Rotatable bond identification issue

Hi,


I'm using the Topology Analyser Plugin to identify rotating bonds.


Some rotating bonds, on certain molecules, are not identified as rotating.





I've attached three examples that I've found: the rotating bonds are highlighted in green, but there are others (the ones between the cycles) that are not identified as rotating.


I've also attached a Java program to generate that image.


Is there any workaround to this?





Thank you!


Simone

Hi Simone,





Thank you for the good comment! Currently, Topology Analyser considers the following bonds as NON-rotating ones:





- non-single bonds


- bonds to hydrogens


- bonds to terminal atoms (CH3, NH2, etc)


- ring bonds


- bonds of amides, thioamides, suplphonamides


- bonds connecting aromatic rings having 3 ortho substituents





- bonds connected to the terminal triple bonds (like cyano) is already implemented for the next release version 5.1, it has not been released yet





What other rules do you propose?





Gyuri

Gyuri wrote:

Thank you for the good comment! Currently, Topology Analyser considers the following bonds as NON-rotating ones: - non-single bonds - bonds to hydrogens - bonds to terminal atoms (CH3, NH2, etc) - ring bonds - bonds of amides, thioamides, suplphonamides - bonds connecting aromatic rings having 3 ortho substituents - bonds connected to the terminal triple bonds (like cyano) is already implemented for the next release version 5.1, it has not been released yet

Thanks for the listing.

Gyuri wrote:

What other rules do you propose?

The bonds connected to an ethyne group are not rotatable, too (as the bond after a cyano group).


So in

Code:

CCC#CCC

there is one large rotatable bond in the middle, resulting in total ONE rotatable bond.


cxcalc spits out 2 for this molecule...





lorenz

In case of terminal triple bonds like cyano, I can rotate the connected single bond, but due to the linear ligand, the rotation does not change the core conformation (hydrogens are ignored). So it is not considered rotatable.





CCC#CCC has no terminal triple bond, so the rotating two connected single bonds (highlighted in the attached screenshot with red) will modify the core conformation.

Gyuri wrote:

CCC#CCC has two rotatable bonds, highlighted in the attached screenshot with red.

Well, if I look at it, these bonds are not really rotatable at the C#C end. You can rotate the triple bond as you want, the molecule stays symetrically and chemically the same. So I suggest to consider the whole as one long stick with rotatable methy arms...?

I don't think, that symmetry would be important when we count the number of rotatable bonds. If the rotation of a bond is not prohibited and can change the conformation of the molecule, we need to count it. According to your approach, 1,4-diethylbenzene would have 1 rotatable bond only? What about symmetrically para-substituted biphenyls?





Anyway, PubChem says, that 3-hexyne has no rotatable bonds. Nothing is perfect. :-)

Gyuri wrote:

Anyway, PubChem says, that 3-hexyne has no rotatable bonds. Nothing is perfect. :-)

Ok, that's even worse :)

Gyuri wrote:

I don't think, that symmetry would be important when we count the number of rotatable bonds. If the rotation of a bond is not prohibited and can change the conformation of the molecule, we need to count it.

Well I think we run straightforward into a definition of rotatable bonds. (Is there any official definition?) For me a rotatable bond is not only a bond, its rather a "unit" which allows rotation of attached groups.


Or to do metaphorically speaking:


If I grab the middle bond of propane and shake it then the two methyl groups wobble around. So this is a rotatable bond.


If I grab the middle of 3-hexyne then only the two methyl groups will move, so the whole 2-butyne unit is one "rotatable bond".

Gyuri wrote:

According to your approach, 1,4-diethylbenzene would have 1 rotatable bond only? What about symmetrically para-substituted biphenyls?

Well, let's see how far I get with my definition:


phenylbenzene: 1 rotbond


1,4-diETHYLbenzene: 1 rotbond (the 1,4-diMETHYLbenzene is the rigid unit)


propanenitrile: 1 rotbond


I know I define rather rotatable units than bonds but I am not sure whether this is more accurate overall...?





Lorenz

I understand your approach, it is interesting. Can you specify a general definition for the rotatableUnitCount() function?





I am afraid, however, that this calculation would be computationally more demanding thank the current one resulting longer execution time. The current calculation gives similar results in most cases, and time is often critical, such as in case of database filters like bioavailibility.

Gyuri wrote:

I understand your approach, it is interesting. Can you specify a general definition for the rotatableUnitCount() function?

Hi





Well I am still not sure about this "unit" idea. Today I searched literature. What I found are about 3 different definitions for rotatable or flexible bonds, not really satisfying. I'll think that over, you'll hear from me later.





Lorenz

 

Hi everybody!

Gyuri wrote:

Hi Simone, Thank you for the good comment! Currently, Topology Analyser considers the following bonds as NON-rotating ones: - non-single bonds - bonds to hydrogens - bonds to terminal atoms (CH3, NH2, etc) - ring bonds - bonds of amides, thioamides, suplphonamides - bonds connecting aromatic rings having 3 ortho substituents - bonds connected to the terminal triple bonds (like cyano) is already implemented for the next release version 5.1, it has not been released yet What other rules do you propose? Gyuri

has the list of non-rotating bonds been changed since this post?

Thank you very much in advance!

Cheers,

Dimitris

Hi, 

No, there were no changes in the list on non-rotatable bond types. 

Best regards, 

Daniel