Pauli’s Exclusion Principle is a paramount concept in Quantum Mechanics which has implications from statistical mechanics to quantum chemistry, consequently, there are many different statements to summarize it depending on the forum. I occasionally joke with my students about how we learnt it in kindergarten an how we state it now at the end of our computational chemistry course.
So, are you a toddler or high up there with W. Pauli predicting the existence of sub-atomic particles at CERN? Which statement of Pauli’s Exclusion Principle sounds more familiar to you?
LOL just feeling a little humorous this morning!
As we approach to the end of another year, and with that the time where my office becomes covered with post-it notes so as to find my way back into work after the holidays, we celebrate another paper published! This time at the Journal of Physical Chemistry A as a follow up to this other paper published last year on JPC-C. Back then we reported the development of a selective sensor for Hg(II); this sensor consisted on 1-amino-8-naphthol-3,6-disulphonic acid (H-Acid) covalently bound to a modified silica SBA-15 surface. H-Acid is fluorescent and we took advantage of the fact that, when in the presence of Hg(II) in aqueous media, its fluorescence is quenched but not with other ions, even with closely related ions such as Zn(II) and Cd(II). In this new report we delve into the electronic reasons behind the quenching process by calculating the most important electronic transitions with the framework laid by the Time Dependent Density Functional Theory (TD-DFT) at the PBE0/cc-pVQZ level of theory (we also included an electron core potential on the heavy metal atoms in order to decrease the time of each calculation). One of the things I personally liked about this work is the combination of different techniques that were used to assess the photochemical phenomenon at hand; some of those techniques included calculation of various bond orders (Mayer, Fuzzy, Wiberg, delocalization indexes), time dependent DFT and charge transfer delocalizations. Although we calculated all these various different descriptors to account for changes in the electronic structure of the ligand which lead to the fluorescence quenching, only delocalization indexes as calculated with QTAIM were used to draw conclusion, while the rest are collected in the SI section.
Thanks a lot to my good friend and collaborator Dr. Pezhman Zarabadi-Poor for all his work, interest and insight into the rationalization of this phenomenon. This is our second paper published together. By the way, if any of you readers is aware of a way to finance a postdoc stay for Pezhman here at our lab, please send us a message because right now funding is scarce and we’d love to keep bringing you many more interesting papers.
For our research group this was the fourth paper published during 2014. We can only hope (and work hard) to have at least five next year without compromising their quality. I’m setting the goal to be 6 papers; we’ll see in a year if we delivered or not.
I’d like to also take this opportunity to thank all the readers of this little blog of mine for your visits and your live demonstrations of appreciation at various local and global meetings such as the ACS meeting in San Francisco and WATOC14 in Chile, it means a lot to me to know that the things I write are read; if I were to make any New Year’s resolutions it would be to reply quicker to questions posted because if you took the time to write I should take the time to reply.
I wish you all the best for 2015 in and out of the lab!
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.
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.
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.
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.
reers and the advancement of our research group. Now back to work, guys!
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.
(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.
Select your WFN/WFX file on which the calculation is to be run. (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).
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).
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.
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!
If you made it this far, let me tell you that this is also available at Slideshare.com :)
Thanks for reading, commenting and sharing!
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.
This is my first time giving a talk at the ACS meeting so I’m a tad nervous but also excited about the possibility to listen to so many great researchers and hopefully interact with some of them, although such a massive event is hardly the best place to build a network.
My talk will deal with our recently published work on calixarene based drug carriers and the new results we are currently getting, and will take place on Tuesday 12th at 16:15 at the session regarding the use of small macrocycles in drug discovery. Feedback is very important to us so we look forward to some heavy criticism of our results.
If you are there, download the free app which will show you around the different presentations and stands.
Well, I only contributed with the theoretical section by doing electronic structure calculations, so it isn’t really a paper we can ascribe to this particular lab, however it is really nice to see my name in JACS along such a prominent researcher as Prof. Chad Mirkin from Northwestern University, in a work closely related to my area of research interest as macrocyclic recognition agents.
In this manuscript, a calixarene is allosterically opened and closed reversibly by coordinating different kinds of ligands to a platinum center linked to the macrocycle. (This approach has been referred to as the weak link approach.) I recently visited Northwestern and had a great time with José Mendez-Arroyo, the first author, who showed me around and opened the possibility for further work between our research groups.
Closed, semi-open and fully open conformations; selectivity is modulated through cavity size. (Ligands: Green = Chloride; Blue = Cyanide)
Here at UNAM we calculated the interaction energies for the two guests that were successfully inserted into the cavity: N-methyl-pyridinium (Eint = 57.4 kcal/mol) and Pyridine-N-oxide (Eint = +200.0 kcal/mol). Below you can see the electrostatic potential mapped onto the electron density isosurface for one of the adducts. Relative orientation of the hosts within the cavity follows the expected (anti-) alignment of mutual dipole moments. At this level of theory, we could easily be inclined to assert that the most stable interaction is indeed the one from the semi-open compound and that this in turn is due to the fact that host and guest are packed closer together but there is also an orbital issue: Pyridine Oxide is a better electron acceptor than N-Me-pyridinium and when we take a closer look to the (Natural Bonding) orbitals interacting it becomes evident that a closer location does not necessarily yields a stronger interaction when the electron accepting power of the ligand is weaker (which is, in my opinion, both logic and at the same time a bit counterintuitive, yet fascinating, nonetheless).
All calculations were performed at the B97D/LANL2DZ level of theory with the use of Gaussian09 and NBO3.1 as provided within the former. Computing time at UNAM’s supercomputer known as ‘Miztli‘ is fully acknowledged.
The full citation follows:
A Multi-State, Allosterically-Regulated Molecular Receptor With Switchable Selectivity
Jose Mendez-Arroyo †, Joaquín Barroso-Flores §,Alejo M. Lifschitz †, Amy A. Sarjeant †, Charlotte L. Stern †, and Chad A. Mirkin *†
Thanks to José Mendez-Arroyo for contacting me and giving me the opportunity to collaborate with his research; I’m sure this is the first of many joint projects that will mutually benefit our groups.
Just as last year, the “Dolphin Summer Internship Program” (Programa Delfín) has started and this time it coincided with #RealTimeChem week. Four students from various cities (and accents) around Mexico have come to our lab in Toluca in order to spend about 7 weeks of research in the field of molecular modeling and within our research of molecular recognition in biochemistry. Karen, Cynthia, Jesús and Marco have started their training today as they arrived to CCIQS so we went over the (very) basics of quantum chemistry, the (very) basics of Linux and the basics of Gaussian09. (I should really think about developing some web tutorials or something because this impromptu training is very exhausting!)
Their academic backgrounds are mostly centered around pharmaceutics and biochemistry although their ages range from the second to the fourth year of college education. Computational chemistry is pretty unknown to all of them; I’ll do my best to change that, while at the same time I make them aware of its power as a research tool and as a research field in itself.
Here is to a very productive summer! I hope we manage to get enough data for a paper and, more importantly, that they all get a good experience out of their time here, make new friends and learn something new that enriches their skills in this increasingly competitive world.