Posts Tagged ‘Stefan Grimme’

(another) WATOC 2017 report.

Tuesday, August 29th, 2017

Another selection (based on my interests, I have to repeat) from WATOC 2017 in Munich.

  1. Odile Eisenstein gave a talk about predicted 13C chemical shifts in transition metal (and often transient) complexes, with the focus on metallacyclobutanes. These calculations include full spin-orbit/relativistic corrections, essential when the carbon is attached to an even slightly relativistic element. She noted that the 13C shifts of the carbons attached to the metal fall into two camps, those with δ ~+80 ppm and those with values around -8 ppm. These clusters are associated with quite different reactivities, and also seem to cluster according to the planarity or non-planarity of the 4-membered ring. There followed some very nice orbital explanations which I cannot reproduce here because my note taking was incomplete, including discussion of the anisotropy of the solid state spectra. A fascinating story, which I add to here in a minor aspect. Here is a plot of the geometries of the 52 metallacyclobutanes found in the Cambridge structure database. The 4-ring can be twisted by up to 60° around either of the C-C bonds in the ring, and rather less about the M-C bonds. There is a clear cluster (red spot) for entirely flat rings, and perhaps another at around 20° for bent ones, but of interest is that it does form something of a continuum. What is needed is to correlate these geometries with the observed 13C chemical shifts to see if the two sets of clusters match. I include this here because in part such a search can be done in “real-time” whilst the speaker is presenting, and can then be offered as part of the discussion afterwards. It did not happen here because I was chairing the meeting, and hence concentrating entirely on proceedings!

  2. Stefan Grimme introduced his tight binding DFT method, an ultra fast procedure for computing large molecules and in passing noted the arrival of his D4 procedure (almost everyone currently uses D3 methods for this, including many of the results reported on this blog) for correcting for dispersion energies in molecules based on computed charge dependencies using the TBDFT methods. Thus we see dispersion as a property which is based on the wavefunction of the molecule, but still fast enough to accurately correct dispersion energies. He followed this with his automated procedures based on the TBDFT methods for computing full spin-spin coupled 1H NMR spectra of organic molecules. The core of this method is to recognise conformational and rotational freedoms and to compute the NMR properties for all identified isomers. These parameters are then Boltzmann averaged prior to computation of the final spin-coupled simulated frequency domain spectrum (rather than inverting this procedure by computing spin-coupled spectra of all rotamers and conformations and then averaging the spectral envelopes). This should widely revolutionise the interpretation of 1H NMR spectra by synthetic chemists.
  3. Another automated tool for synthetic chemists was presented by Jan Jenson, and can be seen here. It used MOPAC PM3 semi-empirical theory to compute relative proton affinities for a series of regioisomers as a prelude to predicting the position of aromatic electrophilic substitutions in heteroaromatic molecules. Try it out by putting a SMILES string into the box provided (e.g. COC1=CC=CC=C1) waiting a bit and seeing what the prediction is (it should be p- for the preceding example). During Q&A, a question was asked about the canonical “purity” of the SMILES (the one used in this tool comes from the Chemdraw program, which might not be identical to a SMILES for the same molecule produced by a different program), and whether an InChI descriptor might be better (also produced by Chemdraw, but perhaps a bit more canonical). Also asked was whether the prediction for an electrophile rather larger than a proton might not give good predictions? This one perhaps could be tested by readers, who could report back here?
  4. Walter Thiel completes the semi-empirical theme when he reported the new ODM2 method, the D now including dispersion. This is a powerful program, which includes e.g. full CI (configuration interaction + gradients) capability and is especially good for excited states, for dynamic simulations, and for combining these into dynamic photochemical simulations. This was applied to the chromophore in the famous “nanocar” in studying the dynamics of the photochemical rotation of the motor of the car (the thermally induced rotation was not studied). At the time that the nanocar caught my attention, I wondered about how the four independent molecular motors synchronised their rotations to allow the car to drive in a straight line. No doubt the answer is known, and if anyone reading this knows, please tell! It is probably a dynamics problem on four rotors (Walter reported just on one!).

Tags:, , , , , , , , , , , ,
Posted in Interesting chemistry, WATOC reports | 6 Comments »

WATOC2014 Conference report. Emergent themes.

Thursday, October 9th, 2014

This second report highlights two “themes”, or common ideas that seem to emerge spontaneously from diversely different talks. Most conferences do have them.

The first is “embedding“, which in this context means treating different parts of a probably complex molecular system at different levels of theory. Thus Emily Carter in her plenary described how a periodic crystal treated by density functional theory, or DFT could have an embedded component in which the electronic structures are described instead by multi-reference correlated wave functions (CAS-PT2). She illustrated this by discussing what happens when a triplet state oxygen molecule approaches the surface of an aluminium crystal, and (mostly) dissociates into surface bound oxygen atoms with Al-O bonds. The spin state of the oxygen changes smoothly to an overall singlet, with a rapid transfer of charge at the saddle point in the potential energy surface. The numbered of embedded Al atoms had to be at least a cluster of 14 to reproduce the observed reaction barriers (DFT on its own gets a zero barrier!). This sort of study is important in understanding the details of what is happening in metal surface catalysis.

Arieh Warshel then addressed the same theme with his own talk entitled Multiscale Modeling of Complex Biological Systems and Processes. Here you got quantum embedding in a mechanical force field description of some very large molecules. This was a broad brush talk, but what I did get out of it was the concept of asymmetry in molecular systems. Whereas an organic chemist thinks of asymmetry as often relating to just a single chiral carbon centre in a molecule, nature operates on vaster scales. Thus the enzyme ATPase has a molecular axle or spindle, which rotates to assemble the phosphate groups one at a time. This spindle rotates asymmetrically, i.e. always in a specific direction, and Warshel attempts to describe the origins of this rotational asymmetry at a molecular level. Well, this is Nobel prize winning stuff! He followed this up with filaments that “walk” along surfaces in one (asymmetric) direction, first lifting up one point of attachment, and then re-attaching at a different point such that the filament develops a clear sense of direction in its walk. This of course is all done with molecular dynamics, and (I think) has its origins in subtle electrostatics.

Stefan Grimme in his plenary also described dynamic processes, this time those that happen in a mass spectrometer when a molecule is ionised by electron impact. Removal of an electron produces a complex set of ionised states, in which many different single bonds may be weakened due to this ionisation. He developed simplified  DFT (sDFT) methods that can be applied to molecular dynamics, and assembled a “black box” which predicts the expected fragmentations over a time scale of a ps or so. By sampling the trajectories, he estimated the intensities of the various positively charged species and overlaid this on the observed EI-MS. The agreement was often spectacular. A particularly interesting example was the fragmentation of taxol. Here, no molecular ion is found, only much lighter ions. The molecular dynamics shows that rather than consecutive single-bond fragmentations, you instead get multiple bonds more or less all fragmenting at the same time. Tougher was to reproduce rearrangements, such as the McLafferty. Here, the semi-empirical method OM2 was more successful. His work means you can just “dial-a-mass-spectrum” and he speculates whether getting a good fit with the observed spectrum could tell you subtle aspects of the gas-phase molecular species, what its tautomeric state might be or perhaps even its conformation. He also described large-scale (800+) atom simulations of electronic circular dichroism (ECD) spectra of organometallic systems. Octahedral complexes can be prepared in chiral form, and this theoretical ECD treatment allows determination of absolute configuration of these often non-crystalline systems. Here you often need to compute 1000 or more electronic states, and if you have ever tried such ECD simulations, you will know that this is a lot of states!

We had been expecting Stefan to talk about dispersion effects in molecules, another emerging theme. Instead lots of other people mentioned them. In my talk I showed how including a D3-dispersion correction could dramatically change the predicted enantioselectivity of a chiral aldol condensation.[1]

The above observations of course cannot be in the least representative; typical of a modern conference there are five parallel sessions and 400+ posters, and so it represents a highly personal and selective snapshot.

References

    Tags:, , , , , , , , , , ,
    Posted in Interesting chemistry, WATOC reports | 1 Comment »