Category Archives: Computational Chemistry

XIV Mexican Reunion on Theoretical Physical Chemistry

Each year the Mexican community who works in the realm of computational and theoretical chemistry gathers to share the most recent work done around our country. This year, I tried to live Tweet the event and although I failed miserably in doing so -as well as in convincing others to join me- I’m trying to put together the things that caught my attention. I also tried to Storify it but I cannot embed the result here in WordPress.

María Eugenia “Maru” Sandoval just came back from a short stay in Spain where she worked with Prof. David Casanova on Singlet Fission theory applied to her work on photosynthesis. Here work was presented as a poster although we would have preferred she gave a talk.


Also, Guillermo “Memo” Caballero presented his recent developments in reaction mechanisms.   

Below there is a list of Tweets from the conference. If you are interested in any of these items please contact me for further information, or just, you know, google the people mentioned in each Tweet, it shouldn’t be too hard.



Of course when you have a large meeting with so many people working with and on Density Functional Theory (DFT) you know that Perdew’s suggested ‘Jacob’s ladder’ of functional quality for chemical accuracy is bound to show up a few times.
I actually wrote a post that gravitates around this issue but using figurative painting as an analogue. You may find it here






That is Pt “double bond” Sn. By no means I’m equating platinum to tin. No sir. Mulliken’s population analysis should not even been brought up anymore, should it?



If there is water and ice on Mars then most definitely should be clathrates. (Please excuse the misspelling throughout, though.)


The rest are the previous announcements which were aimed to generate the momentum for the live tweeting thing.



I hope I can make this a thing next year during the 15th edition of RMFQT. I had the honor to be the first speaker and I will upload my presentation soon.

A personal artistic impression of the CompChem Landscape 

In a nutshell, computational chemistry models are about depicting, reproducing and predicting the electronic-based molecular reality. I had this conversation with my students last week and at some point I drew a parallel between them and art in terms of how such reality is approached.

Semi empirical methods
Prehistoric wall paintings depict a coarse aspect of reality without any detail but nevertheless we can draw some conclusions from the images. In the most sophisticated of these images, the cave paintings in Altamira, we can discern a bison, or could it be a bull? but definitely not a giraffe nor a whale, most in the same way Hückel´s method provides an ad hoc picture of π electron density without any regard of the σ portion of the electron density or the conformational possibilities (s-cis and s-trans 1,3-butadiene have the same Hückel description).

More sophisticated semi-empirical Hamiltonians like PM3 or PM6 have better parametrizations and hence yield better results. We are still replacing a lot of information for experimental or adjusted parameters but we still cannot truly adopt it as truthful. Take this pre-medieval painting of one of the first Kings of England, Aelred the Unready. It is, by today standards, a good children´s drawing and not a royal portrait, we now see more detail and can discern many more features yielding a better description of a human figure than those found in Altamira or Egypt.


Æthelred the Unready King of England ca. 1000 BC


HF is the simplest of ab initio methods, meaning that no experimental results or adjustable parameters are introduced. Even more so, from the HF equations for a multi-electron system that complies with Pauli’s exclusion principle the exchange operator arises as a new quantum feature of matter with no classical analogue. Still, there are some shortcomings. Correlation energy is disregarded and most results vary according to the basis set employed. Take the impressionist movement, specially in France: In Monet´s Lady with Umbrella we have a more complicated composition, we observe many more features and although we have a better description of color composition some details, like her face, remain obscure. The impressionists are characterized by their broad strokes, the thicker the strokes the harder it is to observe details similar to what happens in HF when we change from a small to a large basis set, respectively.


Woman with a parasol – Her face or the identity of the flowers at her feet are indistinguishable yet we might be safe to say its springtime.

CI (Configurations Interaction)
Extension of HF to a multi-reference method yields better results. In CI we take the original guess wavefunction -as expressed through a Slater Determinant- and extend it with one or many more wavefunctions; thus a linear combination of Slater Determinants gives rise to a broader description of the ground state because other electronic configurations are involved to include more details like the ionic and covalent pictures (configurations). The more terms we include the more real the results feel. If we take classical figurative paintings we have a similar result; most of these paintings are constituted of many elements and the more realistically each element is captured the more real the whole composition looks even if some are just merely indicated.


Flaming June by Lord Leighton – Extreme details on the fabrics and the sea in the background makes us oblivious to the less detailed foot


In Edwards Much’s the scream, we might think we have lost some information again and went back to impressionism but we know this is actually an expressionist painting; we can now not only observe details of the figurative portion of the image but Munch has captured his subject´s fear in the form of distorsions on the subjective reality. In this way, CCSD(T), full-CI and CASPT2 methods provide a description of the ground as well as the excited states which -in experimental reality- are only accessed through a perturbation of the elecron density by electromagnetic radiation. Something resembling radiation has perturbated the subject in The Scream rendering him frightened and wondering how to return to his ground state or if such thing will be even possible.


The Scream by Edward Munch – what sort of perturbation got this guy’s fears out?


Density Functional Methods

At least due to its widespread use, DFT has risen as the preferred method. One of the reasons behind its success is the reduced computing time when compared to previous ab initio methods. So DFT is pretty much like photography, in which reality is captured in full but only apparently after selecting a given lens, an exposition, a filter, shutter speed and the occasional Photoshop for correcting issues such as aliasing. In photography, as in DFT, all details concerning the procedure or method for capturing an uncanny reproduction of reality must be stated in every case for reproduction purposes.

Now, in the end it all comes down to Magritte’s Pipe. Ceci n’est pas une pipe -or, ‘this is not a pipe’- reminds us that painting as with modeling we don’t get reality but rather a depiction of it. In this famous painting we look at an image that in our heads resembles that of a pipe but we cannot grab it, fill it with tobacco and smoke it.


This isn’t even Magritte’s painting! Let alone a pipe

The image above is a digital file, which translated becomes a scaled reproduction of an image painted by Magritte in which we see the 2D projection of the image of an object that reminds us of a pipe. In fact, the real name of this work is The Treachery of Images, definitely quite an epistemology problem on perception and knowledge but before I get too metaphysical I should finish this post.

Can you find where cubism or surrealism should be placed? with MPn methods, perhaps?

Partial Optimizations with Gaussian09

Sometimes you just need to optimize some fragment or moiety of your molecule for a number of reasons -whether because of its size, your current interest, or to skew the progress of a previous optimization- or maybe you want just some kind of atoms to have their positions optimized. I usually optimize hydrogen atoms when working with crystallographic files but that for some reason I want to preserve the rest of the molecule as refined, in order to keep it under a crystalline field of sorts.
Asking Gaussian to optimize some of the atoms in your molecule requires you to make a list albeit the logic behind it is not quite straightforward to me. This list is invoked by the ReadOptimize keyword in the route section and it includes all atoms by default, you can then further tell G09 which atoms are to be included or excluded from the optimization.
So, for example you want to optimize all atoms EXCEPT hydrogens, then your input should bear the ReadOptimize keyword in the route section and then, at the end of the molecule specification, the following line:

atoms notatoms=H

If you wish to selectively add some atoms to the list while excluding others, here’s an example:

atoms=C H S notatoms=5-8

This list adds, and therefore optimizes, all carbon, hydrogen and sulfur atoms, except atoms 5, 6, 7 and 8, should they be any of the previous elements in the C H S list.
The way I selectively optimize hydrogen atoms is by erasing all atoms from the list -using the noatoms instruction- and then selecting which are to be included in the list -with atoms=H-, but I haven’t tried it with only selecting hydrogen atoms from the start, as in atoms=H

noatoms atoms=H

I probably get very confused because I learned to do this with the now obsolete ReadFreeze keyword; now it sometimes may seem to me like I’m using double negatives or something – please do not optimize all atoms except if they are hydrogen atoms. You can include numbers, ranks or symbols in this list as a final line of your input file.

Common errors (by common I mean I’ve got them):

Lets look at the end of an input I just was working with:

>  AtmSel:  Line=”P  0″
>  Maximum list size exceeded in AddBin.
>  Error termination via Lnk1e in…

AtmSel is the routine which reads the atoms list and I was using a pseudopotential on phosphorous atoms, I placed the atoms list at the end of the file but it should be placed right after the coordinates and the connectivity matrix, should there be one, and thus before any external basis set or pseudopotential or any other specification to be read by Gaussian.

As a sort of test you can use the instruction:

%kjob l103

at the Link0 section (where your checkpoint is defined). This will kill the job after the link 103 is finished, thus you will only get a list of what parameters were frozen and which were active. Then, if things look ok, you can run the job without the %kjob l103 instruction and get it done.

As usual I hope this helps. Thanks for reading except to those who didn’t read it except for the parts they did read.

Comparing the Relative Stability of Non-Equivalent Molecules

How do you compare the stability of two or more compounds which differ in some central atom(s)?

If you simply calculate the energy of both compounds you get a misleading answer since the number of electrons is different from one to the next -in fact, the answer is not so much misleading as it is erroneous. Take compounds 1 and 2 shown in figure 1, for example. Compound 1 was recently synthesized characterized through X-Ray crystallography by my friend Dr. Monica Moya’s group; compound 2 doesn’t exist and we want to know why – or at least know if it is relatively unstable respect to 1.

Figure 1. Compound 1 exists but compound 2 is apparently less stable. Is it?

Figure 1. Compound 1 exists but compound 2 is apparently less stable. Is it?

Although stoichiometry is the same, varying only by the substitution of Ga by Al the number of electrons is quite different. We then made the following assumption: Since the atomic radii of Ga and Al are quite similar (according to the CCDC their respective covalent radii are 122[4] and 121[3] pm), relative stability must rely on the bonding properties rendering 2 harder to obtain, at least through the method used for 1. The total energy for compound 1 was calculated at the M06-2X/6-31G(d,p) level of theory; then both Al atoms were changed by Ga and the total energy was calculated again at the same level. Separately, the energy of isolated Ga and Al atoms were calculated. Compensating the number of electrons was now a simple algebraic problem:

ΔE = E(MnBxOy) – nEM + nEM’ – E(M’nBxOy)

 The absolute energy difference E1 – E2 is staggering due to the excess of 36 electrons in 2. But after this compensation procedure we now have a more reliable result of ΔE value of ca. 81 kcal/mol in favor of compound 1. In strict sense, we performed geometry optimizations at various stages: first on compound 1 to remove the distorsions due to the crystal field and then on the substituted compound 2 to make sure Ga atoms would find a right fit in the molecule but since their covalent radii are similar, no significant changes in the overall geometry were observed confirming the previous assumption.

We now have the value of the energy difference between 1 and 2 and other similar cases, the next step is to find the distal causes of the relative stability which may rely on the bonding properties of the Ga-O bond respect to the Al-O bonds.

What do you think? Is there another method you can share for tackling this problem? Please share your thoughts on the comments section.

Thanks for reading.

Restarting Calculations from rwf Files – Gaussian

Having a long calculation terminated just because it ran out of time in the queue is very frustrating; even more so if restarting it from the last accesible point is hard to do.

I have recently performed some particularly demanding calculation: Basis Set Superposition Error (BSSE) with the Counterpoise method and second order Moller-Plesset perturbation theory calculation (MP2). The calculation ran out of time but I was able to restart it because I had the rwf file! My input looked a bit like this:

#p mp2/GEN counterpoise=2 maxdisk=200GB

So here is how it works.

The very first line of your calculation gives you the process ID number which is not necessarily the same as the PID given by the queue system (in fact, is not the same because the latter corresponds to the submitted script, not the instructions in it i.e. your calculation)

 Entering Gaussian System, Link 0=g09
 Initial command:
 /opt/SC/aplicaciones/g09-C.01/l1.exe /tmpu/joaqbf_g/joaqbf/Gau-38954.inp 
 Entering Link 1 = /opt/SC/aplicaciones/g09-C.01/l1.exe PID=     38955.

(emphasis in red is mine)

This is the number you want to write down. You will need to find the corresponding rwf file (usually in your SCRATCH directory) as Gau-PID.rwf (in the aforementioned case, Gau-38955.rwf). If you are a bit paranoid like myself you want to copy and keep this file safe but be aware that these are very long files, in my case it was 175 GB long. Now you need to launch your calculation again with the following input:


Title Card

# restart

rest of input

You can add all other controls to the Link0 section such as %nprocshared or %mem according to your needs.

I’m pretty sure it should work for other kinds of calculations in which taking from the checkpoint file is not as easy, so if you run into this kind of problems, its worth the try.

Fluorescent Chemosensors for Chloride in Water – Sensors and Actuators B: Chemical

A new publication is now available in which we calculated the binding properties of a fluorescent water-soluble chemosensor for halides which is specially sensitive for chloride. Once again, we were working in collaboration with an experimental group who is currently involved in developing all kinds of sustainable chemosensors.

The electronic structure of the chromophore was calculated at the M06-2X/6-311++G(d,p) level of theory under the SMD solvation model (water) at various pH levels which was achieved simply by changing the protonation and charges upon the ligand. Wiberg bond indexes from the Natural Population Analysis showed strong interactions between the chloride ion and the chromophore. Also, Fukui indexes were calculated in order to find the most probable binding sites. A very interesting feature of this compound is its ability to form a cavity without being a macrocycle! I deem it a cavity because of the intramolecular interactions which prevent the entrance of solvent molecules but that can be reversibly disrupted for the inclusion of an anion. In the figure below you can observe the remarkable quenching effect chloride has on the anion.


A quick look to the Frontier Molecular Orbitals (FMO’s) show that the chloride anion acts as an electron donor to the sensor.

Frontier Molecular Orbitals

Frontier Molecular Orbitals

If you are interested in more details please check: Bazany-Rodríguez, I. J., Martínez-Otero, D., Barroso-Flores, J., Yatsimirsky, A. K., & Dorazco-González, A. (2015). Sensitive water-soluble fluorescent chemosensor for chloride based on a bisquinolinium pyridine-dicarboxamide compound. Sensors and Actuators B: Chemical, 221, 1348–1355.

Thanks to Dr. Alejandro Dorazco from CCIQS for asking me to join him in this project which currently includes some other join ventures in the realm of molecular recognition.

A new chemist is graduated

It is with great pleasure that I announce the graduation of another member of our research group: Luis Enrique “Kike” Aguilar defended his BSc thesis yesterday and is now counting the days left for the Autumn when he’ll move to the Netherlands for a masters in computational chemistry.

Luis Enrique, Kike, calculated the interaction energies of 144 different inclusion complexes where calix and thia-calix[n]arenes were once again the chosen hosts (36 of them) and two drugs for the treatment of chronic myeloid leukemia (CML), namely Sorafenib and Bosutinib, were the guests.

The publication of the corresponding article in which we once again were fortunate enough to count with the collaboration of Dr. Rodrigo Galindo from Utah University in the molecular dynamics section, is still pending but we’re confident enough that it wont take much longer until it’s out there.

Kike is a very diligent student with great learning skills, I’m sure he’ll succeed in any enterprise he sets himself off.  Congratulations, Kike! Thanks for being a part of our research but more importantly for being a part of our community.


Two more students graduated!

It is with great pleasure that I’d like to announce the thesis defense of Guillermo “Memo” Caballero and Howard Diaz who in past days became the second and third students, respectively, to get their B.Sc. degrees with theses completed at our lab. I want to publicly thank them for their hard work which hasn’t only contributed with a thesis to our library but will soon contribute with research papers to our count.

Guillermo “Memo” Caballero worked on the calculation of a reaction mechanism that cannot happen. He started as a synthetic chemist and when he hit a wall at the lab he thought computational chemistry might help him get synthesis on the right direction. He has proven now that the aromatization process of a substituted glutarimide into the corresponding pyridine can only proceed only if substituents with a very strong electron withdrawing effect are used. For two reaction mechanisms proposed, both of them intramolecular rearrangements and only one of them concerted, the calculated energy barriers to reach for the corresponding transition states (QST2 and QST3 methods used) are higher than a pyrolitic decomposition. Memo found also that the delocalization of the pi electron system and its extent goes a long way into the stabilization of the non-aromatic analogue. At first we wanted to treat this problem as a tautomeric equilibrium but since we cannot observe the aromatic tautomer there is no equilibrium and hence no tautomerism. We are still thinking how to name this correspondence between the two compounds when we submit the corresponding paper. It must be said that Guillermo graduated with the highest honors in a most deserved way.

Howard Diaz worked on the design of molecular blockers for the entrance process of the HIV-1 virus into lymphocytes through the GP120 protein. Six known blockers based on phenyl-indoyl-urea were assessed through docking, the binding site of the GP120 protein was described in terms of the interactions formed with each on these compounds and that served as the basis for what in the end came up to be a 36 compound library of blockers, whose structures were first optimized at the B3LYP/6-31G** level of theory. All the 42 blockers were docked in the binding site of the protein and a thorough conformational search was performed. From this set, lead compounds were selected in terms of their binding energies (first calculated heuristically) and further studied at the Density Functional Theory, B97D/cc-pVTZ in order to study the electronic structure of the blocker when interacting with a selection of residues at the binding site. Interaction energies calculated at the quantum level are consistent with the complex formation but since we had to cut the protein to only a few residues little correlation is found with the first calculation; this is fine and still publishable, I just wish we had a more seamless transition between heuristics and quantum chemical calculations. Wiberg indexes were very low, as consistent with a hydrophobic cavity, and delocalization energies calculated with second order perturbation theory analysis on the Natural Bond Orbitals revealed that the two most important interactions are C-H…π and Cl…π, these two were selected as key parameters in our design of new drugs for preventing the HIV-1 virus to bind lymphocytes-T; now we only need to have them synthesized and tested (anyone interested?).

Thank you guys for all your hard work, it has truly payed off. I’m completely certain that no matter what you do and where you go you will be very successful in your careers and I wish you nothing but the very best. This lab’s doors will always remain open for you.


Physical Chemistry Meeting and CCIQS Symposium

Materials Research Institute at Morelia Michoacan (southern Mexico)

Materials Research Institute at Morelia Michoacan (southern Mexico)

So many events going on and so little time to blog about.
Two weeks ago, four members of this group traveled to Morelia in southern Mexico to present their research at the XIII Mexican Physical Chemistry Meeting. The next week after that, they all brought their posters back to Toluca for the internal symposium at CCIQS, where a masters student, María Eugenia, gave a small talk about her research project concerning photosynthesis in bacteria. Below, a short description of their projects is presented in order of seniority.

María Eugenia “Maru” Sandoval
Maru is working in photosynthesis of green sulfur bacteria. Her research deals with the excited states calculations at the Time Dependent DFT level for describing the first stages of photon interaction in antennae complexes of the photosystem II, namely the Fenna-Matthews-Olsen (FMO) complex, which was selected due to its relative structural simplicity over that of more evolved organisms. Maru also gave a talk at the internal Symposium back in Toluca the very next week where she got a positive feedback which will be used in her project.

Howard Diaz
One of the many strategies out there for treatment of HIV-1 infections is to block those proteins used to anchor the virus to a healthy cell. Sort of getting the virus’ hands busy so they can’t attach to a host. 60+ new compounds derived from thiourea were screened and assessed in their interactions with protein GP120, the protein to which the attachment is made, through docking and DFT calculations. Lead compounds are reported. It must be stressed that Howard got an award at CCIQS for having one of the best posters out of 70 in the entire symposium. Kudos and thanks to you, Howard! We now have some MD simulations in order.

Howard Diaz -  GP120 blockers for HIV-1

Howard Diaz – GP120 blockers for HIV-1

Guillermo “Memo” Caballero
His project has some nice philosophical implications if you ask me. Memo started as an experimental chemist and when he ran into a wall trying to obtain a pyridine from the non-aromatic analogue (glutarimide), he came to our group to run some calculations and find out how to force the aromatization process, or at least rationalize if it could be performed at all. Two mechanisms were proposed and now we know that even when the reaction should be quite exothermic, the reaction barriers are too high to be overcome by conventional methods. We now need to find a way to decrease those barriers (cue transition metal simulations). So in a way we are dealing here with the mechanism of a reaction that never happens (at least in an intramolecular way), leading to a reverse reductio ad absurdum reasoning – we assumed the reaction(s) did happen and we found out why is it impossible for them to happen.

No pic. available as of yet

Luis Enrique “Kike” Aguilar
Luis continues to work with calix(n)arenes, this lab’s first love, in drug delivery systems. He is working with two drugs at once: Bosutinib and Sorafenib, second generation drugs for the treatment of Chronic Myeloid Leukemia in cases were resistance to Imatinib has been developed. One of his main goals is to find a calixarene system which is able to discriminate between Bosutinib and pseudo-bosutinib, a commercial isomer which has incorrectly been available for a few years now.

"Kike" Aguilar -  Calix[n]arenes as drug carriers for Bosutinib and Sorafenib

“Kike” Aguilar – Calix[n]arenes as drug carriers for Bosutinib and Sorafenib

Thanks a lot for your efforts; they are paying good results to your ca

The boys from the lab

The boys from the lab

reers and the advancement of our research group. Now back to work, guys!



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