Aziridine

I like this molecule and I want to talk about it.

Aziridine is a small molecule that has similar characteristics as epoxide. But I have never seen this ring system before naw was it taught in any organic chemistry class I have seen until recently when I decided to take another. See if I still got it after 5 years.

Aziridine can be used as an electrophile that can extend functionality of a fragment with two carbons and a functional primary amine on the end to allow for functional group expansion or synthesis.

Aziridine, though, has been skyrocketing in popularity with emerging covalent warheads coming out because it is a great michael acceptor to be attacked by a cysteine and form a covalent bond between the sulphur and the and the carbon.

Because of this utility Aziridine is actually an important ring system that is emerging. Similarly, in CGenFF, it was left unaccounted for meaning this was chemical space that was unexplored and it failed so this made it a prime candidate for me.

If I write the Aziridine SMILES:

N1CC1

Look at the CGenFF output of just the charge because that’s all we need:

RESI *****          0.000 ! param penalty= 114.500 ; charge penalty=  75.385
GROUP            ! CHARGE   CH_PENALTY
ATOM N      NG311  -0.754 !   75.385
ATOM C1     CG3C31  0.020 !   53.524
ATOM C2     CG3C31  0.020 !   53.524
ATOM H1     HGPAM1  0.354 !    7.158
ATOM H2     HGA2    0.090 !    4.486
ATOM H3     HGA2    0.090 !    4.486
ATOM H4     HGA2    0.090 !    4.486
ATOM H5     HGA2    0.090 !    4.486

BOND N    C1  
BOND C1   C2  
BOND N    C2  
BOND N    H1  
BOND C1   H2  
BOND C1   H3  
BOND C2   H4  
BOND C2   H5  

END

Pretty easy, but NG311 seems too general when looking at this ring system especially with a charge that is almost a negative one meaning the dipole moment between the carbon. Take a look at the charge of the epoxide:

GROUP            ! CHARGE   CH_PENALTY
ATOM O      OG3C31 -0.400 !    0.000
ATOM C1     CG3C31  0.020 !    0.000
ATOM C2     CG3C31  0.020 !    0.000
ATOM H1     HGA2    0.090 !    0.000
ATOM H2     HGA2    0.090 !    0.000
ATOM H3     HGA2    0.090 !    0.000
ATOM H4     HGA2    0.090 !    0.000

BOND O    C1  
BOND C1   C2  
BOND O    C2  
BOND C1   H1  
BOND C1   H2  
BOND C2   H3  
BOND C2   H4  

END

In CGenFF but if I read this I can infer what atom types it should be because you can read the paper and learn the language. If I was to write this in the CGenFFAtom Type SMILES notation then it would be looking like this

N{NG3C31}1C{CG3C31}C{CG3C31}1

I think a three membered ring system of aziridine is very unique and worth it’s own atom type. Mostly likely to be added it would need the dedicated parameters.