long overdue update

October 6, 2008

I was shocked to see how long it has been since I last posted something. It has been much easier to get caught up in other things and let this slip. I am hoping that with this post I can make a new start of it and put up something on a regular basis….at least once a week.

One item for today….Luc Montagnier has won the Nobel prize in medicine for discovering HIV. I imagine this will rankle a few feathers since Robert Gallo, who is also credited the discovery, was not included. For anyone who can remember this is not the first time that there was doubt about Gallo’s role in discovering thie virus. It will be interesting to see how this plays out in the next few weeks.

Personally I am against the idea of assigning credit for any scientific discovery to one or two individuals since it ignores the many other individuals who directly or indirectly contributed.


For Medicinal Purposes…

January 1, 2008

Role of beer as a possible protective factor in preventing Alzheimer’s disease

M.J. González-Muñoz et al. 

Food and Chemical Toxicology, Volume 46, Issue 1, January 2008, Pages 49-56


Useful Site…

December 17, 2007

Free computer tools in Structural Bioinformatics and Chemoinformatics

Separated at birth…

December 16, 2007

Phil Baran (from the pre-prof days) and Scott Baio (‘Chachi’ from ‘Happy Days’). The only way I can tell these two apart is that Phil is pictured with KC.  I bet if Phil were in high school around the same time I was (circa 1978-1982) he would have been tagged with the nickname ‘Chachi’ like my friend Larry who also bore a striking resemblance to this teen TV star.



December 13, 2007

Some Interesting Sites:

CrystalEye “The aim of the CrystalEye project is to aggregate crystallography from web resources, and to provide methods to easily browse, search, and to keep up to date with the latest published information.”

NIH Training Principles of Clinical Pharmacology “…a series of lectures that cover much of the scientific basis of the bridging discipline of clinical pharmacology.”

UC DAVIS M.I.N.D. Institute Distinguished Lecture Series Webcasts of the distinguished lecture series concerning primarily Autism research.

December 9, 2007

ts2.pngI have carried out simplified analysis of some recent papers on organocatalysis. The first example comes from a paper from the Jacobsen group (Raheem et al. J. Am. Chem. Soc. 2007, 13404, 10.1021/ja076179w) which describes a “H-bond donor” catalyst that effects an enantioselective Pictect-Spengler type reaction. Jacobsen attributes the selectivity to the substrate-halide-catalyst complex shown on the left. However, leaving the halide out of the complex yields an ion pair or perhaps a covalently bound intermediate as shown on the right. This brings the catalyst and substrate into closer contact than the halide-containing complex.


A ground-state model of the des-halide intermediate appears to work in explaining the enantioselectivity of the reaction as shown in the pictures below. In intermediate I, which leads to the minor enantiomer, the indole ring is not able to cyclize onto the acyliminium ion since it is being blocked by an appendage projecting from the catalyst. In contrast when the catalyst is bound to the other face of the acyliminium ion, as in intermediate II, the indole is free to cyclize which leads to the observed dominant enantiomer. Although Jacobsen indicates that some of their experimental work on the mechanism of catalysis makes the direct interaction of the catalyst with the acyliminium less likely, this intermediate is consistent, at least qualitatively, with the stereoselectivity reported for the paper. I am eager to see more details concerning the mechanism to see if this my interpretation holds up.

Intermediate I


Intermediate II


Intermolecular CH—pi interaction

September 14, 2007

 Dissecting out interactions between hydrophobic organic residues, particular those made in the context of a ligand binding to a protein (eg. enzyme or receptor) is difficult since it is hard to seperate the energy contributed by dissolution of the molecule from the energy of interaction with the protein.

 A recent Angewandte article (Angewandte Int. Ed., 2007, 6833) by Craig Wilcox from the University of Pittsburgh describes an interesting “molecular tool” for measuring weak “hydrophobic” interactions between organic residues which also takes into account the desolvation of the substituent.

The system is referred to as a “molecular torsion balance” and in some ways it resembles an old fashion two-pan balance. The actual molecule is a little more complicated looking, but it is rather straight forward to synthesize.


The balance measures the interaction of the test group (R) with the stationary phenyl group, while the corresponding rotomer places it “into solvent”. The group sheds these solvent molecules when the balance rotates to place it over the stationary phenyl group. The torsional equilibrium is directly proportional to the free energy difference (ΔG) between each rotamer. The equilibrium is easily measured using NMR.

In the study at hand the test substituents were all alkyl groups and therefore the type of interaction evaluated was that between the C-H portion of the alkyl groups and the p cloud of the phenyl ring. The results are shown in the table. There don’t appear to be any surprises in that the larger groups favor interaction with the aryl group and water enhances this effect due to desolvation.  Assuming that the CH-p interaction is the same in chloroform and water, the difference between ΔG (water) and ΔG (chloroform) provides a measure of the desolvation effect.


Seprated at birth

September 1, 2007

Eric….the present look says Anderson Cooper but will be there any relation to Mr. Burns in the future?

eric-jacobsen.jpg                               cooper1.jpg

Eric                                                 Anderson Cooper


Mr. Burns.

August 24th

August 24, 2007

I’ll confess that most of the theoretical methods are beyond me, but I found the premise of a recently published paper in Angewandte Int. Ed. intriguing.

Based on experiment and theory David Beratan (Duke University) shows that with certain chiral molecules the solvent directly contributes to the observed Optical Rotation (OR) of the solute.  They propose that the solvent sorrounding the chiral molecule creates a chiral shell, or in their words a “chiral imprint” and as such is capabable to exhibit an OR by itself  if the solvent molecules interact with the polarized light.

If true I think this finding has broader implications since it might be useful in the development of more accurate solvation models. For instance the results are not predicted by continuum solvent models.

Another interesting question is to what extent might the solvent shell contribute to the outcome of stereoselective reactions?


August 15, 2007

August 15, 2007

Why doesn’t Steven Nissen advocate for the banning of roller coasters?

A recent paper in JAMA (JAMA. 2007;298:739-741) studied the cardiovascular effects associated with riding a “modern” roller coaster. Among the CV-responses observed were:

  1. A pronounced increase in heart rate during and after the ride
  2. Asymptomatic sinus arrhythmias occurring in 44% of the riders
  3. 1 case of atrial fibrillation
  4. a case of asymptomatic nonsustained tachycardia