Its well known fact, potential energy generated by molecular minimization usually used to check molecules stability and is the function of torsion energy, bend energy, bond stretch energy, electrostatics energy, solvation energy, van der Waals energy and others internal energy.
But can we compare the stability of different molecules on the basis of potential energy values we get by using some force field based minimization?
No. The energies of different molecules calculated using MM will be different, because they will have different number and kind of bonds, angles, torsional angles and interactions. Such values will bear no information about their stability and it makes no sense to compare enegy values of different molecules.
You can compare the energies of e.g. two isomers: if they have identical atoms and bonds the energy comparison will be relevant. But that still does not tell much about their stability, since in MM all molecules are by definition stable (since there is no bond breaking).
No. The energies of different molecules calculated using MM will be different, because they will have different number and kind of bonds, angles, torsional angles and interactions. Such values will bear no information about their stability and it makes no sense to compare enegy values of different molecules.
You can compare the energies of e.g. two isomers: if they have identical atoms and bonds the energy comparison will be relevant. But that still does not tell much about their stability, since in MM all molecules are by definition stable (since there is no bond breaking).
Perhaps you should look for heat of formation of each molecule. That can give you a rough idea of stability. However, you do not define stability in what?
Molecules can go through, oxidation, reduction, photolysis, hydrolysis and bacterial attack, as soon as they get synthesized. First define to what type of stability are looking at and then perhaps we could help you.
As a rule of thumb, energies obtained via molecular mechanism methods tend to be rough and inaccurate, that is where AB initio or semi-empirical methods can have a preponderant role in your research.
Mr Martin,
We are designing molecules by isosteric replacement of certain part, so that the biological and chemical reactivity of the resulted molecule should't be disturbed a lot.
So, my objective is to check, does the isosteric replacement disturbs the structural stability of a molecule, that's why I thought force field based molecular minimization, which is used thoroughly to minimize the structures can give me some potential information.
This far I get to know, the PE value can be good for isomers, but what about the case for isosteric compounds, how to measure and compare their stability or if not comparing, can we scale the PE obtained after minimization from different structure and say the molecule having least PE is more good or structurally more stable for isosteric compounds.
Please help. I will appreciate any potential guidance.
Ab initio quantum chemical methods or, at least, density functional theory would work much better for your purposes.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there must be estudies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on add non-reactive functional groups to your analogs.
PE gives you an idea of the molecular strain, for example, molecular substituents with increase molecular or steric hindrance will theoretically have a higher PE energy. IF the functional group rearranges it can be lower however...
Now, there are studies doing AB initio calculations on a series of analogs suggesting which analog is easier to make. In other words, which synthetic pathway is more prone to be followed for the substrate in its way to get converted into a product. So, this is the synthetic chem answer.
But, if you have reactive functional groups I would suggest to go to a PKD book and check what substituents are more prone to go through oxidation, hydrolysis, etc. This is the PK answer.
The practical answer would be this:
Forget about energies unless the minimized molecule has a really high one and focus on adding non-reactive functional groups to your analogs.
Thanks Mr Martin
Its really an interesting answer, I have already cross-checked the molecules for the reactive functional groups and have removed them.
And as per your answer and the literature analysis, we can say that PE is a quantitative term, which actually explains the quality of any molecular structure, then I am just curious, why we can't use it as descriptor to quantify and compare the stability of different isosteric molecules?
Hope my curiosity is not baseless and I am not wasting the important time of you guys.
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