SMARTS

    SMARTS can be thought of as an extension of this mechanism to represent variabilities and choices in the node and edge properties in this graph, i.e. a way to specify variable choices for any of the atoms or bonds in the molecule. Using SMARTS one can specify a pattern to search for.

There are 4 parts to understanding and creating a SMARTS expression:

• Logicals
• Specifying atom variabilities
• Specifying bond variabilities
• Recursive SMARTS

Specifying atom variabilities:

      X3   Y1       Z1
      |    |       /
      |    |      /
      |    |     /
X2----C----C----N
      |    |     \
      |    |      \
      |    |       \
      X1   Y2       Z2
 

The SMARTS CC[O,N]  will match ethanol or ethylamine. If we examine how, we see

anything in square braces is a description for 1 atom only
               __|__
              |      |
CH2----CH2----[OH,NH2]
               | ||
               | ||
          Oxygen ||
                OR|
                  Nitrogen
 

Expressions within [ and ] are therefore atom SMARTS expressions.

Atom SMARTS may appear wherever an atom may occur in a SMILES.

This SMARTS CC[O,N] is read as

Aliphatic Carbon singly bonded to
    an aliphatic Carbon singly bonded to
        an atom that is (a Nitrogen OR an Oxygen)

',' is a logical representing OR
Here's the complete list of logicals in their order of precedence in SMARTS
 

'a' signifies an aromatic atom in SMARTS

Using this information let us analyse a few atom SMARTS expressions

        an atom
         _|__
        |    |
        [!N&a] : an atom that is ( (NOT a Nitrogen)AND is aromatic)
        ||||           i.e. an aromatic atom that is not a Nitrogen.
       NOT|||
          |||
   Nitrogen||
           ||
         AND|
            |
            is aromatic

[N,C&a] : an atom that is ( a Nitrogen OR a ( Carbon AND is aromatic ))
                  i.e. a Nitrogen or an aromatic Carbon

The number of Hydrogens attached to an atom is expressed in SMARTS as H<n> where <n> is any number.
<n> is optional and is by default 1 when not stated.

Therefore
    [H1] represents any atom with 1 attached hydrogen

Using this construct let us try figuring out the atomic SMARTS below:

[NH1]  = [N&H1] = atom that ( is a Nitrogen AND has 1 attached Hydrogen )
                e.g. a secondary amine

[nH1] = [n&H1] = atom that (is an aromatic Nitrogen AND has 1 hydrogen)
            = a pyrrole Nitrogen

[C,n&H1] = atom that (
                            is a Carbon OR
                                is an aromatic Nitrogen AND
                                    has 1 attached Hydrogen ) (prior to applying logicals)

                    = atom that (
                           is a Carbon OR
                           (is an aromatic Nitrogen AND
                                has 1 attached Hydrogen) )

                    = atom that (is a Carbon OR is a pyrrole Nitrogen )

[C,n;H1] = atom that (
                            is a Carbon OR
                                is an aromatic Nitrogen
                                    AND has 1 attached Hydrogen ) (prior to applying logicals)

                = atom that (
                       (is a Carbon OR
                            is an aromatic Nitrogen) AND
                               has 1 attached Hydrogen )

                = atom that ( is a ternary Carbon OR is a pyrrole Nitrogen )

Here's the complete list of atom property symbols in SMARTS
 

SMARTS Atomic Primitives

Symbol	Symbol name	Atomic property requirements	Default
*	wildcard	any atom	(no default)
a	aromatic	aromatic	(no default)
A	aliphatic	aliphatic	(no default)
D<n>	degree	<n> explicit connections	(no default)
H<n>	total-H-count	<n> attached hydrogens	exactly one
h<n>	implicit-H-count	<n> implicit hydrogens	exactly one
R<n>	ring membership	in <n> SSSR rings	any ring atom
r<n>	ring size	in smallest SSSR ring of size <n>	any ring atom
v<n>	valence	total bond order <n>	(no default)
X<n>	connectivity	<n> total connections	(no default)
- <n>	negative charge	-<n> charge	-1 charge (-- is -2, etc)
+<n>	positive charge	+<n> formal charge	+1 charge (++ is +2, etc)
#n	atomic number	atomic number <n>	(no default)
@	chirality	anticlockwise	anticlockwise, default class
@@	chirality	clockwise	clockwise, default class
@<c><n>	chirality	chiral class <c> chirality <n>	(nodefault)
@<c><n>?	chiral or unspec	chirality <c><n> orunspecified	(no default)
<n>	atomic mass	explicit atomic mass	unspecified mass

Here are some atom SMARTS composed with these symbols.

  [#6] = a carbon atom

  [Ca] = a calcium atom

  [++] = any atom with a +2 charge

  [CH2] = atom that is (an aliphatic carbon and has two hydrogens)
                  = ( a methylene carbon)

  [35*] = any atom of mass 35

  [F,Cl,Br,I] = the 1st four halogens.

  [!C;R] = atom that is (( NOT aliphatic carbon ) AND is in a ring)
 

Bond Properties:

cc = c:c = any pair of attached aromatic carbons
':' is the symbol for an aromatic bond

CC = C-C = any pair of attached aliphatic carbons
'-' is the symbol for a single bond

c-c = 2 aromatic Carbons joined by a non-aromatic single bond
            e.g. as in biphenyl

Bonds can be variable as in atom SMARTS along with logicals e.g.

C-,=,#N = a Carbon bonded via a single or double or triple bond to
                a Nitrogen

C~N = a Carbon bonded via any bond to a Nitrogen
~ is the symbol for a wildcard bond

C@N = a Carbon bonded via a ring bond to a Nitrogen
@ is the symbol for any ring bond

N/?C=C/O     = N bonded via trans or unspecified chirality to a C double-bonded to a
                            C singly bonded to an oxygen

Here's a list of SMARTS primitives for bonds:
 

Hence one might represent a C ortho to a N via the SMARTS

CaaN = Carbon singly bonded to an aromatic atom bonded via an aromatic
                bond to an aromatic atom singly bonded to a Nitrogen.

CaaaN = C meta to an N

CaaaaN  = C para to N

Recursive SMARTS:

        an atom that is
         _______|________
        |                |
        [$(CaaN),$(CaaaN)]
        |_____|||______|
           |    |    |
           |    |    |
           |    OR   |
           |         |
           |         a Carbon meta to Nitrogen
           |
  a Carbon ortho to a Nitrogen
 

This is a recursive SMARTS, where in place of an atom property in an atom SMARTS one can use any logical SMARTS itself, with the rule that
a recursive SMARTS must always appear within the symbols '$(' and ')'.

The above SMARTS would read
atom that is ( ( a Carbon ortho to a N) OR ( A Carbon meta to a N))
 

• A non-recursive Atom SMARTS cannot include information about the atoms bonded to the atom,
• A recursive Atom SMARTS can include this information

A few examples follow:

Caa(O)aN = Carbon ortho to O and meta to N (but in a single path i.e. 2O,3N only)

Ca(aO)aaN = Carbon ortho to O and meta to N (but in differing paths i.e. 2O,5N only)

C[$(aaO);$(aaaN)]  = C ortho to O and C meta to N (all cases)
 
 

Component SMARTS:

A SMILES like

C.C would be 2 methanes

However its SMARTS meaning is a pattern that matches

2 aliphatic Carbons which may be in the same molecule or in different molecules, therefore matching ethane(CH₃CH₃) or propane(CH₃CH₂CH₃)

To restrict the Carbons to be in a single molecule, one can use the parentheses operators to group dot-disconnected fragments e.g.

(CC.C) would not match ethane, but would match propane or butane

(C).(C) would not match ethane propane or butane alone, since the 2 C's must come from differing components.
(C).(C) would match the SMILES CCCC.COC (i.e. CH₃CH₂CH₂CH₃ + CH₃OCH₃)

(CC).C would match butane  and propane since there is no restriction on the second Carbon

In SMARTS one might represent and (thereby match reactions representing) general esterifications as

C(=O)O.OCC>>C(=O)OCC.O     an acid and an alcohol in the reactant go to an ester and water in the product.

        O--H          Y2 Z1
        |            |  |
        |            |  |
   X2---C===O   + Y1--C--C--O--H
        |             |  |
        |             |  |
        X1           Y3  Z2
 

To convert this to represent and match intermolecular esterifications only
 

           in a separate mol
in 1 mol.  |
 __|___   _|_
|      | |   |
(C(=O)O).(OCC)>>C(=O)OCC.O     both acid and alcohol come from different
|            |  |        | molecules
 ------------    --------
      |               |
 in the reactant      |
                      in the product
 

To represent and match intramolecular esterifications only:

in 1 mol.
 __|_______
|          |
(C(=O)O.OCC)>>C(=O)OCC.O     both acid and alcohol come from the same
|           | |        | molecules
 -----------   --------
      |             |
 in the reactant    |
                    in the product
 
 

With the current state of SMARTS editors in order to use SMARTS powerfully a chemist needs to either

• be really good at composing SMARTS expressions or
• needs to have a good library of recursive SMARTS definitions that he/she can use to compose chemically intuitive queries.

Examples:
 

A hydrogen bond donor

An aliphatic polar atom such as Oxygen or Nitrogen or Sulfur having at least 1 hydrogen and not in a ring

= (aliphatic O or N or S) AND (having at least 1 Hydrogen) AND (NOT in a Ring)

an atom that is
 ______|_____
|            |
[O,N,S;!H0;R0]
  | | ||| ||_____not in a ring
  OR| |||_____________with 0 Hydrogens
    | ||__________NOT
    OR|
      |
      AND (Lower precedence than OR)
 

A halogenated phenol

=
                   an atom that is
 _______________________________|_____________________________
|                                                             |
[F,Cl,Br,I;[$(*[$(c1c(O)cccc1),$(c1cc(O)ccc1),$(c1ccc(O)cc1))]]
 |       ||
  ------- |
     |    AND (LOWER ORDER THAN OR)
a F OR Cl OR Br OR I

 
               an atom that is
 ________________________|________________________
|                                                 |
[$(*[$(c1c(O)cccc1),$(c1cc(O)ccc1),$(c1ccc(O)cc1))]
   | --------------| -------------| -------------
   |        |      |      |      OR        |
any atom    |     OR meta in a phenol      para in a phenol
connected   |
       ortho in a phenol

This can be further simplified to

[F,Cl,Br,I;[$(*c1[$(c(O)cccc1),$(cc(O)ccc1),$(ccc(O)cc1)])]
 

Now why can't the above be further simplified to:
 

[F,Cl,Br,I;[$(*c1[$(c(O)cc),$(cc(O)c),$(ccc(O))]cc1)]

Think and let me know your answer later.

A Primary or secondary amine and not an amide