Archive for August, 2008

An update on Hydroxymethylene

A nice summary of the tunneling behavior of hydroxymethylene1 was just published by Bucher in Angewandte Chemie.2 Bucher strongly points out that the really novel part of this work is the very large barrier through which the proton tunnels. My blog post on this topic is here.


(1) Schreiner, P. R.; Reisenauer, H. P.; Pickard IV, F. C.; Simmonett, A. C.; Allen, W.
D.; Matyus, E.; Csaszar, A. G., "Capture of hydroxymethylene and its fast disappearance through tunnelling," Nature, 2008, 453, 906-909, DOI: 10.1038/nature07010.

(2) Bucher, G.; “Hydroxycarbene: Watching a Molecular Mole at Work,” Angew. Chem. Int. Ed., 2008, 47, 6957 – 6958, DOI: 10.1002/anie.200803195

carbenes &Schreiner &Tunneling Steven Bachrach 28 Aug 2008 No Comments

Cysteine conformers

Alonso and coworkers have developed the technique of laser ablation molecular beam Fourier transform microwave spectroscopy to detect biomolecules. In a recent paper1 they determined the structure of the glycine:one water complex – it is of the neutral configuration. They have now examined the conformations of cysteine2. The presence of the thiol side group adds considerable complexity to the problem due to the many conformations possible.

The experiment detected six conformers. Determining the structures responsible for each set of signals was made possible by comparing the experimental results with those determined by computation. Alonso computed 11 low energy conformations of cysteine at MP2/6-311++G(d,p). Then comparing the computed rotational constants and 14N nuclear quadrupole coupling tensor components with the experiment, they were able to match up all six experimental conformers with computed structures. The experimental and computed constants for the three most abundant structures are listed in Table 1. The geometries of all six conformers are drawn in Figure 1.

Table 1.Experimental and computed spectroscopic constants (MHz) for the three most abundant conformers of cysteine.2





























































aRelative energy in cm-1 computed at MP4/6-311++G(d,p)// MP2/6-311++G(d,p).

IIb (0.0)

Ia (450)

Ib (325)

IIa (527)

IIIβc (765)

IIIβb (585)

Table 1. Optimized structures of the six observed conformers of cysteine. Relative energies in cm-1 computed at MP4/6-311++G(d,p)//MP2/6-311++G(d,p). (Note – the geometries shown were optimized at PBE1PBE/6-311+G(d,p) since they MP2 structures are not available!)

This study demonstrates the nice complementary manner in which computation and experiment can work together in structure determination.


(1) Alonso, J. L.; Cocinero, E. J.; Lesarri, A.; Sanz, M. E.; López, J. C., "The Glycine-Water
Complex," Angew. Chem. Int. Ed. 2006, 45, 3471-3474, DOI: 10.1002/anie.200600342

(2) Sanz, M. E.; Blanco, S.; López, J. C.; Alonso, J. L., "Rotational Probes of Six Conformers of Neutral Cysteine," Angew. Chem. Int. Ed. 2008, DOI: 10.1002/anie.200801337


Cysteine: InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1

amino acids Steven Bachrach 26 Aug 2008 2 Comments

Hydroxymethylene tunnels through a large barrier

The very simple carbene hydroxymethylene, HOCH, has finally been prepared and characterized.1 Glyoxylic acid CHOCO2H is subjected to high-vacuum laser photolysis. It fragments into HOCH, which is then trapped into an argon matrix. The experimental IR frequencies match up very well with the CCSD(T)/cc-pVQZ harmonic frequencies of the trans isomer 1t that are also adjusted for anharmonic effects. The computed vertical excitation energy of 415 nm matches well with the experimental value of the maximum absorption in the UV/vis spectra of 427 nm.

The other very interesting experimental result is that HOCH has a lifetime of about 2 hours in the matrix, while the deuterated species DOCH is stable. To explain these results, Schreiner, Allen and co-workers optimized a number of structures on the PES at CCSD(T)/cc-pVQZ and computed their energies using the focal point technique. The optimized structures and their relative energies are given in Figure 1.

1t (0.0)

TS2 (29.7)

2 (-52.1)




1c (4.4)



Figure 1. Optimized CCSD(T)/cc-pVQZ structures of HOCH isomers and their Focal Point relative energies (kcal mol-1).1

The barriers for rearrangement from 1t are both very high. Rearrangement to formaldehyde 2 requires crossing a barrier of 29.7 kcal mol-1, while the barrier to convert to the cis isomer 1c is 26.8 kcal mol-1. (Note that from 1c a cleavage into CO and H2 can occur, but this barrier is another 47.0 kcal mol-1.) These barriers are too large to be crossed at the very low temperatures of the matrices. However, using the intrinsic reaction potential at CCSD(T)/cc-pVQZ and WKB theory, the tunneling lifetime of HOCH is computed to be 122 minutes, in excellent accord with the experiment. The lifetime for DOCH is computed to be over 1200 years. Thus, the degradation of hydroxymethylene is entirely due to tunneling through a very large classical barrier! This rapid tunneling casts serious doubt on the ability to ever identify any hydroxymethylene in interstellar space.


(1) Schreiner, P. R.; Reisenauer, H. P.; Pickard IV, F. C.; Simmonett, A. C.; Allen, W.
D.; Matyus, E.; Csaszar, A. G., "Capture of hydroxymethylene and its fast disappearance through tunnelling," Nature, 2008, 453, 906-909, DOI: 10.1038/nature07010.


1: InChI=1/CH2O/c1-2/h1-2H
2: InChI=1/CH2O/c1-2/h1H2

carbenes &focal point &Schreiner &Tunneling Steven Bachrach 19 Aug 2008 4 Comments

Review of my book

Here is another review of my book Computational Organic Chemistry; DOI: 10.1002/aoc.1406. This one is by John Brazier James Platts of Cardiff University and it appears in Applied Organometallic Chemistry. I do plead guilty to the charge of the interviews being USA-centric. This was due to scheduling problems that did not allow me to travel overseas.

Uncategorized Steven Bachrach 18 Aug 2008 No Comments

Modification to the Kick algorithm (mindless chemistry)

Addicoat and Mehta1 have made a modification of the “Kick” algorithm. Recall, that the Kick method (discussed in this previous blog post) takes a collection of atom coordinates and applies a random kick to each atom. This creates a new initial configuration and a geometry optimization is performed starting form this configuration. If hundreds of such configurations are chosen, one hopes to locate most if not all reasonable structures. The new variation is to create fragments in which the atoms are held fixed. Then the kick is applied to the fragment as a whole.

Among the examples demonstrated in the paper, only one is of an organic species. They examined the structure of the Gly-Trp peptide associated with two water molecules. They used two conformations of the Gly-Trp dipeptide. The kick was supplied to one of these conformers and to the two water molecules. They ended up locating 22 structures with the first conformer and 46 with the second, spanning a range of about 0.5 eV. It must be pointed out that many of these configurations are clearly noncompetitive by not maximizing the degree of hydrogen bonding that can be obtained. Furthermore, many other conformers of the dipeptide would need to be examined to really map out the full PES and definitively locate all reasonable low-energy configurations. (it is not necessary that the gas-phase low-energy conformers yield the lowest energy configurations of the water complex.) Nonetheless, this modified kick procedure offers a “quick-and-dirty” means of generating a wide variety of initial conditions for locating structures.


(1) Addicoat, M. A.; Metha, G. F., "Kick: Constraining a Stochastic Search Procedure with Molecular Fragments," J. Comput. Chem., 2008, DOI: 10.1002/jcc.21026

Uncategorized Steven Bachrach 14 Aug 2008 No Comments

Catalytic Claisen Rearrangments

There remains still new territory to explore even with such well-known reactions as the Claisen rearrangement. Jacobsen reports a catalyzed Claisen rearrangement where the catalyst is urea-based.1 Catalyst 1 produces modest to very reasonable % conversion in a series of simple Claisen rearrangements, as shown in Table 1.




Table 1. Claisen Rearrangements


% conv
(no catalyst)

% conv
(20% mol 1)







With the chiral catalyst 2, the Claisen rearrangement is both catalyzed and proceeds with large enantiomeric excess, as shown in the representative example Reaction 1.

Reaction 1

Jacobsen and Uyeda also reported the transition state for a model Claisen rearrangement catalyzed by a model guanidinium ion (Reaction 2) computed at B3LYP/6-31G(d). I have reproduced this calculation and the calculations for the both the catalyzed and uncatalyzed rearrangements, shown in Figure 1. In email communication with Dr. Jacobsen, I was able to confirm these energies against their own unpublished results.

Reaction 2

Uncatalyzed Reaction 2

Reactant: 0.0

TS: 25.73

Product 1: -11.04

Product 2: -13.69

Catalyzed Reaction 2

Reactant: 0.0

TS: 21.09

Product 1: -12.36

Product 2: -12.80

Figure 1. B3LYP/6-31G(d) optimized structures of the critical points of uncatalyzed and catalyzed Reaction 2. Relative energies in kcal mol-1.

The structures show the beneficial hydrogen bonds between the guanidinium anion and the carbonyl oxygens (or the ether oxygen of the reactant). In progressing from the transition state, both reactions first gives Product 1. This product conformer can than rotate to give the lower energy conformer Product 2. The activation energy of the catalyzed reaction is 4.64 kcal mol-1 lower than for the uncatalyzed reaction, demonstrating the benefit of the complexation in the transition state.

I want to thank Dr. Jacobsen and his graduate student Chris Uyeda for sharing their computational results with me for the preparation of this blog post.


(1) Uyeda, C.; Jacobsen, E. N., "Enantioselective Claisen Rearrangements with a Hydrogen-Bond Donor Catalyst," J. Am. Chem. Soc., 2008, 130, 9228-9229, DOI: 10.1021/ja803370x.

Claisen rearrangement &DFT Steven Bachrach 04 Aug 2008 No Comments

Another review of the book

A review of my book Computational Organic chemistry written by Christian Mück-Lichtenfeld, has appeared in Synthesis DOI: 10.1055/s-2008-1080541. A few things I particularly appreciate in the review is that Dr. Mück-Lichtenfeld recognized that the book in not intended to be a comprehensive review of computational organic chemistry but rather a survey of highlights, he mentions the book’s web site and blog, and favorably comments on the interviews that conclude each section.

Uncategorized Steven Bachrach 04 Aug 2008 No Comments