#MemeYourThesis #MemeYourResearch


As we were hanging out recently, the idea came to us at the lab to create memes in order to summarize our work. We should be writing articles but hey, we needed the break, and so we shared them with each other in our last group meeting along with a good laugh. Here are some of the funniest ones.

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A fail safe method for Comp. Chem.

Having doughnuts during our weekly meetings has proven a huge success in itself:

Screenshot_16cerebro3 ING

Finding transition states for organic chemical reactions can be a bit frustrating at times:

Screenshot_19Screenshot_18

Good old photosynthesis sparked a few realizations too:

We’re dealing with docking calculations for a massive number of molecules. This has sparked a few inside jokes too:

 

A conversation about heterocyclic nomenclature that sparked this other post:

1xej3h

Try your own and share. Thanks for reading.

 

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A New Graduate Student!


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).

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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!

The Evolution of Photosynthesis


Recently, the journal ACS Central Science asked me to write a viewpoint for their First Reactions section about a research article by Prof. Alán Aspuru-Guzik from Harvard University on the evolution of the Fenna-Matthews-Olson (FMO) complex. It was a very rewarding experience to write this piece since we are very close to having our own work on FMO published as well (stay tuned!). The FMO complex remains a great research opportunity for understanding photosynthesis and thus the origin of life itself.

In said article, Aspuru-Guzik’s team climbed their way up a computationally generated phylogenetic tree for the FMO from different green sulfur bacteria by creating small successive mutations on the protein at a time while also calculating their photochemical properties. The idea is pretty simple and brilliant: perform a series of “educated guesses” on the structure of FMO’s ancestors (there are no fossil records of FMO so this ‘educated guesses’ are the next best thing) and find at what point the photochemistry goes awry. In the end the question is which led the way? did the photochemistry led the way of the evolution of FMO or did the evolution of FMO led to improved photochemistry?

Since both the article and viewpoint are both published as open access by the ACS, I wont take too much space here re-writing the whole thing and will instead exhort you to read them both.

Thanks for doing so!

Chemistry Makes the Chemical


The compound shown below in figure 1 is listed by Aldrich as 4,5,6,7-tetrahydroindole, but is it really?

tetrahydroindole

Fig 1. An indole?

To a hardcore organic chemist it is clear that this is not an indole but a pyrrole because  the lack of aromaticity in the fused ring gives this molecule the same reactivity as 2,3-diethyl pyrrole.  If you search the ChemSpider database for ‘tetrahydroindole’ the search returns the following compound with the identical chemical formula C8H11N but with a different hydrogenation pattern: 2,3,3a,4-Tetrahydro-1H-indole

14650657

Fig 2. Also listed as an indole

The real indole, upon an electrophilic attack, behaves as a free enamine yielding the product shown in figure 3 in which the substitution occurs in position 3. This compound cannot undergo an Aromatic Electrophilic Susbstitution since that would imply the formation of a sigma complex which would disrupt the aromaticity.

indole_reaction

On the contrary, the corresponding pyrrole is substituted in position 2

pyrole_reaction

These differences in reactivity towards electrophiles are easily rationalized when we plot their HOMO orbitals (calculated at the M062X/def2TZVP level of theory):

If we calculate the Fukui indexes at the same level of theory we get the highest value for susceptibility towards an electrophilic attack as follows: 0.20 for C(3) in indole and 0.25 for C(2) in pyrrole, consistent with the previous reaction schemes.

So, why is it listed as an indole? why would anyone search for it under that name? Nobody thinks about cyclohexane as 1,3,5-trihydrobenzene. According to my good friend and colleague Dr. Moisés Romero most names for heterocyles are kept even after such dramatic chemical changes due to historical and mnemonic reasons even when the reactivity is entirely different. This is only a nomenclature issue that we have inherited from the times of Hantzsch more than a century ago. We’ve become used to keeping the trivial (or should I say arbitrary) names and further use them as derivations but this could pose an epistemological problem if students cannot recognize which heterocycle presents which reactivity.

So, in a nutshell:

Chemistry makes the chemical and not the structure.

A thing we all know but sometimes is overlooked for the sake of simplicity.

Mexico City Earthquake


Mexico City took a hard earthquake just a couple of weeks after the southern part of the country had another and 32 years to the day after the big one back in 1985 (I was seven back then).

If you wanna help this is a great place to do so. The Topos (Moles) Brigade is an elite rescue team that is taking out people from the rubble not just during this disaster but anywhere in the world where they’re needed.

Thanks

WATOC 2017


Last week the WATOC congress in Munich was a lot of fun. Our poster on photosynthesis had a great turnout and got a lot of positive feedback as well as many thought provoking questions. One of the highlights of my time there was seeing my former students and knowing they’re all leading successful and happy grad-student lives in Europe, I’m so very proud of them. It was great to connect with old friends and making new ones; a big thank you to all the readers of this little blog who took the time to come and say hi, I’m very glad the blog has been helpful to you.

Better recounts of WATOC 2017 can be found in the great Rzepa’s blog here and here.

Below there is an image of our poster (some typos persist).

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See you all in 2020!

Photosynthesis and Singlet Fission – #WATOC2017 PO1-296


If you work in the field of photovoltaics or polyacene photochemistry, then you are probably aware of the Singlet Fission (SF) phenomenon. SF can be broadly described as the process where an excited singlet state decays to a couple of degenerate coupled triplet states (via a multiexcitonic state) with roughly half the energy of the original singlet state, which in principle could be centered in two neighboring molecules; this generates two holes with a single photon, i.e. twice the current albeit at half the voltage (Fig 1).

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Jablonski’s Diagram for SF

It could also be viewed as the inverse process to triplet-triplet annihilation. An important requirement for SF is that the two triplets to which the singlet decays must be coupled in a 1(TT) state, otherwise the process is spin-forbidden. Unfortunately (from a computational perspective) this also means that the 3(TT) and 5(TT) states are present and should be taken into account, and when it comes to chlorophyll derivatives the task quickly scales.

SF has been observed in polyacenes but so far the only photosynthetic pigments that have proven to exhibit SF are some carotene derivatives; so what about chlorophyll derivatives? For a -very- long time now, we have explored the possibility of finding a naturally-occurring, chlorophyll-based, photosynthetic system in which SF could be possible.

But first things first; The methodology: It was soon enough clear, from María Eugenia Sandoval’s MSc thesis, that TD-DFT wasn’t going to be enough to capture the whole description of the coupled states which give rise to SF. It was then that we started our collaboration with SF expert, Prof. David Casanova from the Basque Country University at Donostia, who suggested the use of Restricted Active Space – Spin Flip in order to account properly for the spin change during decay of the singlet excited state. A set of optimized bacteriochlorophyll-a molecules (BChl-a) were oriented ad-hoc so their Qy transition dipole moments were either parallel or perpendicular; the rate to which SF could be in principle present yielded that both molecules should be in a parallel Qy dipole moments configuration. When translated to a naturally-occurring system we sought in two systems: The Fenna-Matthews-Olson complex (FMO) containing 7 BChl-a molecules and a chlorosome from a mutant photosynthetic bacteria made up of 600 Bchl-d molecules (Fig 2). The FMO complex is a trimeric pigment-protein complex which lies between the antennae complex and the reaction center in green sulfur dependent photosynthetic bacteria such as P. aestuarii or C. tepidium, serving thus as a molecular wire in which is known that the excitonic transfer occurs with quantum coherence, i.e. virtually no energy loss which led us to believe SF could be an operating mechanism. So far it seems it is not present. However, for a crystallographic BChl-d dimer present in the chlorosome it could actually occur even when in competition with fluorescence.

FMO

FMO Complex. Trimer (left), monomer (center), pigments (right)

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BChQRU chlorosome. 600 Bchl-d molecules

I will keep on blogging more -numerical and computational- details about these results and hopefully about its publication but for now I will wrap this post by giving credit where credit is due: This whole project has been tackled by our former lab member María Eugenia “Maru” Sandoval and Gustavo Mondragón. Finally, after much struggle, we are presenting our results at WATOC 2017 next week on Monday 28th at poster session 01 (PO1-296), so please stop by to say hi and comment on our work so we can improve it and bring it home!

A New Graduate Student – Medicinal #CompChem on HIV-1


Last Friday Durbis Castillo-Pazos became officially a graduated chemist. His presentation about the in silico development of entry inhibtors  for the HIV-1 virus was very clear and straightforward and he performed admirably during the examination for which he graduated with Honors from the Mexico State Autonomous University (UAEMex).

Ever since he came to my lab, Durbis was adamant to work in some project related to medicinal chemistry which is not really my thing. Still, we were able to take an old project related to the in silico design of entry inhibitors for the protein GP120 which is responsible for the entry of the HIV-1 virus into human T-cells; the very first stage of the HIV infection which leads to AIDS. The lengths to which Durbis took the project were remarkable but none of that would have been possible without the leadership of my good friend and colleague Dr. Antonio Romo from the Queretaro Autonomous University (UAQ) who not only guided us through the nuances of the field but also on the intricacies of working with Schrödinger Inc.’s software, MAESTRO.

Suffice it to say that based on a piperazine core and four thousand fragments with commercial pharmaceutical applications, Durbis built a 16.3 million compounds library from which a few candidates are selected as potential drug molecules after several docking steps at various precision levels and molecular dynamics simulations plus QSAR related analysis. More about the details in future posts.

The knowledge gained by Durbis allowed him to become a member of the QSAR team led by Dr. Karina Martinez, at the Institute of Chemistry UNAM which provides QSAR studies to various companies who want to submit this kind of studies for regulatory purposes. Durbis has his sight abroad and has been admitted to a prestigious graduate program where he will keep seeking to improve his knowledge on medicinal chemistry. I’m sure he will succeed in anything on which he sets his mind.

Collaborations in Inorganic Chemistry


I began my path in computational chemistry while I still was an undergraduate student, working on my thesis under professor Cea at unam, synthesizing main group complexes with sulfur containing ligands. Quite a mouthful, I know. Therefore my first calculations dealt with obtaining Bond indexed for bidentate ligands bonded to tin, antimony and even arsenic; yes! I worked with arsenic once! Happily, I keep a tight bond (pun intended) with inorganic chemists and the recent two papers published with the group of Prof. Mónica Moya are proof of that.

In the first paper, cyclic metallaborates were formed with Ga and Al but when a cycle of a given size formed with one it didn’t with the other (fig 1), so I calculated the relative energies of both analogues while compensating for the change in the number of electrons with the following equation:

Fig 1

Imagen1

Under the same conditions 6-membered rings were formed  with Ga but not with Al and 8-membered rings were obtained for Al but not for Ga. Differences in their covalent radii alone couldn’t account for this fact.

ΔE = E(MnBxOy) – nEM + nEM’ – E(M’nBxOy)                     Eq 1

A seamless substitution would imply ΔE = 0 when changing from M to M’

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Hipothetical compounds optimized at the B3LYP/6-31G(d,p) level of theory

The calculated ΔE were: ΔE(3/3′) = -81.38 kcal/mol; ΔE(4/4′) = 40.61 kcal/mol; ΔE(5/5′) = 70.98 kcal/mol

In all, the increased stability and higher covalent character of the Ga-O-Ga unit compared to that of the Al analogue favors the formation of different sized rings.

Additionally, a free energy change analysis was performed to assess the relative stability between compounds. Changes in free energy can be obtained easily from the thermochemistry section in the FREQ calculation from Gaussian.

This paper is published in Inorganic Chemistry under the following citation: Erandi Bernabé-Pablo, Vojtech Jancik, Diego Martínez-Otero, Joaquín Barroso-Flores, and Mónica Moya-Cabrera* “Molecular Group 13 Metallaborates Derived from M−O−M Cleavage Promoted by BH3” Inorg. Chem. 2017, 56, 7890−7899

The second paper deals with heavier atoms and the bonds the formed around Yttrium complexes with triazoles, for which we calculated a more detailed distribution of the electronic density and concluded that the coordination of Cp to Y involves a high component of ionic character.

This paper is published in Ana Cristina García-Álvarez, Erandi Bernabé-Pablo, Joaquín Barroso-Flores, Vojtech Jancik, Diego Martínez-Otero, T. Jesús Morales-Juárez, Mónica Moya-Cabrera* “Multinuclear rare-earth metal complexes supported by chalcogen-based 1,2,3-triazole” Polyhedron 135 (2017) 10-16

We keep working on other projects and I hope we keep on doing so for the foreseeable future because those main group metals have been in my blood all this century. Thanks and a big shoutout to Dr. Monica Moya for keeping me in her highly productive and competitive team of researchers; here is to many more years of joint work.

All you wanted to know about Hybrid Orbitals…


… but were afraid to ask

or

How I learned to stop worrying and not caring that much about hybridization.

The math behind orbital hybridization is fairly simple as I’ll try to show below, but first let me give my praise once again to the formidable Linus Pauling, whose creation of this model built a bridge between quantum mechanics and chemistry; I often say Pauling was the first Quantum Chemist (Gilbert N. Lewis’ fans, please settle down). Hybrid orbitals are therefore a way to create a basis that better suits the geometry formed by the bonds around a given atom and not the result of a process in which atomic orbitals transform themselves for better sterical fitting, or like I’ve said before, the C atom in CH4 is sp3 hybridized because CH4 is tetrahedral and not the other way around. Jack Simmons put it better in his book:

2017-08-09 20.29.45

Taken from “Quantum Mechanics in Chemistry” by Jack Simmons

The atomic orbitals we all know and love are the set of solutions to the Schrödinger equation for the Hydrogen atom and more generally they are solutions to the hydrogen-like atoms for which the value of Z in the potential term of the Hamiltonian changes according to each element’s atomic number.

Since the Hamiltonian, and any other quantum mechanical operator for that matter, is a Hermitian operator, any given linear combination of wave functions that are solutions to it, will also be an acceptable solution. Therefore, since the 2s and 2p valence orbitals of Carbon do not point towards the edges of a tetrahedron they don’t offer a suitable basis for explaining the geometry of methane; even more so these atomic orbitals are not degenerate and there is no reason to assume all C-H bonds in methane aren’t equal. However we can come up with a linear combination of them that might and at the same time will be a solution to the Schrödinger equation of the hydrogen-like atom.

Ok, so we need four degenerate orbitals which we’ll name ζi and formulate them as linear combinations of the C atom valence orbitals:

ζ1a12s + b12px + c12py + d12pz

ζ2a22s + b22px + c22py + d22pz

ζ3a32s + b32px + c32py + d32pz

ζ4a42s + b42px + c42py + d42pz

to comply with equivalency lets set a1 = a2 = a3 = a4 and normalize them:

a12 + a22 + a32 + a42 = 1  ∴  ai = 1/√4

Lets take ζ1 to be directed along the z axis so b1 = c1 = 0

ζ= 1/√4(2s) + d12pz

since ζ1 must be normalized the sum of the squares of the coefficients is equal to 1:

1/4 + d12 = 1;

d1 = √3/2

Therefore the first hybrid orbital looks like:

ζ1 = 1/√4(2s) +√3/2(2pz)

We now set the second hybrid orbital on the xz plane, therefore c2 = 0

ζ2 = 1/√4(2s) + b22px + d22pz

since these hybrid orbitals must comply with all the conditions of atomic orbitals they should also be orthonormal:

ζ1|ζ2〉 = δ1,2 = 0

1/4 + d2√3/2 = 0

d2 = –1/2√3

our second hybrid orbital is almost complete, we are only missing the value of b2:

ζ2 = 1/√4(2s) +b22px +-1/2√3(2pz)

again we make use of the normalization condition:

1/4 + b22 + 1/12 = 1;  b2 = √2/√3

Finally, our second hybrid orbital takes the following form:

ζ2 = 1/√4(2s) +√2/√3(2px) –1/√12(2pz)

The procedure to obtain the remaining two hybrid orbitals is the same but I’d like to stop here and analyze the relative direction ζ1 and ζ2 take from each other. To that end, we take the angular part of the hydrogen-like atomic orbitals involved in the linear combinations we just found. Let us remember the canonical form of atomic orbitals and explicitly show the spherical harmonic functions to which the  2s, 2px, and 2pz atomic orbitals correspond:

ψ2s = (1/4π)½R(r)

ψ2px = (3/4π)½sinθcosφR(r)

ψ2pz = (3/4π)½cosθR(r)

we substitute these in ζ2 and factorize R(r) and 1/√(4π)

ζ2 = (R(r)/√(4π))[1/√4 + √2 sinθcosφ –√3/√12cosθ]

We differentiate ζ2 respect to θ, and set it to zero to find the maximum value of θ respect to the z axis we get the angle between the first to hybrid orbitals ζ1 and ζ2 (remember that ζ1 is projected entirely over the z axis)

dζ2/dθ = (R(r)/√(4π))[√2 cosθ –√3/√12sinθ] = 0

sinθ/cosθ = tanθ = -√8

θ = -70.53°,

but since θ is measured from the z axis towards the xy plane this result is equivalent to the complementary angle 180.0° – 70.53° = 109.47° which is exactly the angle between the C-H bonds in methane we all know! and we didn’t need to invoke the unpairing of electrons in full orbitals, their promotion of any electron into empty orbitals nor the ‘reorganization‘ of said orbitals into new ones. Orbital hybridization is nothing but a mathematical tool to find a set of orbitals which comply with the experimental observation and that is the important thing here!

To summarize, you can take any number of orbitals and build any linear combination you want, in order to comply with the observed geometry. Furthermore, no matter what hybridization scheme you follow, you still take the entire orbital, you cannot take half of it because they are basis functions. That is why you should never believe that any atom exhibits something like an sp2.5 hybridization just because their bond angles lie between 109 and 120°. Take a vector v = xi+yj+zk, even if you specify it to be v = 1/2i that means x = 1/2, not that you took half of the unit vector i, and it doesn’t mean you took nothing of j and k but rather than y = z = 0.

This was a very lengthy post so please let me know if you read it all the way through by commenting, liking, or sharing. Thanks for reading.

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