Category Archives: calixarenes
Last Friday we had a new graduate student when our very own Marco Antonio Diaz defended his BSc thesis on the in silico design of drug carriers based on calix[n]arenes. During his thesis he performed around 160 different calculations regarding the interaction energy of our host-guest inclusion complexes, both using the supramolecular method and the NBODel procedure available in NBO3.1 as provided with Gaussian 09. One of the main targets of this work was to assess both methods -with the proper BSSE corrections- in their capabilities for the calculation of interaction energies.
We found that the NBODel method consistently generates interaction energies that are similar to those of the SM method + the BSSE correction (as opposed to SM – BSSE which is the proper correction). Marco and I are still in the process of writing the article so maybe it will be published in early 2018. In this case we’re using calixarenes to deliver three drugs: warfarine, furosemide, phenylbutazone to compite with ocratoxin-A (OTA) for the binding site in Human Serum Albumin (HSA).
This project is undertaken in collaboration with my good friend Dr. Sándor Kunsági-Máté in Pécsi Tudomanyegyetem in Hungary.
Congratulations to Marco from all of us here at the lab!
For the fifth year in a row my research group has participated in this traditional meeting on theoretical and computational chemistry, now at the beautiful city of Merida in southeastern Mexico.
Several distinguished international guests included Profs. Jose Luis Mendoza (Florida State University), Adrián Roitberg (University of Florida), Vincent Ortiz (Auburn University) and Paul Ayers (McMaster U. Canada); Their contributions rounded up nicely those of household names like Drs. Alberto Vela, Gabriel Merino (CINVESTAV) (the latter was also the main organizer), Jesus Hernández-Trujillo (UNAM), Jose Luis Gazquez (UAM-I), Óscar Jimenez (Guanajuato), and so many others who were also present.
My students presented four posters summarized below:
1) Maru Sandoval and Gustavo Mondragón on Photosynthesis, particularly the search for exciton transference mechanisms in both natural and theoretical arrangements of photosynthetic pigments. Some very exciting results have been observed; their publication is really near.
2) Raúl Torres and Gustavo Mondragón presented their work on arsenic removing calixarenes, published earlier this year, and the extension of said work to As(III) acids. Graphene oxide is now considered in our simulations as per the experimental work of our colleagues, Prof. Reyes Sierra and Prof. Eddie Lopez-Honorato.
3) Marco Diaz, Guillermo Caballero, Gustavo Mondragón and Raúl Torres had this poster on the calculation of sigma holes as descriptors for predicting pka values in organic acids. Their +1600 calculations project has found the best levels of theory (and ruled out some like B3LYP, of course) with some nice correlations. Yet, much work is still to be done but we’re on the right track.
4) Durbis Castillo presented his work on molecular docking and dynamics of a large library of HIV-1 entry inhibitors for which he uses the suite MAESTRO as a continuation of another project of ours. His enormous library is now in the hundredths of thousands and although we’re facing some technical difficulties, Durbis is thriving in his search. This is our first serious attempt towards a more mature drug discovery project; a manuscript should be ready in the first part of next year.
This guys and the rest of the lab who weren’t present are the ones who make our research flourish and they’ve all earned a day or two at the beach!
Here’s to fifteen more years of RMFQT!
With pleasure I announce that last week our very own Gustavo “Gus” Mondragón became the fifth undergraduate student from my lab to defend his BSc thesis and it has to be said that he did it admirably so.
Gus has been working with us for about a year now and during this time he not only worked on his thesis calculating excited states for bacteriochlorophyl pigments but also helped us finishing some series of calculations on calix[n]arene complexes of Arsenic (V) acids, which granted him the possibility to apear as a co-author of the manuscript recently published in JIPH. Back in that study he calculated the interaction energies between a family of calix macrocycles and arsenic acid derivatives in order to develop a suitable extracting agent.
For his BSc thesis, Gus reproduced the UV-Vis absorption spectra of bacteriochlorophyll-a pigments found in the Fenna-Matthews-Olson complex of photosynthetic purple bacteria using Time Dependent Density Functional Theory (TD-DFT) with various levels of theory, with PBEPBE yielding the best results among the tried set. These calculations were performed at the crystallographic conformation and at the optimized structure, also, in vacuo results were compared to those in implicit solvent (SMD, MeOH). He will now move towards his masters where he will further continue our research on photosynthesis.
Thank you, Gustavo, for your hard work and your sense of humor. Congratulations on this step and may many more successes come your way.
As part of an ongoing collaboration with the University of Arizona (UA) and the Center for Advanced Research and Studies (CINVESTAV – Saltillo), we are looking into the use of calix[n]arenes for bio-remediation agents capable to extract Arsenic (V) and (III) species from water. Water contamination by arsenic is a pressing issue in northern Mexico and the southern US, therefore any efforts aiming to their elimination has strong social and health repercussions.
As in previous studies, all calixarenes were optimized along with their corresponding guests within the cavity, namely H3AsO4, H2AsO4– and HAsO42- at the DFT level with the so-called Minnesota functionals by Truhlar and Cao, M06-2X/6-31G(d,p) level of theory. Interaction energies were calculated through the NBODel procedure. Calixarenes with R = SO3H and PO3H are the most promising leads. This study is now publishes in the Journal of Inclusion Phenomena and Macrocyclic Chemistry (DOI 10.1007/s10847-016-0617-0) as an online first article.
This article is also the first to be published by our undergraduate (and almost grad student in a month) Gustavo Mondragón who took this project on a side to his own research on photosynthesis.
Now my colleagues in Arizona and Saltillo, Prof. Reyes Sierra and Dr. Eddie López, respectively, will work on the experimental side of the project. Further calculations are being undertaken to extend this study to As(III) and to the use of other potential extracting materials such as metallic nanoparticles to which calixarenes could be covalently linked.
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.
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!
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.
I always get very happy to have a new paper out there! I find it exciting but most of all liberating since it makes you feel like your work is going somewhere but most of all that it is making its way ‘out there’; there is a strong feeling of validation, I guess.
Two very different families of calix[n]arenes (Fig 1) were tested as drug carriers for a very small molecule with a huge potential as a chemotherapeutic agent against Leukemia, namely, 3-phenyl-1H-benzofuro[3,2-c]pyrazole a.k.a. GTP which has proven to be an effective in vitro Tyrosine Kinase III inhibitor. Having such a low molecular weight it is expected to have a very high excretion rate therefore the use of a carrier could increase its retention time and hence its activity. This time we considered n = 4, 5, 6 and 8 for the size of the cavities and R = -SO3H and -OEt as functional groups on the upper rim as to evaluate only a polar coordinating group and a non-polar non-coordinating one since GTP offers two H-bond acceptor sites and one H-bond donor one along the π electron density that could form π – π stacking interactions between the aromatic groups on GTP and the walls of the calixarene.
Once again calculations were carried out at the B97D/6-31G(d,p) level of theory along with molecular dynamics simulations for over 100 ns of production runs. NBO Deletion interaction energies were computed in order to discern which hosts formed the most stable complexes.
You may find a link to the ScienceDirect website for downloading the paper from this link. Last, but certainly not least, I’d like to thank all coauthors for their contributions and patience in getting this study published: Dr. Rodrigo Galindo-Murillo; Alberto Olmedo-Romero; Eduardo Cruz-Flores; Dr. Petronela M. Petrar and Prof. Dr. Kunsági-Máté Sándor. Thanks a lot for everything!