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ChemDraw QueriesChemDraw Queries Webinar

Jesse GordonJesse GordonDirector of Software Marketing [email protected](617) 320-6989Skype: jessegordon

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Skype: jessegordon

July 15, 2009

ChemDraw Query Webinar outline

1) Setup ChemFinder for queries

2) Variable bond queries

3) Stereochemical bond queries

4) Points of attachment4) Points of attachment

5) Variable atom queries

6) Oligomer searches6) Oligomer searches

7) Atom type queries

8) Atom substituent queries

9) Atom property queries

10)Reaction queries & formula queries

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1. Setup ChemFinder for queries

In ChemFinder, we set up a search database of 60 molecules….

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Setup ChemFinder for download

• We'll substructure-search in ChemFinder for each query type.

• For each query, we'll describe how to draw the structure in ChemDraw

• Then we’ll see which substances match and don't match in ChemFinder

• Database is available on our website in ChemFinder format…

• Plus SDF, XLS, and CDX formats for summary.

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Setup ChemFinder for search

• Format for this webinar: (all substructure searches unless otherwise indicated)

OHSearch for… Locates…. Does NOT match…

X

Substructure search locates any isotopes, but if you specify a double bond that’s not a substructure of a single bond Indouble bond, that s not a substructure of a single bond. In reverse, specified isotopes are NOT a substructure of the natural isotope substance; and cyclopentane is NOT a substructure of cyclopentadiene

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substructure of cyclopentadiene.

2. Querying Variable Bonds











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Variable bond queries: S/D

S/DS/D

Search for… Locates…. Does NOT match…

S/D

S/DS/D

S/D

S/D

You can specify a variable bond: “S/D” for single or double. That will locate both cyclopentanes and cyclopentadienes,but NOT aromatic structures!but NOT aromatic structures!

NOTE: The “S/D” text appears in ChemDraw but by default is not shown in ChemFinder. To show the “S/D” text in ChemFinder, right-click on bond then “Show Query Indicator.”The same applies to atom queries; they too are not shown in ChemFinder by default

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The same applies to atom queries; they too are not shown in ChemFinder by default.

Variable bond queries: S/A, D/A, Any

Search for… Locates…. Does NOT match…HN

Other variable bonds: “S/A” single or aromatic (not double bonds!)S/A single or aromatic (not double bonds!)“D/A” double or aromatic (not single bonds!)“Any” means single, double, or aromatic(No match to acyclics heteroatoms nor other ring sizes)

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(No match to acyclics, heteroatoms, nor other ring sizes)

Variable bond topology: Chn


The “Chn” specification limits searches to chains. Substructure itself must be a chain even if attached to a ringSubstructure itself must be a chain, even if attached to a ring.Can be combined independently with S/D/A or other aspects.

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Variable bond topology: Rng, R/C


R/C R/C

The “Rng” specification limits searches to rings. “R/C” ith i h i“R/C” means either rings or chains. Does not match aromatics because bond order is different!

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Variable bond type combinations


R/C/Any and S/D/A/Any can be combined independently.

Other Variable Bond Types: Dashed Double bond: AromaticDouble Either Bond: cis or trans

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Double-dashed Bond: Tautomeric

Dative bond queries


HS

O

O

HS

Dative bonds are a type of double bond (with electron donation).Hence searching for a single bond does not match a dative bond;and searching for a double bond does locate a dative bond.

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gIncorrectly drawn dative bonds (in blue) don’t match.

3. Querying Stereochemical bonds











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L- and D- enantiomers

OHO

OHO

Search for… Locates…. Does NOT match…OH

O

(R)

OH(S)

(R)

O

HO

(S)

OH(R)

HO

(S)

HOOH

HO

HO

OH OHOHO

L-ribofuranose (natural)

HO

D-ribofuranose (synthetic)

OH

HO

O

HO OH

HO

O

HO

Searching for L-ribose (the natural isomer)does not locate the corresponding D-isomerdoes not locate the corresponding D isomer.

It does locate both the L-- & L-- conformers (blue), as well as the “unspecified” wavy bond version

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as well as the “unspecified” wavy-bond version.

Stereochemical specificity

Search for… Locates…. Does NOT match…L- -ribofuranose L- -ribofuranose

L- -ribofuranoseL- -ribofuranose

L-ribofuranose L- -ribofuranoseL ib f D-ribofuranose

OHO

L- -ribofuranose

L ribofuranose L- -ribofuranose D ribofuranose

OH

HO

HO

L ribofuranoseL- -ribofuranose

L-ribofuranose anomerD-ribofuranose anomer

If the enantiomer is specified, ChemFinder won’t locate the opposite enantiomer.If the enantiomer is unspecified, ChemFinder will locate both enantiomers. You can search with all chiral centers unspecified and all enantiomers are located

HO

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You can search with all chiral centers unspecified, and all enantiomers are located.

Cis- and trans- stereoisomers


Searching for cis- and trans- isomers is stereo-specific:If you search for one form, only that form is found;if you search for a variable form (using the “double either” bond),

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if you search for a variable form (using the double either bond), both forms are found.

Other stereochemical representations

There are two additional methods for representing stereoisomers and hence for stereochemical queries.

First, the “Query” toolbar contains three symbols:• Rac: A racemic mixture. • Abs: A pure enantiomer of known configuration.Abs: A pure enantiomer of known configuration.• Rel: A pure enantiomer of unknown configuration.

Second, the “Atom Properties”Second, the Atom Properties attributes include enhanced stereochemistry:

Absolute / Or / And

(access Atom Properties by

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right-clicking on an atom)

4. Querying Points of attachment











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Variable attachment - searching


• The variable attachment point above means the bromine atom i h d h 2 3 4 6 bis attached to the 2-,3-,4-,5-, or 6-carbon.

• The 1-carbon was not selected as an attachment point, so that (invalid) structure is excluded from the searchso that (invalid) structure is excluded from the search.

• “Expand generic search” eliminates 5-bromophenol as chemically identical to 3-bromophenol

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as chemically identical to 3 bromophenol.

Variable attachment - drawing

How to draw a variable point of attachment…

• Select the 2-,3-,4-,5-, or 6-carbon on the phenol molecule

• Avoid selecting the 1-carbon and the oxygen, or they will become attachment points as well!

• An asterisk “*” appears centered among the selected carbons

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• An asterisk appears centered among the selected carbons. Draw a single bond from the asterisk, then add Bromine.

Multi-center attachment - searching


Ferrocene contains a multi-center attachment, but most databases contain other drawing forms.

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Hence searching for an “associated” iron atom works best.

Multi-center attachment - drawing

Drawing multi-center attachment is analogous to drawing variable attachment.

• Ferrocene contains a multi-center attachment, representing a -bond from the Cp rings to the iron atom in C H Ferings to the iron atom in C10H10Fe.

• Not a variable attachment – that would be C10H8Fe, with two covalent bonds.

• However, many databases contain ferrocene with one covalent bonds from Fe to Cp, 5 l t b d t h C ior 5 covalent bonds to each Cp ring.

• Hence searching for an “associated” iron atom, with no bond at all, locates all forms.

• You can apply “bring-to-front” and “send-to-back” (on Object menu) to bonds so that

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the -bond appears behind the upper Cp ring and in front of the lower Cp ring.

5. Querying Variable atoms











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Variable halogen queries

Search for… Locates…. Does NOT match…F Cl

BrX

Br I

Br

[F, Cl, Br, I]F Cl

Br I

Cl

Searching for “X” is equivalent to searching for “[F, Cl, Br, I]”Other variable atoms: X: any halogenOther variable atoms: X: any halogen

M: any metalQ: any heteroatomA: any atom

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R: specified list

Atom lists and NOT-lists


• Atom list [brackets] can include hydrogen or any heteroatoms.

• Bracketed list can also include groups or nicknames, like [NO2, Me, OH]

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• “NOT-Lists” can specify which atom to exclude.

Variable metal queries


MFe Os

OM OsFe

Variable atom “M” searches for any metallocene• Variable atom M searches for any metallocene(ferrocene, osmocene, etc).

• Better to search without bonds, since catalogs differ in how they represent ll ( l d b h d l f f )

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metallocenes (our sample database had only one form of osmocene)

6. Querying Oligomers











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Oligomer queries


Polymers can be drawn “analytically” (as above, which searches correctly) or “representationally” (which is not reliable for searching)

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reliable for searching).

Oligomer generic expansion

R-groups can be used to represent oligomers analytically…

The oligomeric structure above is interpreted as three molecules viainterpreted as three molecules via “Expand Generic Structure.”(so is the oligomer to the left, but that form only applies to CH units)

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that form only applies to CH2 units)

Polymer representations

Representational form of oligomers and polymers:

• Polymers can be drawn with brackets, but these are representational only – appropriate for publication but not for database queries.

• To draw brackets, use Bracket Tools on main toolbar, then right-click for “SRU”.

• To draw the analytical forms (appropriate for searching):

• To draw CH2 list, start with glycine and type manually.

• To draw R-groups, use Query tools for R-box, then Chemical Symbol tools for attachment points

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then Chemical Symbol tools for attachment points.

7. Querying Atom types











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Charged atom queries


• Searching for an uncharged atom locates both charged and uncharged. • Searching for a charged atom only locates similarly charged atoms.

Ci l d h (f S b l M ) t At P t h

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• Circled charges (from Symbols Menu) act same as Atom Property charges,

Radical atom queries

Search for… Locates…. Does NOT match…2+ 2+

:NN

(diradical, notl i )

+2

2+:N

electron pair)

• Electron pairs are drawn from the Symbols menu; no affect on queries. • Radicals and diradicals are drawn from Atom Properties; they affect queries.

Q f l t i d t l t di di l lth h th l k lik

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• Query for electron pairs does not locate diradicals although they look alike.

8. Querying Atom substituents











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Atom substituent property

• Substituent propertiesspecify the number of substituents bonded to the selected atoms. p y

• “Substituent” is defined as:a non-hydrogen atom connected by a bond of any order.

• Unspecified: This is the default. The target base determines the search.

• Free Sites: Finds compounds in which the selected atoms contain a range of substituents up to the number specified plus the number of bonds as drawn. A value of zero finds a substituent count as drawn.

• Up to: Finds compounds in which the selected atoms contain a range of p p gsubstituents up to the number specified.

• Exactly: Finds compounds in which the selected atoms contain the exact number of substituents as specified.

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p

Exact substituent count property


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X indicates “Exactly X Substituents”, 0 to 15

Up To constituent count property


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U indicates “Up to U Substituents”, 0 to 15

Free Sites atom property


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Asterisk indicates “Free Sites”, 0 to 15, from Atom Properties

9. Querying Atom properties











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Query by Ring Bond Count


Note that the “R” does not indicate which ring0: no ring bonds2: simple ring

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Note that the R does not indicate which ring bond count is specified, so you must use a note!

2: simple ring3: fusion ring4: spiro ring

Query by Implicit Hydrogen

Search for… Locates…. Does NOT match…H

DD

DD

• The “H” symbol means “Implicit Hydrogens Not Allowed”.

• The default “Implicit Hydrogens Allowed” is not marked with “H”.

• Lacking hydrogen can be methyl, rings, or any atom.

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• Deuterium counts as hydrogen for this search.

Query by Unsaturation

Search for… Locates….S

S

Unsaturation must be absent

S

Unsaturation must be present

Unsaturation must be absent

S

• The “S” indicates that unsaturation must be absent or present. Unsaturation must be present

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p• Query works for ring structures as well.

10. Querying Reactions & Formulae




4) Points of attachment

Beyond the scope of this webinar;for “preview” purposes!

Some are for specialty databases4) Points of attachment


6) Oligomer searches

Some are for specialty databases and some are new in version 12; so look in your email for upcoming ChemBioClips!

6) Oligomer searches





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Formula Queries

Query… Locates….C6H6 compounds with 6 carbons and 6 hydrogen atoms,C6H6 compounds with 6 carbons and 6 hydrogen atoms,

plus any number of other elements.

=C6H6 compounds with 6 carbons and 6 hydrogen atoms and no other elementsand no other elements.

C6N0 compounds with 6 carbons, no nitrogens, plus any number of other elements.p y

C6 N1-3 compounds with 6 carbons and one to three nitrogen atoms, plus any number of other elementsplus any number of other elements.

Version 12’s formula queries allow equivalent of substructure searches!All of the above work with special atoms (e.g. C6X1-6 for halobenzenes)

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All of the above work with special atoms (e.g. C6X1 6 for halobenzenes)(Version 11 does some of the formula queries listed above, but not all).

Find Structure menu

Generic searches for chemical attributes:• Reactions—separated from single compounds • With Stereo Centers—tetrahedral but unspecified. • Missing Stereochemistry• Charged Charged• Radical• Isotopic Labels

• Query Structures—any generic variability such as:- generic atom types (R, A, M, Q, X)- atom types (Alkyl, Aliphatic, EDG, EWG)yp ( y p )- bond types (single-or-double, etc.)- element lists ([C,N,O])- ring bond count

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This is a new menu item in Version 12 ChemBioFinder.

Query by Classes

Query by chemical classes:• Hydrocarbons (H & C only)y ( y)• Aliphatics (acyclic)• Alicyclics (aliphatic rings)• Aromatics (4n+2) Aromatics (4n 2)• Antiaromatics (4n)• Natural products (C with N or O) • Alkaloids (MW>200 with basic N) Alkaloids (MW>200 with basic N)• Heterocycles (rings with N,O,S,P)• Organometallics• Inorganics• Inorganics• Salts

This is a new submenu in Version 12 ChemBioFinder

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This is a new submenu in Version 12 ChemBioFinder.

ChemDraw Query Webinar Summary











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onsons July 15, 2009

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