# Category Archives: Theoretical Chemistry

## Population Analysis in the Excited State with Gaussian

To calculate what the bonding properties of a molecule are in a particular excited state we can run any population analysis following the root of interest. This straightforward procedure takes two consecutive calculations since you don’t necessarily know before hand which excited state is the one of interest.

The regular Time Dependent Density Functional Theory (TD-DFT) calculation input with Gaussian 16 looks as follows (G09 works pretty much the same), let us assume we’ve already optimized the geometry of a given molecule:

%OldChk=filename.chk %nprocshared=16 %chk=filename_ES.chk #p TD(NStates=10,singlets) wb97xd/cc-pvtz geom=check guess=read Title Card Required 0 1 --blank line--

This input file retrieves the geometry and wavefunction from a previous calculation from filename.chk and doesn’t write anything new into it (that is what `%OldChk=filename.chk` means) and creates a new checkpoint where the excited states are calculated (`%chk=filename_ES.chk`)

In the output you search for the transition which peeks your interest; most often than not you’ll be interested in the one with the highest oscillator strength, *f*. The oscillator strength is a dimensionless number that represents the ratio of the observed, integrated, absorption coefficient to that calculated for a single electron in a three-dimensional harmonic potential [Harris & Bertolucci, Symmetry and Spectroscopy]; in other words, it is related to the probability of that transition to occur, and therefore it takes values from 0.0 to 1.0 (for single photon absorption processes.)

The output of this calculation looks as follows, the value of f for every excitation is reported together with its energy and the orbital transitions which comprise it.

Excitation energies and oscillator strengths: Excited State 1: Singlet-A 3.1085 eV 398.86 nm f=0.0043 <S**2>=0.000 56 -> 59 -0.11230 58 -> 59 0.69339 This state for optimization and/or second-order correction. Total Energy, E(TD-HF/TD-DFT) = -1187.56377917 Copying the excited state density for this state as the 1-particle RhoCI density. Excited State 2: Singlet-A 4.0827 eV 303.68 nm f=0.0016 <S**2>=0.000 52 -> 59 0.46689 52 -> 64 -0.20488 53 -> 59 0.19693 54 -> 59 0.40414 54 -> 64 -0.16261 ... ... Excited State 8: Singlet-A 5.2345 eV 236.86 nm f=0.8063 <S**2>=0.000 52 -> 60 0.17162 53 -> 59 0.47226 53 -> 60 -0.11771 54 -> 59 -0.27658 54 -> 60 -0.22006 55 -> 59 0.20496 56 -> 59 0.15029

Now we’ve selected excited state #8 because it has the largest value of f from the lot, we use the following input to read in the geometry from the old checkpoint file and we generate a new one in case we need it for something else. The input file for doing all this looks as follows (I’ve selected as usual the Natural Bond Orbital population analysis):

%oldchk=a_ES.chk %nprocshared=16 %chk=a_nbo.chk #p TD(Read,Root=8) wb97xd/cc-pvtz geom=check density=current guess=read pop=NBORead Title Card Required 0 1 $NBO BOAO BNDIDX E2PERT $END --blank line--

The flags at the bottom request the calculation of Wiberg Bond Indexes (BNDIDX) as well as Bond Order in the Atomic Orbital basis (BOAO) and a second order perturbation theory for the electronic delocalization (E2PERT). Now we can compare the population analysis between ground and the 8th excited state; check figure 1 and notice the differences in Wiberg’s bond order for this complex made of two molecules and one Na+ cation.

In this example we can observe that in the ground state we have a neutral and a negative molecule together with a Na+ cation, but when we analyze the population in the 8th excited state both molecules acquire a similar charge, ca. **0.46 e**, which means that some of the electron density has been transferred from the negative one to the neutral molecule, forming an

*Electron Donor-Acceptor*complex (EDA) in the excited state.

This procedure can be extended to any other kind of population analysis and their derived combination, e.g. one could calculate their condensed fukui functions in the Nth excited state; but beware! These calculations yield vertical excitations, should the excited state of interest have a minimum we can first optimize the ES geometry and then perform the population analysis on said geometry; just add the opt keyword to perform both jobs in one go, but bear in mind that the NBO population analysis is performed before and after the optimization process so look for the tables and values closer to the end of the output file.

In the case of open shell systems the procedure is the same but one should be extremely careful in searching for the total population analysis since the output file contains this table for the alpha and beta populations separately as well as the added values for the total number of electrons.

## Percentage of Molecular Orbital Composition – G09,G16

Canonical Molecular Orbitals are–by construction–delocalized over the various atoms making up a molecule. In some contexts it is important to know how much of any given orbital is made up by a particular atom or group of atoms, and while you could calculate it by hand given the coefficients of each MO in terms of every AO (or basis set function) centered on each atom there is a straightforward way to do it in Gaussian.

If we’re talking about ‘dividing’ a molecular orbital into atomic components, we’re most definitely talking about population analysis calculations, so we’ll resort to the ** pop** keyword and the

**option in the standard syntax:**

`orbitals`#p M052x/cc-pVDZ pop=orbitals

This will produce the following output right after the Mulliken population analysis section:

Atomic contributions to Alpha molecular orbitals: Alpha occ 140 OE=-0.314 is Pt1-d=0.23 C38-p=0.16 C31-p=0.16 C36-p=0.16 C33-p=0.15 Alpha occ 141 OE=-0.313 is Pt1-d=0.41 Alpha occ 142 OE=-0.308 is Cl2-p=0.25 Alpha occ 143 OE=-0.302 is Cl2-p=0.72 Pt1-d=0.18 Alpha occ 144 OE=-0.299 is Cl2-p=0.11 Alpha occ 145 OE=-0.298 is C65-p=0.11 C58-p=0.11 C35-p=0.11 C30-p=0.11 Alpha occ 146 OE=-0.293 is C58-p=0.10 Alpha occ 147 OE=-0.291 is C22-p=0.09 Alpha occ 148 OE=-0.273 is Pt1-d=0.18 C11-p=0.12 C7-p=0.11 Alpha occ 149 OE=-0.273 is Pt1-d=0.18 Alpha vir 150 OE=-0.042 is C9-p=0.18 C13-p=0.18 Alpha vir 151 OE=-0.028 is C7-p=0.25 C16-p=0.11 C44-p=0.11 Alpha vir 152 OE=0.017 is Pt1-p=0.10 Alpha vir 153 OE=0.021 is C36-p=0.15 C31-p=0.14 C63-p=0.12 C59-p=0.12 C38-p=0.11 C33-p=0.11 Alpha vir 154 OE=0.023 is C36-p=0.13 C31-p=0.13 C63-p=0.11 C59-p=0.11 Alpha vir 155 OE=0.027 is C65-p=0.11 C58-p=0.10 Alpha vir 156 OE=0.029 is C35-p=0.14 C30-p=0.14 C65-p=0.12 C58-p=0.11 Alpha vir 157 OE=0.032 is C52-p=0.09 Alpha vir 158 OE=0.040 is C50-p=0.14 C22-p=0.13 C45-p=0.12 C17-p=0.11 Alpha vir 159 OE=0.044 is C20-p=0.15 C48-p=0.14 C26-p=0.12 C54-p=0.11

Alpha and Beta densities are listed separately only in unrestricted calculations, otherwise only the first is printed. Each orbital is listed sequentially (occ = occupied; vir = virtual) with their energy value (OE = orbital energy) in atomic units following and then the fraction with which each atom contributes to each MO.

By default only the ten highest occupied orbitals and ten lowest virtual orbitals will be assessed, but the number of MOs to be analyzed can be modified with ** orbitals=N**, if you want to have all orbitals analyzed then use the option

**instead of just**

`AllOrbitals``. Also, the threshold used for printing the composition is set to 10% but it can be modified with the option`

**orbitals**`, for the same compound as before here’s the output lines for HOMO and LUMO (MOs 149, 150) with ThreshOrbitals set to N=1, i.e. 1% as occupation threshold (`

**ThreshOrbitals=N**`):`

**ThreshOrbitals=1**Alpha occ 149 OE=-0.273 is Pt1-d=0.18 N4-p=0.08 N6-p=0.08 C20-p=0.06 C13-p=0.06 C48-p=0.06 C9-p=0.06 C24-p=0.05 C52-p=0.05 C16-p=0.04 C44-p=0.04 C8-p=0.03 C15-p=0.03 C17-p=0.03 C45-p=0.02 C46-p=0.02 C18-p=0.02 C26-p=0.02 C54-p=0.02 N5-p=0.01 N3-p=0.01 Alpha vir 150 OE=-0.042 is C9-p=0.18 C13-p=0.18 C44-p=0.08 C16-p=0.08 C15-p=0.06 C8-p=0.06 N6-p=0.04 N4-p=0.04 C52-p=0.04 C24-p=0.04 N5-p=0.03 N3-p=0.03 C46-p=0.03 C18-p=0.03 C48-p=0.02 C20-p=0.02

The ` fragment=n` label in the coordinates can be used as in BSSE Counterpoise calculations and the output will show the orbital composition by fragments with the label

`"Fr"`, grouping all contributions to the MO by the AOs centered on the atoms in that fragment.

As always, thanks for reading, sharing, and rating. I hope someone finds this useful.

## DFT beyond academia

Density Functional Theory is by far the most successful way of gaining access to molecular properties starting from their composition. Calculating the electronic structure of molecules or solid phases has become a widespread activity in computational as well as in experimental labs not only for shedding light on the properties of a system under study but also as a tool to design those systems with taylor-made properties. This level of understanding of matter brought by DFT is based in a rigorous physical and mathematical development, still–and maybe because of it–DFT (and electronic structure calculations in general for that matter) might be thought of as something of little use outside academia.

Prof. Juan Carlos Sancho-García from the University of Alicante in Spain, encouraged me to talk to his students last month about the reaches of DFT in the industrial world. Having once worked in the IP myself I remembered the simulations performed there were mostly DPD (Dissipative Particle Dynamics), a coarse grained kind of molecular dynamics, for investigating the interactions between polymers and surfaces, but no DFT calculations were ever on sight. It is widely known that Docking, QSAR, and Molecular Dynamics are widely used in the pharma industry for the development of new drugs but I wasn’t sure where DFT could fit in all this. I thought patent search would be a good descriptor for the commercial applicability of DFT. So I took a shallow dive and searched for patents explicitly mentioning the use of DFT as part of the invention development process and protection. The first thing I noticed is that although they appear to be only a few, these are growing in numbers throughout the years (Figure 1). Again, this was not an exhaustive search so I’m obviously overlooking many.

The second thing that caught my attention was that the first hit came from 1998, nicely coinciding with the rise of B3LYP (Figure 2). This patent was awarded to Australian inventors from the University of Wollongong, South New Wales to determine trace gas concentrations by chromatography by means of calculating the FT-IR spectra of sample molecules (Figure 3), so DFT is used as part of the invention but I ignore if this is a widespread method in analytical labs.

While I’m mentioning the infamous B3LYP functional, a search about it in patents yields the following graph (Figure 4), most of which relate to the protection of photoluminescent or thermoluminescent molecules for light emitting devices; it appears that DFT calculations are used to provide the key features of their protection, such as HOMO-LUMO gap etc.

**Figure 4**– Patents bearing B3LYP as part of their invention

So what about software? Most of the more recent patents in Figure 1 (2018 – 2022) lie in the realm of electronics, particularly the development of semiconductors, ceramical or otherwise, so it was safe to assume VASP could be a popular choice to that end, right? turns out that’s not necessarily the case since a patent search for VASP only accounts for about the 10% of all awarded patents (Figure 5).

I guess it’s safe to say by now that DFT has a significant impact in the industrial development, one could only expect it to keep on rising, however the advent of machine learning techniques and other artificial intelligence related methods promise an accelerated development. I went again to the patents database and this time searched for ‘*machine learning *development *materials*‘ (the term ‘development’ was deleted by the search engine, guess found it too obvious) and its rise is quite notorious, surpassing the frequency of DFT in patents (Figure 6), particularly in the past 5 years (2018 – 2022).

**Figure 6**– The rise of the machines in materials development

I’m guessing in some instances DFT and ML will tend to go hand in hand in the industrial development process, but the timescales reachable by ML will only tend to grow, so I’m left with the question of what are we waiting for to make ML and AI part of the chemistry curricula? As computational chemistry teachers we should start talking about this points with our students and convince the head of departments to help us create proper courses or we risk our graduates to become niche scientists in a time when new skills are sought after in the IP.

__________________________________________________________________________________

Thanks again to Prof. Juan Carlos Sancho García at the University of Alicante, Spain, who asked me talk about the subject in front of his class, and to Prof. José Pedro Cerón-Carrasco from Cartagena for allowing me to talk about this and other topics at Centro Universitario de la Defensa. Thank you, guys! I look forward to meeting you again soon.

## Worldwide CompChem in the Fight against COVID-19

The war against COVID-19 has been waged in many fronts. The computational chemistry community has done their share during this pandemic to put forward a cure, a vaccine, or a better understanding of the molecular mechanisms behind the human infection by the SARS-CoV-2 virus. As few vaccines show currently their heads and start making their way around the globe to stop the spreading, amidst a climate of disinformation, distrust and political upheaval, all of which pose several challenges yet to be faced aside from the technical and scientific ones.

This is by no means a comprehensive review of the literature, in fact, most of the cited literature herein was observed in Twitter under the #CompChem and #COVID combined hashtags; Summarizing the research by the CompChem community on COVID-19 related topics in a single blog-post would be near to impossible—I trust a book is being written on it as I type these lines.

The structural elucidation of the proteins associated to the SARS-CoV-2 virus is probably the first step required in designing chemical compounds capable of modifying their functions and altering their life-cycle without altering the biochemistry of the hosts. The Coronavirus Structural Taskforce has elucidated the structure of 28 proteins of SARS-CoV-2 aside from the 300+ proteins from the previous SARS-CoV virus using the tools from the FoldIt at home game based on the Rosetta program to heuristically predict the structure of these proteins. Structure based drug design rely on the knowledge of the structure of the active site (hence the name), but in the case of newly discovered proteins for which homology modeling is not entirely feasible, a ligand-based approach named D3Similarity was developed early in the pandemic for identifying the possible active sites by the group of Prof. Zhijian Xu. Mapping of the of the viral genome and proteome was also achieved early on during the first dates of lockdown in the American continent. The information was readily made available and usable for further studies which prompts another challenge: the rapid dissemination, review and evaluation of information to make scientifically sound claims and make data-based decisions. In this regard, the role of preprints cannot be stressed enough. Without a rapid communication, scientific results cannot generate a much needed critical mass to turn all these data into knowledge. As evidenced by the vast majority of the links present in this post, ChemRXiv from the ACS served the much needed function to gather, link and put the data for scientific evaluation out there in order to accelerate the discovery of solutions to the various steps of the virus’ reproductive cycle through various strategies.

The role of supercomputing has been paramount worldwide to the various efforts made in CompChem (read the C&EN piece) in various fronts from structural elucidation, such as the AI driven structural modelling of spike proteins and their infection mechanism led by Prof. Rommie Amaro (UCSD) and Dr. Arvind Ramanathan which was celebrated by the Bell Prize, to development of vaccines. Many Molecular Dynamics simulations have been performed on potential inhibitors of proteins such as the spike protein, in some cases these simulations coupled with cryo-EM microscopy allowed for the elucidation of the hinging mechanism of these spike proteins, their thermodynamic properties, and all atoms-simulations assessed the rigidity of the receptor as the cause of its infectivity. Still, owning these computing resources isn’t always cost effective; that’s why there have been outsourced to companies such as Amazon web services as Pearlman did for the QM/DFT calculations of the binding energy of several drug candidates for the inhibition of the virus’ main protease (MPro). Many other CADD studies are available (here, here, and here). Researchers from all around the world can chip in and join the effort by reaching out to the COVID-19 High Performance Computing Consortium (HPC) which brings together some of the most advanced computing systems to the hands of private and academic researchers with relevant projects aimed to the study of the virus. On the other side of the Atlantic, the Partnership for Advanced Computing in Europe (PRACE) also provides access to advanced computing services for research. As an effort to keep all the developing information curated and concentrated, the COVID-19 Molecular Structure and Therapeutics Hub was created to provide a community-driven data repository and curation service for molecular structures, models, therapeutics, and simulations related to computational research related to therapeutic opportunities.

As described above, molecular dynamics simulations are capital in the assessment of how drugs interact with proteins. But molecular dynamics can only do so much as they’re computing intensive so, the use of Polarizable Force Fields (PFF) algorithms to obtain results in the microseconds regime with high-resolution sampling methods which have been applied also to the modeling of the MPro protein; the phase space is sampled by different MD trajectories which are then tested and selected. Aside from classical simulations, artificial intelligence predictions and docking calculations, also quantum mechanical calculations have been employed in the search for the most intimate interactions governing the mechanisms of inhibition of proteins. In this front, a Fragment Molecular Orbital based analysis was carried out to find which residues in MPro interacted the most with a given inhibitor.

Virtual screening is at the heart of the computationally aided drug discovery process, specially high-throughput virtual screening such as the one performed by the group of Andre Fischer at Basel, in which 11 potential drugs were narrowed from a pool of over 600 million compounds that were analyzed as potential protease inhibitors. Repurposing of antiviral drugs, and other entry-inhibiting compounds, is also a major avenue explored in the search for treatments; in the linked study by Shailly Tomar et al. antiviral drugs which are also anti inflammatory are believed to take care of lung inflammation and injury associated to the infection at the same time they tend to disrupt the virus’ infection mechanism. The comeback of Virtual Reality can make virtual screening more cooperative even during lockdown conditions and more ‘tangible’ as the company Nanome has proven with their COVID-19 Town Hall meetings which aim to the modeling of proteins in 3D space. Aside from the de novo and repurposing efforts, the search for peptides against infection by SARS-CoV-2 was an important topic (here and here). More recently, Skariyachan and Gopal turn to natural products from herbal origins for their virtual screening (molecular docking and dynamics). In their perspective the chemical complexity achieved through biosynthesis can overcome the bottleneck of chemical discovery while at the same time turning to the ancient practices of herbal remedies described in Ayurveda. Other researchers like Manish Manish have also turned to libraries of 500,000+ natural compounds to find potential drugs for MPro.

The year is coming to an end but not the pandemic in any way. Now, with the advent of new strains, and the widespread vaccination effort put in place, it is more important than ever to keep the fight strong in our labs but also in our personal habits and responsibilities—the same advices that were given at the beginning of the year are still in effect today and will continue to be for the months to come. I want to wish everyone who reads this a happy holiday season, but above all I want to pay a small tribute to the scientists working relentlessly in one of the largest coordinated scientific efforts in modern history, one that can only be compared to the Moon landing or the Manhattan Project; to those scientists and all the healthcare personnel, may you find rest soon, may your efforts never go unnoticed: Thank you for your service.

## Basis Set Superposition Error (BSSE). A short intro

Molecular Orbitals (MOs) are linear combinations of Atomic Orbitals (AOs), which in turn are linear combinations of other functions called ‘basis functions’. A basis, or more accurately a basis set, is a collection of functions which obey a set of rules (such as being orthogonal to each other and possibly being normalized) with which all AOs are constructed, and although these are centered on each atomic nucleus, the canonical way in which they are combined yield delocalized MOs; in other words, an MO can occupy a large space spanning several atoms at once. We don’t mind this expansion across a molecule, but what about between two molecules? Calculating the interaction energy between two or more molecular fragments leads to an artificial extra–stabilization term that stems from the fact that electrons in molecule 1 can occupy AO’s (or the basis functions which form them) centered on atoms from molecule 2.

Fundamentally, the interaction energy of any A—B dimer, *E _{int}*, is calculated as the energy difference between the dimer and the separately calculated energies for each component (Equation 1).

*E _{int} = E_{AB} – E_{A} – E_{B}* (

**1**)

However the calculation of *E _{int} *by this method is highly sensitive to the choice of basis set due to the Basis Set Superposition Error (BSSE) described in the first paragraph. The BSSE is particularly troublesome when small basis sets are used, due to the poor description of dispersion interactions but treating this error by just choosing a larger basis set is seldom useful for systems of considerable sizes. The Counterpoise method is a nifty correction to equation 1, in which EA and EB are calculated with the basis set of A and B respectively, i.e., only in EAB a larger basis set (that of A and B simultaneously) is used. The Counterpoise method calculates each component with the AB basis set (Equation 2)

*E _{int}^{CP} = E_{AB}^{AB} – E_{A}^{AB}– E_{B}^{AB}* (

**2**)

where the superscript AB means the whole basis set is used. This is accomplished by using ‘*ghost*‘ atoms with no nuclei and no electrons but empty basis set functions centered on them.

In Gaussian, BSSE is calculated with the Counterpoise method developed by Boys and Simon. It requires the keyword Counterpoise=N where N is the number of fragments to be considered (for an A—B system, N=2). Each atom in the coordinates list must be specified to which fragment pertains; additionally, the charge and multiplicity for each fragment and the whole supermolecular ensemble must be specified. Follow the example of this hydrogen fluoride dimer.

%chk=HF2.chk #P opt wB97XD/6-31G(d,p) Counterpoise=2 HF dimer 0,1 0,1 0,1 H(Fragment=1) 0.00 0.00 0.00 F(Fragment=1) 0.00 0.00 0.70 H(Fragment=2) 0.00 0.00 1.00 F(Fragment=2) 0.00 0.00 1.70

For closed shell fragments the first line is straightforward but one must pay attention that the first pair of numbers in the charge multiplicity line correspond to the whole ensemble, whereas the folowing pairs correspond to each fragment in consecutive order. Fragments do not need to be specified contiguously, i.e., you don’t need to define all atoms for fragment 1 and after those the atoms for fragment 2, etc. They could be mixed and the program still assigns them correctly. Just as an example I typed wB97XD but any other method, DFT or ab initio, may be used; only semiempirical methods do not admit a BSSE calculation because they don’t make use of a basis set in the first place!

The output provides the corrected energy (in atomic units) for the whole system, as well as the BSSE correction (which added to the previous term yields the un-corrected energy of the system). Gaussian16 also provides these values in kcal/mol as ‘Complexation energies’ first raw (uncorrected) and then the corrected energy.

BSSE is always present and cannot be entirely eliminated because of the use of finite basis sets but it can be correctly dealt with if the Counterpoise method is included.

## Density Keyword in Excited State Calculations with Gaussian

I have written about extracting information from excited state calculations but an important consideration when analyzing the results is the proper use of the keyword *density*.

This keyword let’s Gaussian know which density is to be used in calculating some results. An important property to be calculated when dealing with excited states is the change in dipole moment between the ground state and any given state. The Transition Dipole Moment is an important quantity that allows us to predict whether any given electronic transition will be allowed or not. A change in the dipole moment (i.e. non-zero) of a molecule during an electronic transition helps us characterize said transition.

Say you perform a TD-DFT calculation without the *density* keyword, the default will provide results on the lowest excited state from all the requested states, which may or may not be the state of interest to the transition of interest; you may be interested in the dipole moment of all your excited states.

Three separate calculations would be required to calculate the change of dipole moment upon an electronic transition:

1) A regular DFT for the ground state as a reference

2) TD-DFT, to calculate the electronic transitions; request as many states as you need/want, analyze it and from there you can see which transition is the most important.

3) Request the density of the Nth state of interest to be recovered from the checkpoint file with the following route section:

# TD(Read,Root=N)LOTDensity=Current Guess=Read Geom=AllCheck

replace *N* for the *N*th state which caught your eye in step number 2) and *LOT* for the *Level of Theory* you’ve been using in the previous steps. That should give you the dipole moment for the structure of the *N*th excited state and you can compare it with the one in the ground state calculated in 1). Again, if density=current is not used, only properties of *N*=1 will be printed.

## Orbital Contributions to Excited States

This is a guest post by our very own Gustavo “*Gus*” Mondragón whose work centers around the study of excited states chemistry of photosynthetic pigments.

When you’re calculating excited states (no matter the method you’re using, TD-DFT, CI-S(D), EOM-CCS(D)) the analysis of the orbital contributions to electronic transitions poses a challenge. In this post, I’m gonna guide you through the CI-singles excited states calculation and the analysis of the electronic transitions.

I’ll use adenine molecule for this post. After doing the corresponding geometry optimization by the method of your choice, you can do the excited states calculation. For this, I’ll use two methods: CI-Singles and TD-DFT.

The route section for the CI-Singles calculation looks as follows:

%chk=adenine.chk

%nprocshared=8

%mem=1Gb

#p CIS(NStates=10,singlets)/6-31G(d,p) geom=check guess=read scrf=(cpcm,solvent=water)

adenine excited states with CI-Singles method

0 1

--blank line--

I use the same geometry from the optimization step, and I request only for 10 singlet excited states. The CPCP implicit solvation model (solvent=water) is requested. If you want to do TD-DFT, the route section should look as follows:

%chk=adenine.chk

%nprocshared=8

%mem=1Gb

#p FUNCTIONAL/6-31G(d,p) TD(NStates=10,singlets) geom=check guess=read scrf=(cpcm,solvent=water)

adenine excited states with CI-Singles method

0 1

--blank line--

Where FUNCTIONAL is the DFT exchange-correlation functional of your choice. Here I strictly not recommend using B3LYP, but CAM-B3LYP is a noble choice to start.

Both calculations give to us the excited states information: excitation energy, oscillator strength (as *f* value), excitation wavelength and multiplicity:

Excitation energies and oscillator strengths:

Excited State 1: Singlet-A 6.3258 eV 196.00 nm f=0.4830 <S**2>=0.000

11 -> 39 -0.00130

11 -> 42 -0.00129

11 -> 43 0.00104

11 -> 44 -0.00256

11 -> 48 0.00129

11 -> 49 0.00307

11 -> 52 -0.00181

11 -> 53 0.00100

11 -> 57 -0.00167

11 -> 59 0.00152

11 -> 65 0.00177

The data below corresponds to all the electron transitions involved in this excited state. I have to cut all the electron transitions because there are a lot of them for all excited states. If you have done excited states calculations before, you realize that the HOMO-LUMO transition is always an important one, but not the only one to be considered. Here is when we calculate the *Natural Transition Orbitals *(NTO), by these orbitals we can analyze the electron transitions.

For the example, I’ll show you first the HOMO-LUMO transition in the first excited state of adenine. It appears in the long list as follows:

35 -> 36 0.65024

The 0.65024 value corresponds to the transition amplitude, but it doesn’t mean anything for excited state analysis. We must calculate the NTOs of an excited state from a new Gaussian input file, requesting from the checkpoint file we used to calculate excited states. The file looks as follows:

%Oldchk=adenine.chk

%chk=adNTO1.chk

%nproc=8

%mem=1Gb

#p SP geom=allcheck guess=(read,only) density=(Check,Transition=1) pop=(minimal,NTO,SaveNTO)

I want to say some important things right here for this last file. See that no level of theory is needed, all the calculation data is requested from the checkpoint file “adenine.chk”, and saved into the new checkpoint file “adNTO1.chk”, we must use the previous calculated density and specify the transition of interest, it means the excited state we want to analyze. As we don’t need to specify charge, multiplicity or even the comment line, this file finishes really fast.

After doing this last calculation, we use the new checkpoint file “adNTO1.chk” and we format it:

formchk -3 adNTO1.chk adNTO1.fchk

If we open this formatted checkpoint file with GaussView, chemcraft or the visualizer you want, we will see something interesting by watching he MOs diagram, as follows:

We can realize that frontier orbitals shows the same value of 0.88135, which means the real transition contribution to the first excited state. As these orbitals are contributing the most, we can plot them by using the cubegen routine:

cubegen 0 mo=homo adNTO1.fchk adHOMO.cub 0 h

This last command line is for plotting the equivalent as the HOMO orbital. If we want to plot he LUMO, just change the “homo” keyword for “lumo”, it doesn’t matter if it is written with capital letters or not.

You must realize that the Natural Transition Orbitals are quite different from Molecular Orbitals. For visual comparisson, I’ve printed also the molecular orbitals, given from the optimization and from excited states calculations, without calculating NTOs:

These are the molecular frontier orbitals, plotted with Chimera with 0.02 as the isovalue for both phase spaces:

The frontier NTOs look qualitatively the same, but that’s not necessarily always the case:

If we analyze these NTOs on a hole-electron model, the HOMO refers to the *hole* space and the LUMO refers to the *electron* space.

Maybe both orbitals look the same, but both frontier orbitals are quite different between them, and these last orbitals are the ones implied on first excited state of adenine. The electron transition will be reported as follows:

If I can do a graphic summary for this topic, it will be the next one:

NTOs analysis is useful no matter if you calculate excited states by using CIS(D), EOM-CCS(D), TD-DFT, CASSCF, or any of the excited states method of your election. These NTOs are useful for population analysis in excited states, but these calculations require another software, MultiWFN is an open-source code that allows you to do this analysis, and another one is called TheoDORE, which we’ll cover in a later post.

## NIST CCCBDB – Vibrational Scaling Factors & ThermoChem Data

The Computational Chemistry Comparison and Benchmark DataBase (CCCBDB) from the National Institute of Standards and Technology (NIST) collects experimental and calculated thermochemistry—related values for 1968 common molecules, constituting a vast source of benchmarks for various kinds of calculations.

In particular, scaling factors for vibrational frequencies are very useful when calculating vibrational spectra. These scaling factors are arranged by levels of theory ranging from HF to MP2, DFT, and multireference methods. These scaling factors are obtained by least squares regression between experimental and calculated frequencies for a set of molecules at a given level of theory.

Aside from vibrational spectroscopy, a large number of structural and energetic properties can be found and estimated for small molecules. A quick formation enthalpy can be calculated from experimental data and then compared to the reported theoretical values at a large number of levels of theory. Moments of inertia, enthalpies, entropies, charges, frontier orbital gaps, and even some odd values or even calculations gone awry are pointed out for you to know if you’re dealing with a particularly problematic system. The CCCB Database includes tutorials and input/output files for performing these kinds of calculations around thermochemistry, making it also a valuable learning resource.

Every computational chemist should be aware of this site, particularly when collaborating with experimentalists or when carrying calculations trying to replicate experimental data. The vastness of the site calls for a long dive to explore their possibilities and capabilities for more accurate calculations.

## XVIII RMFQT

It was my distinct pleasure for me to participate in the organization of the latest edition of the Mexican Meeting on Theoretical Physical Chemistry, RMFQT which took place last week here in Toluca. With the help of the School of Chemistry from the Universidad Autónoma del Estado de México.

This year the national committee created a Lifetime Achievement Award for Dr. Annik Vivier, Dr. Carlos Bunge, and Dr. José Luis Gázquez. This recognition from our community is awarded to these fine scientists for their contributions to theoretical chemistry but also for their pioneering work in the field in Mexico. The three of them were invited to talk about any topic of their choosing, particularly, Dr. Vivier stirred the imagination of younger students by showing her pictures of the times when she used to hangout with Slater, Roothan, Löwdin, etc., it is always nice to put faces onto equations.

Continuing with a recent tradition we also had the pleasure to host three invited plenary lectures by great scientists and good friends of our community: Prof. William Tiznado (Chile), Prof. Samuel B. Trickey (USA), and Prof. Julia Contreras (France) who shared their progress on their recent work.

As I’ve abundantly pointed out in the past, the RMFQT is a joyous occasion for the Mexican theoretical community to get together with old friends and discuss very exciting research being done in our country and by our colleagues abroad. I’d like to add a big shoutout to Dr. Jacinto Sandoval-Lira for his valuable help with the organization of our event.

## Useful Thermochemistry from Gaussian Calculations

Statistical Mechanics is the bridge between microscopic calculations and thermodynamics of a particle ensemble. By means of calculating a partition function divided in electronic, rotational, translational and vibrational functions, one can calculate all thermodynamic functions required to fully characterize a chemical reaction. From these functions, the vibrational contribution, together with the electronic contribution, is the key element to getting thermodynamic functions.

Calculating the Free Energy change of any given reaction is a useful approach to asses their thermodynamic feasibility. A large negative change in Free Energy when going from reagents to products makes up for a quantitative spontaneous (and exothermic) reaction, nevertheless the rate of the reaction is a different story, one that can be calculated as well.

Using the **freq** option in your route section for a Gaussian calculation is mandatory to ascertain the current wave function corresponds to a minimum on a potential energy hypersurface, but also yields the thermochemistry and thermodynamic values for the current structure. However, thermochemistry calculations are not restricted to minima but it can also be applied to transition states, therefore yielding a full thermodynamic characterization of a reaction mechanism.

A regular **freq** calculation yields the following output (all values in atomic units):

Zero-point correction= 0.176113 (Hartree/Particle) Thermal correction to Energy= 0.193290 Thermal correction to Enthalpy= 0.194235 Thermal correction to Gibbs Free Energy= 0.125894 Sum of electronic and zero-point Energies= -750.901777 Sum of electronic and thermal Energies= -750.884600 Sum of electronic and thermal Enthalpies= -750.883656Sum of electronic and thermal Free Energies= -750.951996

For any given reaction say A+B -> C one could take the values from the last row (lets call it G) for all three components of the reaction and perform the arithmetic: DG = GC – [GA + GB], so products minus reagents.

By default, Gaussian calculates these values (from the previously mentioned partition function) using normal conditions, T = 298.15 K and P = 1 atm. For an assessment of the thermochemistry at other conditions you can include in your route section the corresponding keywords **Temperature=**x.x and **Pressure=**x.x, in Kelvin and atmospheres, respectively.

(Huge) **Disclaimer**: Although calculating the thermochemistry of any reaction by means of DFT calculations is a good (and potentially very useful) guide to chemical reactivity, getting quantitative results require of high accuracy methods like G3 or G4 methods, collectively known as Gn mehtods, which are composed of pre-defined stepwise calculations. The sequence of these calculations is carried out automatically; no basis set should be specified. Other high accuracy methods like CBS-QB3 or W1U can also be considered whenever Gn methods are too costly.