Archive for May, 2013

Is CCSD(T)/CBS really the gold standard?

The gold standard in quantum chemistry is the method that is considered to be the best, the one that gives accurate reproduction of experimental results. The CCSD(T) method is often referred to as the gold standard, especially when a complete basis set (CBS) extrapolation is utilized. But is this method truly accurate, or simply the highest level method that is within our reach today?

Řezáč and Hobza1 address the question of the accuracy of CCSD(T)/CBS by examining 24 small systems that exhibit weak interactions, including hydrogen bonding (e.g. in the water dimer and the waterammonia complex), dispersion (e.g. in the methane dimer and the methaneethane complex) and π-stacking (e.g. as in the stacked ethene and ethyne dimers). Since weak interactions result from quantum mechanical effects, these are a sensitive probe of computational rigor.

A CCSD(T)/CBS computation, a gold standard computation, still entails a number of approximations. These approximations include (a) an incomplete basis set dealt with by an arbitrary extrapolation procedure; (b) neglect of higher order correlations, such as complete inclusion of triples and omission of quadruples, quintuples, etc.; (c) usually the core electrons are frozen and not correlated with each other nor with the valence electrons; and (d) omission of relativistic effects. Do these omissions/approximations matter?

Comparisons with calculations that go beyond CCSD(T)/CBS to test these assumptions were made for the test set. Inclusion of the core electrons within the correlation computation increases the non-covalent bond, but the average omission is about 0.6% of the binding energy. The relativistic effect is even smaller, leaving it off for these systems involving only first and second row elements gives an average error of 0.1%. Comparison of the binding energy at CCSD(T)/CBS with those computed at CCSDT(Q)/6-311G** shows an average error of 0.9% for not including higher order configuration corrections. The largest error is for the formaldehyde dimer (the complex with the largest biding energy of 4.56 kcal mol-1) is only 0.08 kcal mol-1. If all three of these corrections are combined, the average error is 1.5%. It is safe to say that the current gold standard appears to be quite acceptable for predicting binding energy in small non-covalent complexes. This certainly gives much support to our notion of CCSD(T)/CBS as the universal gold standard.

An unfortunate note: the authors state that the data associated with these 24 compounds (the so-called A24 dataset) is available on their web site (, but I could not find it there. Any help?


(1) Řezáč, J.; Hobza, P. "Describing Noncovalent Interactions beyond the Common Approximations: How Accurate Is the “Gold Standard,” CCSD(T) at the Complete Basis Set Limit?," J. Chem. Theor. Comput., 2013, 9, 2151–2155, DOI: 10.1021/ct400057w.

QM Method Steven Bachrach 28 May 2013 3 Comments

ORD of methyloxirane

Computing the optical rotation of simple organic molecules can be a real challenge. One of the classic problems is methyloxirane. DFT typically gets the wrong sign, let alone the wrong value. Cappelli and Barone1 have developed a QM/MM procedure where methyloxirane is treated with DFT (B3LYP/aug-cc-pVDZ or CAM-B3LYP/aubg-cc-pVDZ). Then 2000 arrangements of water about methyloxirane were obtained from an MD simulation. For each of these configurations, a supermolecule containing methyloxirane and all water molecules with 16 Å was identified. The waters of the supermolecule were treated as a polarized force field. This supermolecule is embedded into bulk water employing a conductor-polarizable continuum model (C-PCM). Lastly, inclusion of vibrational effects, and averaging over the 2000 configurations, gives a predicted optical rotation at 589 nm that is of the correct sign (which is not accomplished with a gas phase or simple PCM computation) and is within 10% of the correct value. The full experimental ORD spectrum is also quite nicely matched using this theoretical approach.


(1) Lipparini, F.; Egidi, F.; Cappelli, C.; Barone, V. "The Optical Rotation of Methyloxirane in Aqueous Solution: A Never Ending Story?," J. Chem. Theor. Comput. 2013, 9, 1880-1884, DOI: 10.1021/ct400061z.



DFT &Optical Rotation Steven Bachrach 15 May 2013 2 Comments

o-phenylene polymers – the unwritten post

I was intending to write a post regarding an interesting paper on o-phenylene polymers. This paper describes experiments and computations on the hexamer, with particular attention paid to arene-arene interactions.1 These compounds fold into a helix, which has obvious application to many biological systems (DNA and the α-helix of peptides).

One of the things I am attempting to convey in this blog is the advantage of electronic communication in the sciences. In particular, I incorporate 3-dimensional structures of molecules in a way that allows the reader to interact with the molecule through a Java applet. (If you haven’t done this yet, any of the 3-D static images in this blog are actually linked to active structures – simply click on them and allow the Java applet to load.)

Now the paper by Hartley and co-workers does include supporting information with the coordinates of the different conformers of the o-phenylene hexamer, and I was all set to create images and incorporate the active molecules within a post. However, the pdf version of the supporting materials, while looking fine when viewed, actually has destroyed the data. I cannot copy-and-paste the coordinates into any program – the coordinates are completely corrupted! This is yet another example of how pdf is perhaps one of the worst choices for data deposition, as Peter Murray-Rust has often noted in his blog.

So until the supporting materials are fixed in some way, I will not, really can not, write up a post on it. Authors please remember to submit useful supporting materials!


(1) Mathew, S. M.; Engle, J. T.; Ziegler, C. J.; Hartley, C. S. "The Role of Arene–Arene Interactions in the Folding of ortho-Phenylenes," J. Am. Chem. Soc. 2013, 135, 6714-6722, DOI: 10.1021/ja4026006.

Aromaticity Steven Bachrach 08 May 2013 2 Comments