Category Archives: Research

Transition State Search (QST2 & QST3) and IRC with Gaussian09


Theoretical evaluation of a reaction mechanism is all about finding the right transition states (TS) but there are no guarantees within the available methods to actually find the one we need. Chemical intuition in the proposal of a mechanism is paramount. Let’s remember that a TS is a critical point on a Potential Energy Surface (PES) that is a minimum in every dimension but one. For a PES with more than two degrees of freedom, a hyper-surface, envisioning the location of a TS is a bit tricky, in the case of a three dimensional PES (two degrees of freedom) the saddle point constitutes the location of the TS as depicted in figure 1 by a section of a revolution hyperboloid.

400px-Saddle_point

Fig1. Saddle point on a surface (min in one direction; max in the other)

Fig 1a Pringles chips -Yuck-. They exhibit a maximum on the direction parallel to the screen and a minimum on the direction perpendicular to the screen at the same point.

Fig 1a Pringles chips -Yuck-. They exhibit a maximum on the direction parallel to the screen and a minimum on the direction perpendicular to the screen at the same point.

The following procedure considers gas phase calculations. Nevertheless, the use of the SCRF keyword activates the implicit solvent calculation of choice in order to evaluate to some degree the solvent influence on the reaction energetics at different temperatures with the use of the temperature keyword.

The first step consists of a high level optimization of all minimums involved, such as reagents, products and intermediates, with a subsequent frequency analysis that includes no imaginary eigenvalues.

In order to find the structures of the transition states we use in Gaussian the Synchronous Transit-guided Quasi-Newton method [1] through the keywords QST2 or QST3. In the former case, coordinates for the reagents and products are needed as input; for the latter keyword, coordinates for the TS structure guess is needed also.

QST2)

%chk=file.chk
%nprocshared=n
%mem=nGB

#p opt=(qst2,redundant) m062x/6-31++G(d,p) freq=noraman Temperature=373.15 SCRF=(Solvent=Water)

Title card for reagents

Q M
Cartesian Coordinates for reagents
blank line
Title card for products

Q M
Cartesian Coordinates for products
blank line

QST3)

%chk=file.chk
%nprocshared=n
%mem=nGB

#p opt=(qst3,redundant) m062x/6-31++G(d,p) freq=noraman Temperature=373.15 SCRF=(Solvent=Water)

Title Card for reagents

Q M
Cartesian Coordinates for reagents
blank line
Title card for products

Q M
Cartesian Coordinates for products
blank line–
Title card for TS
Q M
Cartesian Coordinates for TS
blank line

NOTE: It is fundamental that the numbering order is kept constant throughout the molecular specifications of all two, or three, input structures. Hence, I recommend to build a set of molecules, save their structure, and then modified the coordinates on the same file to produce the following structure, that way the number for every atom will remain the same for every step.

As I wrote above, there are no guarantees of finding the right TS so many attempts are probably needed. Once we have the optimized structures for all the species involved in our mechanistic proposal we can plot their energies very simply with MS Excel the way we’ve previously described in this blog (reblogged from eutactic.wordpress.com)

Once we’ve succeeded in finding the structure of our TS we may run an Internal Reaction Coordinate (IRC) calculation. This calculation will connect the TS structure to those of the products and the reagents. Initial constant forces are required and these are commonly retrieved from the TS calculation checkpoint file through the RCFC keyword.

%chk=QST3_2p.chk
%nprocshared=8

#p m062x/6-31++G(d,p) IRC=(Maxpoints=50,RCFC,phase=(2,1))Temperature=373.15 SCRF=(Solvent=Water) geom=allcheck

Title Card

Q M
blank line

Finally, the IRC path can be visualized with GaussView from the Results menu. A successful IRC will link both structures along a single reaction coordinate proving that both reagents and products are linked by the obtained TS.

Hat tip to Howard Diaz who has become quite skillful in calculating these mechanisms as proven by his recent poster at the XII RMFQT a couple of weeks back. And as usual thanks to everyone who reads, comments, likes, recommends, rates and shares my silly little posts.

Summer Internships


This week has been a happy one since four new additions to our staff have been made, at least for the summer, that is. Paulina, Eliana, Javier and Daniel have come to our lab from various different towns across the nation to spend six weeks working hard in small projects related to our lines of research; namely theoretical drug carriers design. This time the drug under study is known as GTP or 3-phenyl(1H-[1]benzofuro[3,2]pyrazole and calixarenes will once again act as the potential carriers.

20130626-122705.jpg

Left to Right: Daniel, Javier, Paulina and Eliana
(Summer Interns – 2013)

They all came as part of the Dolphin Research Summer Program (link in Spanish only) in which college students spend a few weeks doing research in the lab of their choosing. This is the first time I participate as a tutor and I find it a great opportunity for young students to get familiar with certain aspects of science they wont learn inside school.

So far these past three days have been quite intense with them learning how to edit and submit a Gaussian calculation in a Linux environment. I’ve already taught them about geometry optimizations, frequency analysis, (natural) population analysis and Fukui reactivity indices calculation. There is much more to learn still, of course, but so far so good. I believe the major drawback so far has been their own eagerness since they’d like to have all the data imediately! Unfortunately they’ll have to wait for their initial calculations to converge. We started this week by doing some simple analysis of all the properties described above for the Cytosine-Guanine base pair at the B97D/6-31+G(d,p) level of theory. Luckily their calculation crashed promptly, and I find that lucky because that gave me the opportunity to teach them how to relaunch a failed calculation, which, unfortunatelly will happen more often than not.

So, welcome guys! Thanks for choosing this lab for doing your internships. I hope you find our research interesting and motivating, may this be the first step into a full time research career. Also, kudos to the Dolphin Staff for helping promote science in young Mexican students. Stay tuned for a guest post from all of them once they finish their time here.

#RealTimeChem – Happy birthday DNA!


What a happy coincidence -if indeed it was- that #RealTimeChem week happened to coincide with the sixtieth anniversary of the three seminal papers published in Nature on this day back in 1953, one of which was co-authored by J. Watson and F. Crick; of course I mean the publication for the first time of the structure of deoxyribose nucleic acid, or DNA, as we now call it.

You can get the original Nature papers from 1953 here at: http://www.nature.com/nature/dna50/archive.html (costs may apply)

Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid 737

J. D. WATSON & F. H. C. CRICK
doi:10.1038/171737a0

Molecular Structure of Nucleic Acids: Molecular Structure of Deoxypentose Nucleic Acids 738
M. H. F. WILKINS, A. R. STOKES & H. R. WILSON
doi:10.1038/171738a0

Molecular Configuration in Sodium Thymonucleate 740
ROSALIND E. FRANKLIN & R. G. GOSLING
doi:10.1038/171740a0

Nature’s podcast released two episodes (called ‘pastcast’) to celebrate DNA’s structure’s birthday, one of them is an interview with Dr. Raymond Gosling who in 1953 worked under Dr. Rosalind Franklin at King’s College London in diffractometry of biological molecules. If you haven’t listened to them you can get them here at nature.com/nature/podcasts. Of course, the history around the discovery of DNA’s structure is not without controversy and it has been long argued that the work of Franklin and Gossling didn’t get all deserved credit from Watson and Crick. In their paper W&C acknowledge the contribution of the general nature of DNA from the unpublished results by Franklin’s laboratory but that is as far as they went, they didn’t even mention photo 51 which Crick saw at Wilkins laboratory, who in turn got it from Gossling at Franklin’s suggestion. Still, no one can deny that the helical structure with which we are now familiar is their work, and more importantly the discovery of the specific pairing, which according to Gossling was a stroke of genious that probably couldn’t have happened in his own group, but without Franklin’s diffraction and Gossling’s crystallization  there was little they could do. Details about the process used to crystallize DNA can be heard in the aforementioned podcast, along with an inspiring tale of hard work by Dr. Gossling. Go now and listen to it, its truly inspiring.

For me it was not the story of a helix, that I was familiar with; it was the story of the specific pairing of two hélices
– Dr. Raymond Gosling

Famous Photo 51 by Dr. Rosalind Franklin and Raymond Gosling (Source: Wikipedia)

The iconic Photo 51 by Dr. Rosalind Franklin and Raymond Gosling (Source: Wikipedia)

Above, the iconic Photo 51 taken by Franklin and Gossling (have you ever noticed how most scientists refer to Franklin just as Rosalind but no one refers to Watson as James? Gender bias has a role in this tale too) To a trained crystallographer, the helical symmetry is evident from the diffraction pattern but going from Photo 51 to the representation below was the subject of hard work too.

Modern DNA representation (Source: Wikipedia)

Modern DNA representation (Source: Wikipedia)

There are million of pages written during the last 60 years about DNA’s structure and its role in the chemistry of life; the nature of the pairing and the selectivity of base pairs through hydrogen bond interactions, an interaction found ubiquitously in nature; water itself is a liquid due to the intermolecular hydrogen-bonds, which reminds us about the delicate balance of forces in biochemistry making life a delicate matter. But I digress. Millions of pages have been written and I’m no position of adding a meaningful sentence to them; however, it is a fascinating tale that has shaped the course of mankind, just think of the Human Genome Project and all the possibilities both positive and negative! DNA and its discovery tale will continue to amaze us and inspire us, just like in 2011 it inspired the Genetech company to set a Guiness World Record with the largest human DNA helix.

Genetech SF, Cal. USA (Source worldrecordacademy.com)

Genetech SF, Cal. USA (Source worldrecordacademy.com)

Happy birthday, DNA!

XIth Mexican Reunion on Theoretical Physical Chemistry


For over a decade these meetings have gathered theoretical chemists every year to share and comment their current work and to also give students the opportunity to interact with experienced researchers, some of which in turn were even students of Prof. Robert Parr, Prof. Richard Bader or Prof. Per Olov Löwdin. This year the Mexican Meeting on Theoretical Physical Chemistry took place last weekend in Toluca, where CCIQS is located. You can find links to this and previous meetings here. We participated with a poster which is presented below (in Spanish, sorry) about our current research on the development of calixarenes and tia-calixarenes as drug carriers. In this particular case, we presented our study with the drug IMATINIB (Gleevec as branded by Novartis), a powerful tyrosinkynase inhibitor widely employed in the treatment of Leukaemia.

The International Journal of Quantum Chemistry is dedicating an issue to this reunion. As always, this meeting posed a great opportunity to reconnect with old friends, teachers, and colleagues as well as to make new acquaintances; my favourite session is still the beer session after all the seminars! Kudos to María Eugenia “Maru”  Sandoval-Salinas for this poster and the positive response it generated.

CONACyT funding was approved!


A couple of months ago, maybe a little bit more, I got the news that the project I submitted to the National Council for Science and Technology (CONACyT) was approved! Now we only have to wait for the money to actually show up and that might take a while – a long while! Nevertheless this is always very good news and we are very excited about it because this means more money for research, specifically on the electronic molecular pathways of photosynthesis.

When I submitted the project I wrote a little post about the funding scheme which seemed, if not unfair, at least flawed, and I still believe in what I wrote. To be honest I thought it wouldn’t be funded but it turns out it was but I still think the reviewing process could be better.

There is a lot of research to do – too little time to do it.

Institute of Chemistry Library flood – UNAM


If a mind is a terrible thing to waste, then wasting a collective mind is an even more terrible thing. During the past weekend the library at the institute of chemistry suffered a flood caused by a broken pipe just above it, which incidentally happens to be the lab were I used to work as an undergrad student. When it comes to scientific journals, our institute still relies a lot on paper issues for the oldest numbers; we can order them online but it’s just easier to Xerox it at the library if you really need to read that old reference.

This morning the librarians were appalled when noticed not only the huge puddle on the floor but all the books and scientific journals that were dripping water from the shelves. The broken pipe has been fixed and the water on the floor has been mopped. It is now the books the ones that suffer the aftermath of this accident. Not only saving the information was important; wet paper is a great culture media for fungi which in turn could pose a health threat to all users. The administrative staff immediately got to work in recruiting academics and students to help the drying process: “Heal a book!“, they informally called it. Everyone grabbed an item and with the help of industrial blow dryers – the kind we use in chemistry labs to dry wet glassware – and an extraordinary amount of paper towels, each person got to dry the journals page by page.

I got an item that corresponded to the British journal New Scientist, which consisted of about fifteen issues from the year 1980. When I noticed the title in my hand I wanted to switch it. Should we save first those journals with the highest impact factor? or should we work on those that are most relevant to our own research? Should we throw away Chemical Abstracts now that the whole database is online? After all, New Scientist is a magazine which summarizes research that has already been peer reviewed and published; it is journalistic work, not peer reviewed science. But I was afraid to look pedantic so I got to work on drying it.

Kudos to the library staff on organizing in promptu “Heal a book!”

Students as well as the academic and administrative staff drying journals

Each person had their own technique. Some journals had their binding covers still in good shape so they were placed open standing on the floor in front of fans. Some placed paper towels carefully between pages and after a while they would remove them and then use the blow dryer. I thought that if I heated the edges of the paper and thus dried them, capillarity would drive the moisture in the innermost part of each page outwards. Didn’t quite work, at least not in a pragmatic time scale, so I went back to page by page.

I’m glad I did so. That way I was able to find some real pieces of history which could make any scientist nostalgic. For example: I took these photos with my iPod, and if you are by any chance reading this piece on an iPhone, you must find the following  picture about Swedish research endearing.

An ancient iPad or an edgy ‘Etch-a-Sketch‘?

Yes, online doodling games were already a thought back in 1980!

Are you subscribed to this blog? That means you got a notification by e-mail. So what? No big deal! Well, back in 1980 Britain was getting excited over a new form of comunication called the ‘Electronic Mail’ (available only at a couple of post offices). Besides, you wouldn’t have been able to get that message nor read this post on an HP Matrix Machine (you can’t even find a decent link in google about it nowadays!)

But scientists are not all about working, we like games too! So how about purchasing a ‘Hungarian Magic Cube‘ or a ‘Chess Computer‘?

An 80’s sensation!

E-chess

We also love a juicy piece of gossip. For instance, did you know that John Maddox was a controversial editor for Nature back in the 70’s who, as a student, went into chemistry because if he’d gone into physics he could’ve been drafted by the army in WWII to work on radars? Well me neither. But it seems that we should have known who he was, and now we do.

Sir John Maddox

There were many pieces of science news that nearly kept me in the library all night, if not for the fact that I had to drive 50 miles from Mexico City to my place in Toluca, but the one that captured my attention more than any other was the news of a European dream envisioned more than three decades ago; a dream from a group of scientists about looking for answers, like any other group of scientists, answers that are fundamental for the understanding of our universe and the understanding of matter, back when some of the biggest questions hadn’t even been fully posed, this group of visionaries agreed on taking the necessary steps to build an enormous subatomic-particle Supercollider for the European Center for Nuclear Research, better known as CERN.

The announcement of grand things to come

Back in 1980 I was already alive but I was only two years old. I could barely talk and had no idea what the word ‘future‘ meant, let alone what I’d become when it reached me. Now, even if I’m not a particle physicist I get excited about the news regarding the finding of the Higgs Boson and even if I’m not an astronomer I also get excited about pictures from the Curiosity Rover on Mars. I am a scientist. One out of hundreds of thousands or perhaps even millions, and this is part of my collective memory, the memory of the work of those who paved the road for us, those giants upon whose shoulders we struggle day by day to stand with dignity and against all odds. But here is the thing: those giants are actually made of dwarfs, millions of them; millions of us. Thousands and thousands of papers written, reviewed and published; papers that collectively gather the scientific experience summed up in rigorous experiments both successful and failed.

Preserving the information in those wet journals is important despite the fact you can get them all online. I hope one day a bored chemistry grad student goes to the library and browses old issues of New Scientist and other journals just for fun; they’ll go for a trip down a collective Memory Lane which will remind them that if they can dream it in the present, they can make it come true in the future.

100,000 visitors!


This morning at around 9 AM, I guess, this little blog of mine reached a significant milestone: It reached 100,000 visitors!

The blog started about 3.5 years ago when I was still living in Romania working at the lab of the late Prof. Dr. Ioan Silaghi-Dumitrescu. Back then I started the blog as a way to make my research visible to others and maybe in that way I could gain some notoriety which could help me in the near future to land a fine research position. None of that happened. I remember we were having some issues with some PCM calculations in the lab and after a lot of hard work and a lot of asking we gather some tips to work with implicit solvation models in Gaussian. Prof. Silaghi suggested we should write them down and put them on the wall of the lab so we had them available at all times; it was then when I suggested we could place them in my little blog so we had them available online. This happened in September 2009, three years ago, and little did I know, this post became quite popular, it is still one of the most visited ones in the blog. Later on we had a similar problem while trying to visualize Natural Bond Orbitals, there was too much information but it was all scattered, so we did it again, we gathered some of the info and made a new post which became also quite popular.

100,012 visitors this morning. Thanks!

Little have I written about my own work, mostly because of fear of being scooped, I guess.

I’d like to thank every reader who has ever liked, commented, rated, favorited, shared, reblogged, blogrolled, recommended any of my posts and the nearly 200 people who have subscribed or followed this little blog, as I like to call it.

The Local Bond Order, LBO (Barroso et al. 2004)


I don’t know why I haven’t written about the Local Bond Order (LBO) before! And a few days ago when I thought about it my immediate reaction was to shy away from it since it would constitute a blatant self-promotion attempt; but hell! this is my blog! A place I’ve created for my blatant self-promotion! So without further ado, I hereby present to you one of my own original contributions to Theoretical Chemistry.

During the course of my graduate years I grew interested in weakly bonded inorganic systems, namely those with secondary interactions in bidentate ligands such as xanthates, dithiocarboxylates, dithiocarbamates and so on. Description of the resulting geometries around the central metallic atom involved the invocation of secondary interactions defined purely by geometrical parameters (Alcock, 1972) in which these were defined as present if the interatomic distance was longer than the sum of their covalent radii and yet smaller than the sum of their van der Waals radii. This definition is subject to a lot of constrictions such as the accuracy of the measurement, which in turn is related to the quality of the monocrystal used in the X-ray difraction experiment; the used definition of covalent radii (Pauling, Bondi, etc.); and most importantly, it doesn’t shed light on the roles of crystal packing, intermolecular contacts, and the energetics of the interaction.

This is why in 2004 we developed a simple yet useful definition of bond order which could account for a single molecule in vacuo the strength and relevance of the secondary interaction, relative to the well defined covalent bonds.

Barroso-Flores, J. et al. Journal of Organometallic Chemistry 689 (2004) 2096–2102
http://dx.doi.org/10.1016/j.jorganchem.2004.03.035,

Let a Molecular Orbital be defined as a wavefunction ψi which in turn may be constructed by a linear combination of Atomic Orbitals (or atom centered basis set functions) φj

We define ζLBO in the following way, where we explicitly take into account a doubly occupied orbital (hence the multiplication by 2) and therefore we are assuming a closed shell configuration in the Restricted formalism.

The summation is carried over all the orbitals which belong to atom A1 and those of atom A2.
Simplifying we yield,

where Sjk is the overlap integral for the φj and φk functions.

By summing over all i MOs we have accomplished with this definition to project all the MO’s onto the space of those functions centered on atoms A1 and A2. This definition is purely quantum mechanical in nature and is independent from any geometric requirement of such interacting atoms (i.e. interatomic distance) thus can be used as a complement to the internuclear distance argument to assess the interaction between them. This definition also results very simple and easy to calculate for all you need are the coefficients to the LCAO expansion and the respective overlap integrals.

Unfortunately, the Local Bond Order hasn’t found much echo, partly due to the fact that it is hidden in a missapropriate journal. I hope someone finds it interesting and useful; if so, don’t forget to cite it appropriately 😉

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