Monthly Archives: October 2014

Atoms in Molecules (QTAIM) – Flash lesson


As far as population analysis methods goes, the Quantum Theory of Atoms in Molecules (QTAIM) a.k.a Atoms in Molecules (AIM) has become a popular option for defining atomic properties in molecular systems, however, its calculation is a bit tricky and maybe not as straightforward as Mulliken’s or NBO.

Personally I find AIM a philosophical question since, after the introduction of the molecule concept by Stanislao Cannizzaro in 1860 (although previously developed by Amadeo Avogadro who was dead at the time of the Karlsruhe congress), the questions of whether or not an atom retains its identity when bound to others? where does an atom end and the next begins? What are the connections between atoms in a molecule? are truly interesting and far deeper than we usually consider because it takes a big mental leap to think about how matter is organized to give rise to substances. Particularly I’m very interested with the concept of a Molecular Graph which in turn is concerned with the way we “draw lines” to form conceptual molecules. Perhaps in a different post we can go into the detail of the method, which is based in the Laplacian operator of the electron density, but today, I just want to collect the basic steps in getting the most basic AIM answers for any given molecule. Recently, my good friend Pezhman Zarabadi-Poor and I have used rather extensively the following procedure. We hope to have a couple of manuscripts published later on. Therefore, I’ve asked Pezhman to write a sort of guest post on how to run AIMALL, which is our selected program for the integration algorithm.

The first thing we need is a WFN or WFX file, which contains the wavefunction in a Fortran unformatted file on which the Laplacian integration is to be performed. This is achieved in Gaussian09 by incluiding the keyword output=wfn or output=wfx in the route section and adding a name for this file at the bottom line of the input file, e.g.

filename.wfn

(NOTE: WFX is an eXtended version of  WFN; particularly necessary when using pseudopotentials or ECP’s)

Analyzing this file requires the use of a third party software such as AIMALL suite of programs, of which the standard version is free of charge upon registration to their website.

OpenAIMStudio (the accompanying graphical interface) and select the AIMQB program from the run menu as shown in figure 1.

 

Figure 1

Figure 1

Select your WFN/WFX file on which the calculation is to be run. (Figure 2)

 

Figure 2

Figure 2

You can control several options for the integration of the Laplacian of the electron density as well as other features. If your molecules are simple enough, you may go through with a successful and meaningful calculation using the default settings. After the calculation is finished, several result files are obtained. We’ll work in this tutorial only with *.mpgviz (which contains information about the molecular graph, MG) and *.sum (which contains all of  needed numerical data).

Visualization of the MG yields different kinds of critical points, such as: 1) Nuclear Attractor Critical Points (NACP); 2) Bond Critical Points (BCP); 3) Ring CP’s (RCP); and 4) Cage CP’s (CCP).

Of the above, BCP are the ones that indicate the presence of a chemical bond between two atoms, although this conclusion is not without controversy as pointed out by Foroutan-Njead in his paper: C. Foroutan-Nejad, S. Shahbazian and R. Marek, Chemistry – A European Journal, 2014, 20, 10140-10152. However, at a first approximation, BCP’s can help us to explore chemical interactions.

Now, let’s go back to visualizing those MGs (in our examples we’ve used methane and ethylene and acetylene). We open the corresponding *.mpgviz file in AIMStudio and export the image from the file menu and using the save as picture option (figure 3).

Figure 3

Figure 3

The labeled atoms are NACP’s while the green dots correspond to BCP’s. Multiplicity of a bond cannot be discerned within the MG; in order to find out whether a bond is a single, double or triple bond we have to look into the *.sum file, in which we’ll take a look at the bond orders between pairs of atoms in the section labeled “Diatomic Electron Pair Contributions and Delocalization Data” (Figure 4).

Figure 4

Figure 4

Delocalization indexes, DI’s, show the approximate number of electrons shared between two atoms. From the above examples we get the following DI(C,C) values: 1.93 for C2H4 and 2.87 for C2H2; on the other hand, DI(C,H) values are  0.98 for CH4, 0.97 in C2H4 and 0.96 in C2H2. These are our usual bond orders.

This is the first part of a crash tutorial on AIM, in my opinion this is the very basics anyone needs to get started with this interesting and widespread method. Thanks to all who asked about QTAIM, now you have your long answer.

Thanks a lot to my good friend Dr Pezhman Zarabadi-Poor for providing this contribution to the blog, we hope you all find it helpful. Please share and comment.

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WATOC 2014 – Virtual edition


I had a blast last week at WATOC2014 in Santiago de Chile! It was a wonderful opportunity to find old friends, meet new ones and listen to some exciting research done around the world, as well as some of the classics such as Pekka Pyykkö, who was awarded the Schrödinger medal. I decided to share my talk on SlideShare.com but also here because I found at WATOC that many many people seem to like this little space of mine! I was shocked, flattered but mostly happy to know that this little blog of mine is well regarded.

So, without further ado, here is my presentation at WATOC2014, please read the captions on each image for context. Feel free to make any comments, sharing or liking. Thanks for clicking!

Self explanatory :)

Self explanatory 🙂

Administration of a drug follows one of these two extreme pharmacokinetic pathways. Either way, drugs accumulate in non-target tissues, are wasted and cause undesired secondary effects.

Administration of a drug follows one of these two extreme pharmacokinetic pathways. Either way, drugs accumulate in non-target tissues, are wasted and cause undesired secondary effects.

Ideally, a drug should arrive to the target tissue. Several polymolecular drug carriers have been developed.

Ideally, a drug should arrive to the target tissue. Several polymolecular drug carriers have been developed.

In terms of monomolecular carriers, cyclodextrines have shown moderate success.

In terms of monomolecular carriers, cyclodextrines have shown moderate success.

Calixarenes offer a more chemically-tunable alternative.

Calixarenes offer a more chemically-tunable alternative.

We decided to go with drugs for the treatment of chronic myeloid leukemia

We decided to go with drugs for the treatment of chronic myeloid leukemia

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Interaction energies were calculated with the NBODel approach, in which elements of the Fock Matrix common to two molecular fragments are deleted

Interaction energies were calculated with the NBODel approach, in which elements of the Fock Matrix common to two molecular fragments are deleted

This deletion yields a new Fock matrix which is re-diagonalized; the increase in energy is ascribed to the interaction between both fragments.

This deletion yields a new Fock matrix which is re-diagonalized; the increase in energy is ascribed to the interaction between both fragments.

GTP was a small place to start (chemical space blocked due to animation lost in translation)

GTP was a small place to start (chemical space blocked due to animation lost in translation)

Interaction energies obtained

Interaction energies obtained

Hydrogen bonds and pi - pi interactions account for the large interaction energies

Hydrogen bonds and pi – pi interactions account for the large interaction energies

Diapositiva13

Detail of the interactions in some of the obtained geometries

 

 

MD simulations show the progress of the "release" process.

MD simulations show the progress of the “release” process.

So we moved to a larger drug with more degrees of freedom (and a comercial one too)

So we moved to a larger drug with more degrees of freedom (and a comercial one too)

Chemical space increased regard to the one used with GTP.

Chemical space increased regard to the one used with GTP.

In both cases, two insertion modes were considered.

In both cases, two insertion modes were considered.

Some results...

Some results…

100ns of MD show three kinds of structures (inserted, partially released and totally released)

100ns of MD show three kinds of structures (inserted, partially released and totally released)

PMF US - the profile of release tells us if the carrier is way too strong to be a carrier at all.

PMF US – the profile of release tells us if the carrier is way too strong to be a carrier at all.

Where do we go from here?

Where do we go from here?

Second generation CML drugs; however Bosutinib poses a funny challenge

Second generation CML drugs; however Bosutinib poses a funny challenge

A comercial error has released two isomers to the market, only one of them actually works. CAN WE GENERATE A RECOGNITION AGENT??

A comercial error has released two isomers to the market, only one of them actually works. CAN WE GENERATE A RECOGNITION AGENT??

I know, some results need  some attention, I know, trust me.

I know, some results need some attention, I know, trust me.

Also, Imatinib is cardiotoxic. We research now the competence between allegedly affected enzymes and the carriers to at least delay the toxic effect.

Also, Imatinib is cardiotoxic. We research now the competence between allegedly affected enzymes and the carriers to at least delay the toxic effect.

Diapositiva26

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Diapositiva27

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Thanks to all of these wonderful guys who made all publications possible (and also those who gave the money)

Thanks to all of these wonderful guys who made all publications possible (and also those who gave the money)

(The view from my office in Toluca) Any questions?

(The view from my office in Toluca, Mexico) ANY QUESTIONS? Write it in the comments section!

 

If you made it this far, let me tell you that this is also available at Slideshare.com 🙂

Thanks for reading, commenting and sharing!

WATOC 2014


I inexcusably forgot to write about my visit to WATOC2014 but as they say it’s better late than never. I’ve been here in Santiago de Chile for a day and a half now attending mostly to session 5 “applications to compelling problems”. WATOC (World Association of Theoretical and Computational Chemists) is probably the largest conference in our speciality and some of the big names are here which makes me very nervous to present my talk!

My talk will be very similar to the one presented in the last ACS meeting in San Francisco, in silico design of monomolecular drug delivery agents based on calix[n]arene macrocycles.

I wont try to report from WATOC, I’m not any good at that but will for sure be available if anyone wants to contact me.

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