Chemistry 125: Lecture 35 Understanding Molecular Structure and Energy through Standard Bonds Although molecular mechanics is imperfect, it is useful for discussing molecular structure and energy in terms of standard covalent bonds. Analysis of the Cambridge Structural Database shows that predicting bond distances to within 1% required detailed categorization of bond types. Early attempts to predict heats of combustion in terms of composition proved adequate for physiology, but not for chemistry. Group- or bond-additivity schemes are useful for understanding heats of formation, especially when corrected for strain. Heat of atomization is the natural target for bond-energy schemes, but experimental measurement requires spectroscopic determination of the heat of atomization of elements in their standard states. Synchronize when the speaker finishes saying “…and the answer is yes.” Synchrony can be adjusted by using the pause(||) and run(>) controls. For copyright notice see final page of this file

Are They “True”? YES They are indispensable. Are Molecular Mechanics Programs Useful? NO

C Br van der Waals Radius Br Br Contact

Br neighbor positions from many crystals (CSD) Nyburg & Faerman, Acta Crystallographica B41, (1985) C Br To balance attractive and repulsive forces between neighboring molecules, the closest atoms must be "too" close. Bromine atoms seem not to be spherical! Molecular Mechanics Programs Assume They Are! ? Br Br Contact

Angiostatin anti-cancer drug “We optimized kringle 1 with the AM1 method using Gaussian 03. Plasminogen kringle 1 contains 1200 atoms, which are made up of 642 heavy atoms and 578 hydrogen atoms. The job takes about 650 optimization steps starting from the MM+ geometry.” M. J. Frisch, Gaussian, Inc., 2003 largest molecule calculated by quantum mechanics Despite its problems MM is necessary for complex structures

Is the standard Structural Model realistic in geometric detail? X-Ray Diffraction

Cambridge Structural Database Total X-Ray Structures Year Atoms per Structure >500,000 predicted by ,572,792 atomic positions Jan >40,000,000 BONDS

CSD1

Number of Mean Bond Lengths Tabulated. (specialized because of influence of neighbors on precise bond distance) 175 CC 97 CN 119 CO 119 different types of CO bonds 27 different types of C sp 3 -C sp 3 bonds

CSD1 mean high 1/4 median low 1/4 # obs std dev 3 C* means C bearing C,H only C# means any Csp 3 crowding stretches bond even moreso short long R 2 CH CR 3 R 2 CH CHR 2 R 3 C CR 3 RCH 2 CH 3 R 2 CH CH 3 R 3 CH CH 3 ~1%

C-C bond lengths single 1.53 Å double 1.32 triple 1.18 aromatic 1.38 (one-and-a-half bonds) single: sp 3 -sp sp 2 -sp

N to C aromatic Bond Lengths N PlanarN Pyramidal N N + _ poor  overlap  Twist Bimodal ? N :

How Complex Must a Model be to Predict Useful Structures? To get standard deviations in bond distance of 0.015Å (~1%) the Cambridge crew defined: 682 kinds of bonds altogether 175 different kinds of CC bonds (differing in multiplicity, hybridization, attached groups, rings, etc.) 97 different types of CN bonds 119 different types of CO bonds

We want to understand all “Stuff” Its Properties & Transformations Key: Structure & Energy Bonds?

How Standard are Bond Energies? Obviously there will be correction for conformation and strain, but is there an underlying energy for composition or constitution?

Adolph Oppenheim: On the Relationship of Heat of Combustion with the Constitution of Substances Ludimar Hermann: On the Regularity and Calculation of Heat of Combustion of Organic Compounds. By a frequently expressed need of physiology to be able to calculate heats of combustion, I have been led to study the current situation…

 H Combustion by C / H Content? Substance Carbons atoms/mole Hydrogens atoms/mole Theory  H combust kcal/mole Error kcal/mole Error % Graphite [1] Hydrogen c-Hexane c-Hexanol Ethene Glucose Not too bad for fuel purposes, especially if one were to include some kind of correction for partial oxidation. [-57.8]  per H 2 [-94.05]  per C = 2   57.8 H 2 C=CH 2 has extra energy to give off. One of its bonds (  ) is not very stabilizing, so it starts unusually high in energy. O1O1 O6O6 partially "pre-oxidized" Composition: Atom Additivity

How Complex Must a Model be to Predict Chemically Useful Energies? For physiology purposes you might be content with ± 5% in heat of combustion. But for predicting the equilibrium constant between c-hexane and c-hexanol, being off by 1% (9 kcal/mole) means being off in K eq by a factor of A useful model must go beyond composition. How about constitution? 10 7 !

C 6 H 12 Energy = CO 2 / H 2 O graphite / hydrogen  H combustion  H formation Energy (kcal/mole) Compared to What? easily measured How to measure? ( elements in their “standard states”)

HfHf APPENDIX I HEATS OF FORMATION From Streitwieser, Heathcock, & Kosower

HfHf APPENDIX I HEATS OF FORMATION From Streitwieser, Heathcock, & Kosower

HfHf APPENDIX I HEATS OF FORMATION From Streitwieser, Heathcock, & Kosower

formation cyclo minimum Expt. - Theory  H f + n  4.9 Group Additivity “unstrained” 2  -4.9 = -9.8 Strainless Theory (n  -4.9) ? From Streitwieser, Heathcock, & Kosower “Transannular” Strain similar c-hexane c-octane Small-Ring Strain

 ve Bond Energies Can one sum bond energies to get useful "Heats of Atomization"? Bond Additivity (between atoms and groups) From Streitwieser, Heathcock, & Kosower

How well can “Bond Energies” predict  H atomization ? Where does  H atomization come from?

C 6 H 12 Energy atoms  H atomization CO 2 / H 2 O graphite / hydrogen  H combustion  H formation Energy (kcal/mole) Compared to What? How Can You Know  H formation for an atom? = How to measure?

Atom Energy from Spectroscopy light energy X-Y X + Y H-H kcal/mole (  H f H = 52.1) O=O kcal/mole (  H f O = 59.6) CO kcal/mole X* + Y Maybe this is the observed transition at ? 141?  H f C=O =  H f H 0 2 _ _ _  H f O 0 2 _ _ _ X*’ + Y Or maybe this is the observed transition at ? 125? spectroscopic value precise, but uncertain Which to choose? CO Hf CHf C Hf OHf O graphite O 2 C + O graphite O (  H f C = 171.3) But Nobel Laureates Worried.

End of Lecture 35 Dec. 5, 2008 Copyright © J. M. McBride Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0) Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol. Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0