1.1 An Overview
ChemSpider
is delivered to you via a website and offers numerous tools of general value to
chemists. It allows you to search a chemical database containing millions of
chemical structures and various associated property information. The searches
can be based on alphanumeric text or chemical structure.
Also
available are a number of transactional services utilizing either structural
inputs or produce structural outputs.
The services available are:
· Generation of systematic identifiers – SMILES and InChI
strings
· Conversion of a systematic name, a trivial name, a registry
number, a SMILES string or InChI code to a chemical structure
· The
prediction of physicochemical properties based on ACD/Lab
algorithms
ChemSpider is integrated to two chemical
structure drawing applets – a Structure Drawing Applet and a PC-based drawing
package, ACD/ChemSketch. Both of these software components are
described in separate documentation and will not be discussed in detail in this
manual.
This chapter will familiarize you with
· Navigating
the ChemSpider website;
· General
information on the ChemSpider interface; and
· Features
available within the ChemSpider website.
To access ChemSpider enter www.chemspider.com into the navigation
entry box of an Internet Browser. ChemSpider has been rigorously tested on
Internet Explorer version 7 and exercised on Mozilla/Firefox. The Home Page
offers the route by which to navigate across the majority of the website. The
Navigation interface is illustrated below with descriptive annotations.
·
About ChemSpider - provides an overview about ChemSpider keeps
you updated with news and views
·
Search – This is the search interface to allow access to the
ChemSpider database
·
Predictions – Provides online access to structure based
predictions of systematic identifiers and physicochemical based predictions
·
Help and FAQ – Access to manuals and frequently asked questions.
This page will be updated on an ongoing basis
·
Contact us – Contact information for ChemSpider
· Spinneret
Webzine – Weaving the Chemical Web one molecule at a time (the writings of
David Bradley)
The ChemSpider search screen illustrated below allows
searching according to identifier, properties and calculated properties. Each
will be explained in detail.
2.2.1
Search by Identifier
The Identifier Search allows
searching of the database by five structure identifiers. These are systematic
names, trivial names, registry numbers of various types, SMILES codes and InChI
strings. These are defined in more detail below. If the “Match Full Name” box
is checked then the search will find the exact string only. If the box is not
checked then a search for the term “oxazole” will find all chemical names
containing that substring.
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Identifier Type
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Systematic Name – this includes two primary types of systematic
nomenclature – IUPAC names and Index (CAS-type) names.
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Trivial Name – this allows searching by one or more trivial or
trade names associated with a chemical structure.
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Registry Numbers – search on various registry numbers associated
with chemical structures
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SMILES strings – the SMILES strings listed in the database are
those generated using the ACD/Labs software.
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InChI strings – InChI strings are canonicalized by default.
Since all InChI strings utilize the InChI DLLs provided by IUPAC searching
should invoke a simple copy and paste into the search box.
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Some example identifiers for the same molecule are shown
below:
Systematic
names: 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Trivial names: Xanax
Registry numbers: 249-349-2 (EINECS Number),
28981-97-7
SMILES codes: Clc2cc3/C(=N\Cc1nnc(C)n1c3cc2)c4ccccc4
InChI strings: InChI=1/C17H13ClN4/c1-11-20-21-16-10-19-17(12-5-3-2-4-6-12)14-9-13(18)7-8-15(14)22(11)16/h2-9H,10H2,1H3
2.2.2 Search
by Properties
The Search by Properties search provides
the ability to search by one or more properties intrinsic to the
molecule. At BETA release it is only possible to
search on the exact molecular formula. The molecular Weight (Mw) and various
mass searches can be searched by “defect”, a common search method for
analytical scientists. Further details are given in the table below.
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Property Type
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Empirical Formula – A
molecular formula is a concise way of expressing information about the atoms that constitute a particular chemical compound.
For molecular compounds,
it identifies each constituent element by its chemical symbol and indicates the number of atoms of each
element found in each discrete molecule of that compound.
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Molecular Weight – The
molecular weight (Mw) of a substance is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12)
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Nominal Mass – The Nominal
Mass (Mn) of a molecule is the sum of the approximated monoisotopic masses of
the elements forming the molecule.
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Average Mass – The
Average Mass (Mav) of a molecule is the
sum of the calculated masses of the atomic weights of the elements from which
it is composed.
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Monoisotopic Mass – The Monoisotopic
mass (Mmi) for a molecule is the sum of
the exact masses of the most abundant stable isotopes that can occur
naturally.
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A common search that would
be executed by a scientist, especially a mass spectrometrist would be a search
on a monoisotopic mass with a defect. For example, 121.4536 +/- 0.0002 would
search for the mass of 121.4526 with a defect of 0.0002.
2.2.3
Search by Calculated Properties and Results Display
The Search by Calculated
Properties allows the user to search by one or more calculated properties
for the molecule. All properties provided in release version 1 of ChemSpider
use algorithms provided as part of a collaboration with Advanced Chemistry
Development (ACD/Labs). The search capabilities allow searches by the range of
a particular property and usage should be inituitive. Simply input the range of
the property for searching and click on the Search button. The search below
demonstrates a search on all molecules with a calculated value of logP between
3 and 4 (as predicted using ACD/LogP batch software).
The Results are shown initially in a tabular display
known as the Brief Display mode.
Alternative displays include the “More Details” mode
shown below
and the Single Record
mode shown below. The Single record mode shows the chemical structure, the
systematic names as generated by ACD/Labs nomenclature software, Trivial Names
and Registry Numbers if available, SMILES and InChI systematic identifiers and
intrinsic properties of the molecule.
Notice the shuttle buttons below the single record
allowing scrolling through all hits. From left to right the four shuttle
buttons are:
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BACK TO FIRST RECORD
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BACK ONE RECORD
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FORWARD ONE RECORD
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FORWARD TO LAST RECORD
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Notice that it is possible
to select either a Structure format for the Single Record Mode or a Properties
format. The Properties format displays a series of predicted properties
generated using the ACD/Labs PhysChem predictors. The Properties format is
shown below.
Notice that at the top of
the page is a button saying 
. Selecting this button will allow
the form containing the original search criteria to be shown. Similarly Hide
Search Form will remove the Search Form from the display in order to make
review of the results page easier.
2.2.4. Searching
Multiple Properties Simultaneously
It is possible to search on multiple properties simultaneously
as shown below.
The search above is a
simultaneous search of molecular weight, logP, Fule of 5 Failures, # of
hydrogen bond acceptors, number of hydrogen bond donors, number of freely
rotatable bonds amd polar surface area. Notice that in front of each property
is a check mark and all are selected by default.
This search produces five
hits, 2 are shown below.
The search can be expanded
simply by unchecking certain properties for the search. For example, removing
the constraint of PSA by checking the box provides 9 hits. Removing PSA and FRB
from the search gives 21 hits. This type of Boolean AND search provides a
powerful way to constrain the search.
2.3
Services Menu
The services menu provides tools allowing
·
generation of a structure from a name or identifier
·
drawing a chemical structure as an input to property generation
algorithms
·
prediction of various structure identifiers and physciochemical
properties using ACD/Labs algoithms
2.3.1
Generate Structure
The default
view when entering the Generate Properties window is shown below.
To generate a
structure from a systematic name, trivial name, registry number, SMILES or
InChI code simply type or paste it into the text box and click on the 
button.
Depending on whether the Image or Applet check boxes are selected the structure
will be displayed as an image or inside a structure drawing applet as shown
below.
IMAGE DISPLAY APPLET DISPLAY
If the choice is simply to draw a structure prior to generating the
properties simply select the applet and sketch the chemical structure into the
applet. For details regarding use of the applet consult the online manual or the reference guide.
Once the structure is drawn in can be saved to the desktop as a molfile
using the 
button.
2.3.2 Generate
Properties
Once a structure has been drawn or
converted from a chemical name or identifier generation of the list of
structure identifiers and calculated properties is as simple as clicking on the
button.
The resulting output is shown below. In certain cases the algorithms cannot
predict properties for certain molecules and in these cases will return the
results of Cannot calculate as shown below for Dielectric Constant.
2.3.3
Online Structure and Substructure Searching of ChemSpider
In order to search structures online there are a number of
workflows that can be followed. These will be outlined separately.
2.3.3.1
Searching Using SMILES or InChI
In order to search
ChemSpider using SMILES or InChI strings navigate to the Services page and
input the appropriate string and convert to the structure. When the structure
is generated use the Search ChemSpider button to search the database. Only the exact structure can be searched
in this manner.
2.3.3.2
Searching Using the Name
In order to search
ChemSpider using a name navigate to the Services page and input the appropriate
name and convert to the structure. When the structure is generated use the
Search ChemSpider button to search the database. Only the exact structure can be searched
in this manner.
2.3.3.3
Searching Using a Structural Input
In order to search
ChemSpider using a chemical structure navigate to the Search page and use one
of two options to input the structure.
A molfile can be loaded from
the desktop by using the Browse button to navigate to the appropriate
molfile. Once selected use the Load button to load the molfile. The
structure will then be displayed as shown below.
Alternatively select the
Applet button and sketch the structure into the structure drawing window.
Select the appropriate radio
button to choose either an exact structure or substructure search and then
click on the Search button. The result will be displayed in the usual Tabular
format by default as shown below. A substructure search of eugenol, shown
above, provides a set of structural hits as shown below. The nature of
substructure searches will be discussed in further detail in Section 2.3.
2.3.4
Desktop Structure/Substructure Searching and Property Prediction in ChemSpider
Searching of ChemSpider, or predicting
properties with ChemSpider via the ChemSketch interface can be very useful
since it can dramatically speed up the process of structure generation.
ChemSketch enables facile structure drawing in the interface simply through its
ease of use but it also enables conversion of SMILES strings and InChI strings
to structures prior to searching. For conversion of these identifiers simply
use the Tools>Generate menu item.
In the commercial version of
ChemSketch it is also possible to convert names from structures but the
freeware only allows structure drawing, structure from SMILES and Structure
from InChI as shown above. For further details about drawing structures we
reference you to the ChemSketch manual.
Once a structure is either
drawn or generated simply Click on the ChemSpider button on the top menu bar
(for this the websearch addon for ChemSpider needs to have been installed). The
button is shown below.
The dialog box shown below will
appear and the service of choice may be selected: either search the exact
structure against the database, search for the drawn substructure or predict
properties for the drawn structure using the ChemSpider Properties Service.
The results can be shown in
either a browser window such as Firefox or Internet Explorer or in a window
which pops up over ChemSketch as shown below. Choose the appropriate option as
to how you wish results to be displayed. The results of a property prediction
are shown below in a window which appears over ChemSketch.
From this window an operation of interest may be to search
the structure in the ChemSpider database.
When a substructure search is executed from the ChemSpider
interface the results will be displayed in the exact format shown in a
web-based search as shown below. This search used the structure of aspirin as
the basis of the search.
2.4
The Details of Substructure Searching
Substructure searches in
ChemSpider are based on a
substructural core with the flexibility of the substructure search being based
only on non-explicit hydrogens. For the structure of eugenol below the
structure has been expanded initially to show explicit hydrogens. A
substructure search using this molecule as the input will then assume that ANY
atom in any hybridization can be attached at the A
position.
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Eugenol
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Explicit
Hydrogens
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Any Atom
Substitutions
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With this basis for substructure searches some examples
of the structures obtained following a substructure search using eugenol as the
basis af the search are shown below. In both cases some of the A atoms are removed for ease of comparison and bonds
have been reoriented to more accurately represent the molecule under
comparison.
Example 1
Example 2
