Structural Ontology and Chemical Epistemology The case of

Structural Ontology and Chemical Epistemology: The case of the p-complex Dr. Eamonn F. Healy Professor of Chemistry St. Edward’s University Austin, Tx.

“I find troublesome Dewar’s statement that our formulation of the ethylene bromonium ion involves a ring but his doesn’t. All that is meant by a three membered ring is a triangular arrangement of 3 atoms. ” – Saul Winstein (1950) “The exclusive anionoid reactivity of olefines can then be explained if the intermediate ‘cyclic’ cation is in fact a p complex in which a bromous cation is linked to the p electrons of the C=C bond…. the corresponding reaction with an anion is impossible since ethylene has no vacant electron orbital of low energy and cannot therefore act as an electron acceptor without actual fission of the p bond” – Michael J. S. Dewar (1949)

where

Structural Ontology: The Molecular bond “…Dewar’s contribution represented an outstanding leap of the imagination. ” - D. Michael Mingos (2001) “…Chatt got credit for the idea by showing that I was right and he was wrong!” Michael Dewar (1988)

Chemical Epistemology: The Potential Energy Surface

Organic mechanism: The Constructivist approach Unified Mechanistic Concept of Electrophilic Aromatic Nitration: Convergence of Computational Results and Experimental Data, Olah et al JACS (2009)

Organic mechanism: The Principled approach Sir Robert Robinson Sir Christopher K. Ingold (1924) (1926) “. . . these ideas constituted, in the writer's opinion, his most important contribution to knowledge. . . “ - Robinson (1976) “They represent, in my opinion, a very fine effort, especially on theoretical side, and theory is certainly one of organic chemistry and not of aromatic substitution only. ” - Ingold (1926) “The new work made it inescapably clear that the old order in organic chemistry was changing, the art of the subject diminishing, its science increasing: no longer could one just mix things: sophistication in physical chemistry was the base from which all chemists, including the organic chemist, must start. ” - Chem. Rev. (1934)

J. Chem. Soc. , (1925) J. Chem. Soc. , (1926) J. Chem. Soc. , (1927) J. Chem. Soc. , (1926)

Organic mechanism: Principled vs Constructivist

Direct Observation of the Wheland Intermediate in Electrophilic Aromatic Substitution – Jay K. Kochi JACS (2000) Using electrophilic carriers EY where Y=OH, OAc, NO 3, Cl and Py as a source of electrophilic E+, electron donor acceptor (EDA) complexes are formed with a variety of electron-rich aromatic hydrocarbons, followed by thermal or photochemical activation to yield aromatic substitution: Irradiating these EDA complexes at the wavelength associated with the charge-transfer band using picosecond time-resolved spectroscopy to follow the result Kochi has identified the following mechanism:

Transient absorption spectra obtained at 0. 5, 1. 5, 4. 2, and 18 ms (top to bottom) following the charge -transfer excitation of themesitylene/NO+ EDA complex in dichloromethane at -60°C with a 10 -ns laser pulse at 355 nm. The spectra consist of the two overlapping absorption bands of mesitylene cation radical (centered at 470 nm) and nitrosomesitylenium cation (centered at 430 nm).

Charge Transfer Mechanism for Electrophilic Aromatic Nitration and Nitrosation via the Convergence of ab Initio Molecular-Orbital and Marcus-Hush Theories with Experiments - Head-Gordon and Kochi JACS (2003)

Structure and Dynamics of Reactive Intermediates in Reaction Mechanisms. s– and p-Complexes in Electrophilic Aromatic Substitutions– Jay K Kochi JOC (2000) Superposition of the X-ray structures of hexamethylbenzene complexes with various electrophiles showing the continuous transition from the heptamethylbenzenium s-complex to the hexamethylbenzene/nitrosonium p-complex depending on the electrophile.

Electron Transfer in Electrophilic Aromatic Nitration and Nitrosation: Computational Evidence for the Marcus Inverted Region - Yirong Mo JOTC (2013)

“Well I tend not to be interested in the more abstruse aspects of quantum mechanics. I take a sort of Bridgmanian attitude toward them. Bridgman with his ideas about operational significance of everything would say that a question that does not have operational significance, that does not lead to an experiment of some sort or an observation, isn’t significant. I never have been bothered by the detailed or penetrating discussions about interpretation of quantum mechanics. ” - Interview of Linus Pauling by John L. Heilbron (1964) ‘f 2 may be taken as the measure of density of an “electron gas” representing the average electron distribution over a comparatively long period’, and since this distribution represents all we can know about the electron, ‘the failure to localize the electrons more exactly is of little practical importance’ “Modern chemistry and molecular biology are the products of quantum mechanics…The concept of the - Electronic Theory of Organic chemical bond is the most valuable concept in Chemistry (1949) chemistry. Its development over the past 150 years has been one of the greatest triumphs of the human intellect. ” - J. Chem. Ed. (1992) The theory of resonance was not only 'claimed to be' a direct consequence of quantum mechanics, it was a direct consequence of quantum mechanics. - Proc. R. Soc. Lond. (1977) “Ingold spent so much time (1932 -1946) on this project, he was a victim of the preoccupation that theoretical physics was going to solve the problems of chemistry, including that of predicting chemical reactivity. He was fascinated by seeing how the transition state concept had been transformed by Eyring into an “activated complex”. He hypothesized then that one might use the electronic spectra of polyatomic molecules, hoping that one of the electronically excited states was identical to the reactive state. Actually, the spectroscopic studies on molecules such as acetylene and formaldehyde had shown that in the excited state these molecules have different geometries from those in the ground state. If one could identify the molecular geometry of benzene and determine the energy associated with its reactive state, it would become possible to discuss quantitatively the aromatic reactivity problem. ” - C. K. INGOLD AND THE ACTIVATED COMPLEX GEOMETRY Giorgio Montaudo (2010)

Structural Ontology: Visualizing the molecular wavefunction Atoms in Molecules from the exact one-electron wavefunction - Geoffrey Hunter Can. J. Chem. (1996) Given the experimental electron density, wavefunction: , for an N-electron system, the satisfies the one-electron Schrödinger equation: where ER is the total electronic energy Ur, R is the effective potential for the motion of the single electron, Since: then and Therefore a semi-log plot of the experimental electron density gradient, , will display the topology of the one-electron wavefunction.

Structural Ontology: The s-complex and the molecular bond Studies of [(C 5 Me 5)Os(L)H 2(H 2)+] Complexes. - Christopher. L. Gross Organometallics (2007) H H M

A 1. 654 H 1 1. 632 1. 654 Hb 1. 015 Ha H 2

A 1. 716 1. 645 1. 649 H 1 H 2 Hb 1. 074 Ha C 1. 605 H 1 1. 631 H 2 1. 5 51 1. 600 Hb 1. 306 Ha

as compared to C 1. 605 H 1 1. 5 51 1. 631 H 2 1. 600 Hb 1. 306 Ha

Synthesis, Structural Diversity, Dynamics, and Acidity of [MH 3(PR 3)4]+ (M = Fe, Ru, Os; R= Me, Et) Complexes Dmitry G. Gusev JACS (1997) H 1 1. 865 6 1. 52 1. 561 H 3 H 2 “There is a remarkable asymmetry of bonding in the Fe(H 2) demonstrated by all three (calculated and experimental) structures. This was explained invoking a weak attractive interaction between the cis H and H 2 ligands (between H 1 and H 2 in the Figure). The theoretical report on [Fe. H(H 2)(PH 3)4]+ also mentions that those hydrogens in the positions of H 3 and H 2 look as if they retained “memory” on their chemical origin, i. e. , that one of H 3 appears as a proton coordinating onto a classical hydride−iron bond. This structural feature however still remains speculative” Dmitry G. Gusev et al (1997)

Atoms in Molecules H 1 1. 865 6 1. 52 1. 561 H 3 H 2

“In addition, models involve commitments which are properly described as involving more than belief in the model as a good com puting device. Potential energy surfaces are a prime example. Yes, such surfaces allow us to calculate. They are also entities which we cannot observe in principle. But that does not entail that they are not physi cally significant. Energy minima and slopes are real…In short, I believe we must endorse models as a locus of epistemo logical and ontological commitment. ” - (1996) A final characteristic feature of many constructive theories is the presence of entities not given by the fundamental theory. Critics can defend the use of constructive theories because they give information about these explanatory entities. The potential energy surface is such an entity. The surface was (and is) inaccessible to experiment. - (2000)

The Electronic Theory of Organic Chemistry A Quantum Mechanical Discussion of Orientation of Substituents in Aromatic Molecules G. W. Wheland, Linus Pauling J. Am. Chem. Soc. , 1935, 57 (11), pp 2086– 2095 CCCLXXXVIII. —The nature of the alternating effect in carbon chains. Part XXII. An attempt further to define the probable mechanism of orientation in aromatic substitution Christopher Kelk Ingold, Florence Ruth Shaw J. Chem. Soc. , 1927, 2918 -2926

Learning to Predict Chemical Reactions – Pierre Baldi J. Chem. Inf. Model (2011) “While mechanistic reaction representations are approximations quite far from the Schrodinger equation, we expect them to be closer to the underlying reality and therefore more useful than overall [rules based molecular graph] transformations. Furthermore, we expect them also to be easier to predict than overall transformations due to their more elementary nature. In combination, these arguments suggest that working with mechanistic steps may facilitate the application of statistical machine learning approaches as well as their capability to generalize. “