Theoretical Thermochemistry for Organic Molecules: Development of the Generalized Connectivity-Based Hierarchy

Abstract

A generalized, unique thermochemical hierarchy applicable for all closed shell organic molecules is developed in this paper. In this chemically intuitive, structure-based approach, the connectivity of the atoms in an organic molecule is used to construct our hierarchy called "connectivity-based hierarchy" (CBH). The hierarchy has several rungs and ascending up the hierarchy increasingly balances the reaction energy. It requires no prior knowledge of the types of molecules and hybridizations for the appropriate balancing of the bond types and the bonding environments of the atoms. The rungs can be generated by an automated computer program for any closed shell organic molecule, and the first three rungs generate the simplest reactions for the widely used isodesmic, hypohomodesmotic, and hyperhomodesmotic schemes. The generated reaction schemes are unique for each rung and are derived in a simpler manner than previous approaches, avoiding potential errors. This work also suggests that for closed shell organic molecules, the previously well-studied homodesmotic scheme does not have a fundamental structure-based origin. In a preliminary application of CBH, density functional theory has been used to calculate accurate enthalpies of formation for a test set of 20 organic molecules. The performance of the hierarchy suggests that it will be useful to predict accurate thermodynamic properties of larger organic molecules.

The Successful Merger of Theoretical Thermochemistry with Fragment-Based Methods in Quantum Chemistry

“…(iv) Perform an MP2 calculation on the full molecule, M, to obtain E M MP2 . Only a single MP2 calculation To test the accuracy of CBH to get extrapolated CCSD(T) energies, we included all the varied 27 nonaromatic molecules from our earlier test set for obtaining accurate enthalpies of formation 36,37,39 and added glucose (ring and open forms) and alanine dipeptide. 39 The 30 molecule test we assembled ( Figure 6) was further divided into test set A and test set B.…”

“…As previously illustrated in detail in ref 36, it is useful to envision the different levels of CBH as the rungs of a ladder, such that ascending the rungs of the hierarchy increasingly preserves the chemical environment (i.e., a better matching of the bond-types and hybridization-types is automatically achieved) of a molecule ( Figure 1). We call these different rungs CBH-0, CBH-1, CBH-2, CBH-3, etc.…”

“…This is easily and elegantly extended for all CBH rungs by noticing a recursive relationship between the products at one rung, and the reactants at the next rung ( Figure 3), as documented in our earlier work. 36 The recursive relationship naturally arises since we increasingly preserve the chemical environment of larger parts of a molecule on going up in the hierarchy.…”

“…The CBH schemes for cyclohexanone ( Figure 5), demonstrate these features (recursion, terminal moiety cancellation, and counting twice at the branch point). More examples explaining all these facets in great detail can be found in ref 36.…”

Molecular electrostatic potentials by systematic molecular fragmentation

“…The later involves breaking the molecule into fragments, evaluating the energy or property of the relatively small fragments, and then recombining the fragment energies or properties to estimate the total molecular values. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Some methods have been applied to very large molecules. 23 The computational time for these fragmentation methods scales linearly with the size of the molecule.…”