Atom lists, not lists

It is possible to define the type of an atom in a custom atom list. If the type of the corresponding atom in the target molecular structure is a member of the list, it is considered a matching atom (Table 1). Not lists can be used to specify atoms to be excluded (Table 2). Please note that the matching of not list atoms may depend on the input format of the query molecule. See details.

Table 1. Atom lists

Table 2. Atom not lists

Generic query atoms

Applying atom lists and not lists is a practical solution when the number of included or excluded atoms is small. However, generic query atom types are helpful to avoid long atom lists. JChem handles at the moment the following generic query atom types. For differences between matching any atoms appearing in different file formats, see here.

 A           Any (any atom except hydrogen. Neither matches to explicit nor
                 implicit hydrogens. Please note that in JChem the SMARTS primitive "*" is imported as any atom and does not match to plain hydrogens. (Neither explicit nor implicit.)) AH          Any atom, including hydrogen.
 Q           Hetero (any atom except hydrogen and carbon)
 QH          Hetero atom or hydrogen (any atom except carbon)
 M           Metal (contains alkali metals, alkaline earth metals, transition metals, actinides, lanthanides, poor(basic) metals, Ge, Sb and Po)
 MH          Metal or hydrogen
 X           Halogen (F,Cl,Br or I)
 XH          Halogen or hydrogen
 Gn          Member of group (column) n in the periodic system (n = 1..18)
                 Attention: G17 is NOT the same as X, as it contains At!
 *           Star atom, has the same meaning as AH query atom.

Table 3. Generic query atoms

Atom properties

The chemical neighborhood of an atom is sometimes as important as its type. Conditions for the chemical environment of an atom can be defined by atom properties (Table 5). Some of these require a value (connections, smallest ring size) others don't (aromatic). The smallest set of smallest rings (SSSR) is used for the evaluation of ring properties.

    a           aromatic (has aromatic bond)
    A           aliphatic (does not have aromatic bond)
    D<n>        Equivalent to s<n>
    H<n>        total hydrogens (total number of hydrogen substituents *)
    h<n>        implicit hydrogens (number of implicit hydrogen substituents)
    R<n>        rings (number of rings the atom is a member of)
    r<n>        smallest ring size (size of the smallest ring the atom is a member of)
    R           ring membership (whether atom is part of a ring or not)
    v<n>        valence (total bond order)
    X<n>        connections (number of substituents including hydrogens)
    s<n>        substitution count (number of non-hydrogen substituents
                plus number of isotopic hydrogen substituents)
                s0-s5: exact substitution count; s6: 6 or more substitutions
    s*          substitution as drawn (no extra non-hydrogen and no extra isotopic hydrogens)
    rb<n>       ring bond count (number of ring bonds next to the atom)
                rb0, rb2-rb3: exact ring bond count; rb4: 4 or more ring bonds.
                The same property can be achieved using the SMARTS "x" property (see smarts doc).
    rb*         ring bond count as drawn (no extra ring bonds)
    u           unsaturated atom (atom has double, triple or aromatic bond)

* Corresponds to both MDL and Daylight behaviors, depending on the source of the Molecule object. For details, see the differences section.

Table 4. Atom properties

Isotopes, charges, radicals

Isotopes, charges and radicals are atom properties which can be found not only on the query structure, but on a target as well. They are considered during the search. This includes that an atom without isotope, charge and radical information will match to atoms with information about those properties. However, this behavior can be fine-tuned using the following options:

• setOption(OPTION_CHARGE_MATCHING, CHARGE_MATCHING_DEFAULT / CHARGE_MATCHING_EXACT / CHARGE_MATCHING_IGNORE)
  (Cartridge: charge:d/e/i jcsearch: --charge:d/e/i)

• setOption(OPTION_ISOTOPE_MATCHING, ISOTOPE_MATCHING_DEFAULT / ISOTOPE_MATCHING_EXACT / ISOTOPE_MATCHING_IGNORE)
  (Cartridge: isotope:d/e/i jcsearch: --isotope:d/e/i)

• setOption(OPTION_RADICAL_MATCHING, RADICAL_MATCHING_DEFAULT / RADICAL_MATCHING_EXACT / RADICAL_MATCHING_IGNORE)
  (Cartridge: radical:d/e/i jcsearch: --radical:d/e/i)

(All constants above are defined in class chemaxon.sss.SearchConstants.)

The following tables show some examples.

Table 5.

Table 6.

Table 7.

Link nodes (link atoms)

Link nodes are atoms which may occur one or more times defining a variable length chain or ring. The link node is denoted by its brackets and the repetition range. All bonds not crossed by the brackets (and connecting parts) are also repeated together with the link node. See examples below.

Table 8.

Repeating units

Repeating units represent structural parts that can be repeated several times. The repeating unit is enclosed in brackets with one or two head and the same number of tail crossing bonds. (Head crossing bonds go through the left bracket.) Two bond pairs represent ladder type repeating units. The repetition range is a comma-separated list of possible repetitions or repetition intervals, e.g. "1,3,5-9". The repetition pattern specifies the way how the subsequent repeated units are linked together: it can be head-to-head(hh), head-to-tail(ht) or either/unknown(eu) (the either/unknown case is not handled by the search software). In case of ladder type polymers there is also a flip(f) option that defines that the top and bottom crossing bonds are flipped during each connection.

Table 9.

Table 10. Substructure search examples

Undefined R-atoms

An undefined R-atom is an R-group without definitions. (For the description of defined R-atoms, see R-group query structures .)

By default, undefined R-atoms can match atom groups including one or more heavy atoms or a hydrogen isotope. Hydrogen isotopes are handled as non-hydrogen atoms: they are forbidden at blocked positions and considered as heavy atoms when matching undefined R-atoms.

The matching behavior of undefined R-atoms can be altered using the undefinedRAtom option:

        g   Default: Undefined R-atom matches a group of
            one or more connected atoms in target,
            including at least one heavy atom.
        gh  Undefined R-atom matches a group of
            one or more connected atoms in target,
            which can also be a single H atom.
        ghe Undefined R-atom matches a group of
            one or more connected atoms in target,
            which can also be a single H atom or the empty set
            (empty set match is allowed for isolated or
            one-attachment R-atoms only).
        a   Undefined R-atom matches any single atom in target.
        u   Undefined R-atom matches only an undefined R atom in target.

Notes:

• g, gh, and ghe options are not supported in case of R-group queries of Markush targets.

• If group matching is switched on (options g, gh, or ghe) and at least one undefined R-atom is present in the query, then substitution is blocked at all other positions. In other words, this means that a full fragment matching is performed even if otherwise substructure search was specified. (Note, that in case when there is no undefined R-atom in the query, individual positions can be blocked using the s* query property.)

Table 11/A. Examples with default settings

There are two more options which affect the R-atom group matching behavior:

• bridgingRAllowed (n/y): if switched on (y) then different R-atoms are allowed to match the same group of atoms (default: switched off (n)).

• RLigandEqualityCheck (y/n): if switched on (y) then R-atoms with the same R-group ID should match ligands with the same structure (default: switched on (y)).

Note, that bridging R-atom matches are also ligands having the same structure.

Table 11/B. Examples with specific options

When undefined R-atoms matching is group matching and hydrogen with or without empty set matching is also allowed (options gh, ghe ), then for each undefined R-atom the possible matching atom groups are sorted by the following order of precedence:

1. group or isotope hydrogen

2. explicit hydrogen

3. implicit hydrogen

4. the empty set

This ordering is done locally when a scaffold matching is extended by group matchings in place of the undefined R-atoms.

However, if the --hitOrdering:g parameter is set, then this ordering is global over all search hits, in the order of R-atom numbers (R1 atom matches are considered first, then R2 matches, etc.). For example, if there are R1, R2 and R3 R-groups then the sorting algorithm will try to match R1 to a heavy group if possible, otherwise a H-atom and finally to the empty set; then the same is played with R2 and then with R3.

Limitations when undefined R-atoms are matching group (options g, gh, ghe ):

• The query is not allowed to have two adjacent undefined R-atoms or an undefined R-atom adjacent to a homology group.

• Undefined R-atoms adjacent to H atoms only are not allowed.

• Query features on undefined R-atoms are not allowed.

• Double bond stereo involving undefined R-atom is not allowed.

• Undefined R-atom as chiral center is not supported, but it can be adjacent to chiral centers. Examples:

  not supported	supported

• The "rb*" query property is ignored on all atoms in the query.

• SMARTS atom / bond properties referring to the query may not be processed correctly.

• Search is always processed in order sensitive mode.

SMARTS atoms

JChem's search supports all valid SMARTS atom expressions. (See Daylight's SMARTS theory manual.)

SMARTS atoms are depicted the following way in Marvin:

The following additional query features are handled as part of this:

Pseudo atoms

Pseudo atoms have user-defined atom types, and they only match another pseudo atom of the same name (case insensitive). Commonly used pseudo atoms include "Resin" and "Pol", referring to the often used solid phases in syntheses (Pol is the default pseudo for resin in MDL ISIS/Draw).

Table 16.

It should be noted that there is no chemical intelligence associated with pseudo atoms. This means that if a common abbreviation is used as pseudo atom, it will not match the corresponding molecular group. To achieve this, correct abbreviations (Superatom S-groups) must be used.

Homology (generic) groups

Some pseudo atoms represent homology groups, which refer to specific chemical classes. Examples are alkyl, heteroaryl, protecting, etc. (see complete list) From JChem version 5.3 homology groups are supported on the query side. Target side handling was already implemented in version 5.1. Query side homology searching uses the same homology definitions as the target side except a few cases. Query side homology handling does not require any special licenses beside JChemBase or changing search options from the default behavior.

Lone pairs

JChem search can handle query and target atoms having lone pairs associated with them. Lone pairs on the query side match explicit and implied lone pairs, but please note that lone pairs are only considered when attached to an atom, i.e. isolated lone pairs will not match anything.

Table 20.

Generic bonds

Querying against bonds can determine if a bond in the target molecule is one of the four basic types (single, double, triple, aromatic) or one of the generic types that are available for fine tuning query structures (Table 6). The line style represents the type of a bond.

Table 21. Generic bond types

Note on aromatic bonds

For the correct use of aromatic bonds and aromatic systems in general, see the Aromatization section under Standardization JCB .

Chain/ring bond attributes

In addition to the bond type discussed above, a bond topology query attribute can be assigned to bonds. This expresses that the bond must be part of a ring or must not. See the examples below.

Table 22. Generic bond types

SMARTS bonds

SMARTS bond expressions are also supported. (See Daylight's SMARTS theory manual.)

SMARTS bonds are depicted the following way in Marvin:

Like at SMARTS atoms, SMARTS logical operators "!" (not), "&", ";" (high and low precedence and), "," (or) can be used. "&" is the default operator, hence "and" is assumed if there is no operator between two SMARTS primitives. Furthermore, the following characters have valid meanings:

Table 23.

Table 24.

Table 25.

Further SMARTS examples can be found on Daylight's page.

Coordinate bonds

Coordination compounds MS can be registered and searched for in JChem structure databases. Both "atom to atom" and "multicenter" (involving more than two atoms) representations are supported.

Position variation bonds

Position variation bond (or variable point of attachment) is used to express that a bond may be attached to multiple positions (atoms), most often used for rings. This is represented by a multicenter atom at one or both end of the position variation bond. Its representation and drawing is described in the Marvin Sketch help and in Marvin JS help . See examples below.

Table 28. Meaning of position variation.

Table 29. Matching of position variation queries.

SMARTS component level grouping

This feature uses components as atoms connected by bonds. In SMARTS queries it can be specified whether different components (fragments) of the query should appear in the same or different components in the target. It is represented by grouping parentheses around the component in the SMARTS string. Please note that there is no graphical representation of this feature in Marvin.

Table 30.

Table 31.

Component, Mixture and Formulation brackets

This feature relates to the use of brackets (S-groups) of type COM (component), FOR (formulation) and MIX (mixture). A component here is a set of atoms contained by a component bracket.

Other component features

During reaction searching, reaction component grouping is maintained; see at the reaction component handling section.

Full fragment matching ensures that all query components (atoms connected by bonds) match only full components. See its description in the Search types section.

Attached data in duplicate search

To help represent new molecular features during duplication control, from JChem 5.3 duplicate search uses special attached data with name starting with "[DUP]". These attached data names are automatically checked during duplicate searches (in exact mode).

Table 39. Example: Special attached data checking during duplicate search (differentiating enantiomers of helicene)

"Helicenes are notable for having chirality while lacking both asymmetric carbons and chiral centers.
Helicenes' chirality results from the fact that clockwise and counterclockwise helices are non-superimposable." ( Wikipedia )