent emergence of new functions is made feasible. The consequences of these views on the studies of processes by which life can emerge are inferred.

Toward a general theory of evolution: Extending Darwinian theory to inanimate matter

Though Darwinian theory dramatically revolutionized biological understanding, its strictly biological focus has resulted in a widening conceptual gulf between the biological and physical sciences. In this paper we strive to extend and reformulate Darwinian theory in physicochemical terms so it can accommodate both animate and inanimate systems, thereby helping to bridge this scientific divide. The extended formulation is based on the recently proposed concept of dynamic kinetic stability and data from the newly emerging area of systems chemistry. The analysis leads us to conclude that abiogenesis and evolution, rather than manifesting two discrete stages in the emergence of complex life, actually constitute one single physicochemical process. Based on that proposed unification, the extended theory offers some additional insights into lifes unique characteristics, as well as added means for addressing the three central questions of biology: what is life, how did it emerge, and how would one make it?

The origin of life: what we know, what we can know and what we will never know

The origin of life (OOL) problem remains one of the more challenging scientific questions of all time. In this essay, we propose that following recent experimental and theoretical advances in systems chemistry, the underlying principle governing the emergence of life on the Earth can in its broadest sense be specified, and may be stated as follows: all stable (persistent) replicating systems will tend to evolve over time towards systems of greater stability. The stability kind referred to, however, is dynamic kinetic stability, and quite distinct from the traditional thermodynamic stability which conventionally dominates physical and chemical thinking. Significantly, that stability kind is generally found to be enhanced by increasing complexification, since added features in the replicating system that improve replication efficiency will be reproduced, thereby offering an explanation for the emergence of lifes extraordinary complexity. On the basis of that simple principle, a fundamental reassessment of the underlying chemistry–biology relationship is possible, one with broad ramifications. In the context of the OOL question, this novel perspective can assist in clarifying central ahistoric aspects of abiogenesis, as opposed to the many historic aspects that have probably been forever lost in the mists of time.

On the emergence of biological complexity: life as a kinetic state of matter.

A kinetic model that attempts to further clarify the nature of biological complexification is presented. Its essence: reactions of replicating systems and those of regular chemical systems follow different selection rules leading to different patterns of chemical behavior. For regular chemical systems selection is fundamentally thermodynamic, whereas for replicating chemical systems selection is effectively kinetic. Building on an extension of the kinetic stability concept it is shown that complex replicators tend to be kinetically more stable than simple ones, leading to an on-going process of kinetically-directed complexification. The high kinetic stability of simple replicating assemblies such as phages, compared to the low kinetic stability of the assembly components, illustrates the complexification principle. The analysis suggests that living systems constitute a kinetic state of matter, as opposed to the traditional thermodynamic states that dominate the inanimate world, and reaffirms our view that life is a particular manifestation of replicative chemistry.

The mechanism for nucleophilic substitution of α-carbonyl derivatives. Application of the valence-bond configuration mixing model

The valence-bond configuration mixing model (VBCM) is applied to the nucleophilic substitution reactions of α-carbonyl derivatives. The model appears to resolve satisfactorily a number of features of these reactions that current mechanisms have not dealt with. These include: (i) the dependence of the rate-enhancing efect of the carbonyl upon the nucleophilic strength of the entering group, (ii) the unusually large Hammett ρ value for the reaction of PhCOCH2Br with substituted pyridines, and (iii) the mechanism by which the rate-enhancing effect of the carbonyl group is transmitted to the reaction centre.

Is the most stable gas-phase isomer of the benzenium cation a face-protonated π-complex?

The recent suggestion, based on gas-phase experimental data, that the most stable isomer of protonated benzene has a face-protonated π-complex structure is not supported by our detailed computations which indicate that the π-complex is a second-order saddle point on the potential energy surface, lying 199 kJ mo–1 higher in energy than the well-established C2vσ-protonated structure.

A high-level ab initio investigation of identity and nonidentity gas-phase SN2 reactions of halide ions with halophosphines

Abstract The high-level ab initio procedures G2(+) and G2(+)[ECP(S)]have been employed in an investigation of S N 2 reactions at neutral tri-coordinated phosphorus. The process has been modeled by identity and nonidentity substitution reactions involving a series of halophosphines PH 2 X and halide ions. We find that the reaction proceeds without an intervening barrier by way of a tetra-coordinated phosphorus anion intermediate (XPH 2 Y − ). This contrasts with the corresponding process for the carbon and nitrogen analogues, where the tetra-coordinated species is a transition structure. The threshold for inversion of the phosphorus intermediate is found to lie below the reaction energy in the cases where F − is the leaving group, but above it in all the other cases. The S N 2 reaction will therefore lead to racemization when F − is expelled. In the other cases, it is possible in principle that the reaction can be controlled to proceed with inversion, but because of the relatively low barriers for inversion, this is not a very likely outcome. We predict that the tetra-coordinated intermediate should be detectable, if not isolable, and that the S N 2 reaction at neutral tri-coordinated phosphorus is exothermic when the reactant halide ion is more electronegative than the product halide ion, and endothermic when the reverse applies.

ON THE CHEMICAL NATURE AND ORIGIN OF TELEONOMY

The physico-chemical characterization of a teleonomic event and the nature of the physico-chemical process by which teleonomic systems could emerge from non-teleonomic systems are addressed in this paper. It is proposed that teleonomic events are those whose primary directive is discerned to be non-thermodynamic, while regular (non-teleonomic) events are those whose primary directive is the traditional thermodynamic one. For the archetypal teleonomic event, cell multiplication, the non-thermodynamic directive can be identified as being a kinetic directive. It is concluded, therefore, that the process of emergence, whereby non-teleonomic replicating chemical systems were transformed into teleonomic ones, involved a switch in the primacy of thermodynamic and kinetic directives. It is proposed that the step where that transformation took place was the one in which some pre-metabolic replicating system acquired an energy-gathering capability, thereby becoming metabolic. Such a transformation was itself kinetically directed given that metabolic replicators tend to be kinetically more stable than non-metabolic ones. The analysis builds on our previous work that considers living systems to be a kinetic state of matteras opposed to the traditional thermodynamic states that dominate the inanimate world