Searrcchiing fforr Subssttanccess and Reaccttiionss iin Beiillsstteiin and Gmelliin 1
Table of Contents Scope of the Database 3 Searching by Structure 3 Introduction to the Structure Editor 3 Searching by Substructure 4 Assigning Free Sites 4 Assigning Topology 5 Assigning Bond Order 6 Using Generic Groups 7 Searching by Text 11 Using the Quick Search box 11 Using the tabular query grid 11 Reaction Searching 14 Basic Reaction Searching 14 Advanced Reaction Searching 15 Combining Searches 17 Searching for Structures and Text at the Same Time 17 Combining Hit Sets 17 2
Scope of the Database CrossFire Beilstein is the electronic version of the Beilstein Handbook of Organic Compounds. This is one of the largest database of organic compounds and reactions, containing more than 8 million fully characterized compounds and 9 million organic reactions. Data is taken primarily from the top 175 journals in organic chemistry, and references date back to 1770. Because it is a handbook, it is relatively easy to locate physical properties for the compounds included. Searching by Structure Introduction to the Structure Editor The main tools of the structure editor are listed below. The toolbar at the top of the screen allows you to select an atom, bond, or ring to add to your structure. The most commonly used organic atoms, bonds, and ring systems are listed. However, if you go to the atom pull-down menu, you can access any element from the periodic table. The bond pull-down menu has stereo bonds (up, down, and double-steric), in addition to bonds used in substructure searching. Please note that you can replace one atom or bond with another by selecting the new atom or bond, holding the shift key, and clicking on the undesired atom or bond. When you are finished, click the BC button to transfer your structure to the search screen. 3
Searching by Substructure Assigning Free Sites By default, the database searches for a structure exactly as you have drawn it, with all available valence filled with hydrogen atoms. If you wish to allow additional, non-hydrogen substitution at a position, you need to specify one or more free sites. Using the pencil tool, click on the atom to which you wish to add free sites. This will open the Atom Attributes menu. Use the up arrow beside the free site option to set a specific number of free sites (one, two, three, etc.). Use the down arrow beside the free site option to allow the maximum number of free sites for that type of atom. You can also set the valency of an atom, give it one or more positive or negative charges, specify a particular isotope by changing the mass, or convert a particular atom into a radical by using the up and down arrows beside the other atom options (below the Free Site option). 4
Assigning Topology Topology, in information retrieval, refers to the configuration of atoms in your molecule. There are two possible configurations: ring and chain. In a substructure search on Beilstein, the database searches for either topology by default. However, you can force the database to search for one or the other on individual atoms and bonds. For example, if you have the following structure C 2 C 1 you can force C2 to be chain only, excluding all structures in which C2 is part of a ring, such as the following two O C 1 C 2 C 1 C 2 To change the topology of a particular atom, click with the pencil on the atom in question, opening the Atom Attributes menu. Click on the pull-down menu beneath the word Topology. Select the appropriate topology by clicking on it. Click OK. 5
To change the topology of a particular bond, open the Bond Attributes menu by clicking on it with the pencil. Click on the pull-down menu beneath the word Topology. Select the appropriate topology by clicking on it. Click OK. Assigning Bond Order In addition to changing the topology of a bond, you can also change the bond order. This allows you to search for a particular bond order (single, double, triple) or configuration (up, down, steric unknown, double steric), as well as for multiple bond orders at once. For example, if you want to find either of the following compounds in a single search, O OH you can use the option Single/Double, which searches for either a single bond or a double bond at the specified position. Other options include Double/Triple, which searches for either a double or triple bond, and Any, which searches for single, double, or triple bonds. To employ any of these options, either select them from the pull-down menu at the top of the structure editor or click on the bond in question with the pencil to open the Bond Attributes menu 6
Using Generic Groups Generic groups are a way of specifying multiple possible substituents at a particular position without doing multiple searches. For example, you can tell the search engine that you wish to retrieve molecules with either phenyl or methyl attached to a particular carbon. You can choose to use generic groups that are pre-defined by Beilstein, or you can create your own group consisting of atoms or fragments that you draw. To use a generic group, select the Generics option from the atom pull-down menu. There are two sections to the generics menu. The Atom menu allows you to specify multiple atoms that could appear at a particular position. Pre-defined Generic Atoms include o A = any atom, excluding H o AH = any atom, including H (could also just use free site) o Q = any atom, excluding C and H o QH = any atom, excluding C o M = any metal o MH = any metal or H o X = any halogen o XH = any halogen or H 7
User-defined Generic Atoms allow you to specify particular atoms as part of your group. To use a User-defined Generic Atom, click on the up arrow next to A, and click the OK button. This makes A1 your active atom. Draw the A1 into your structure Click on the A n button on the left toolbar. Select A1, and click OK. A periodic table will appear To make an atom part of your generic, click on it in the periodic table. To define a row or a column, click on the row or column number. If you want to exclude an atom, row, or column, specify the atoms that you want to exclude, click on A1 with the pencil tool, and choose the "Exclude" option. If you want to include some atoms and exclude others, you need to use a generic group rather than generic atoms. If you wish to use an entire group or a group of fragments that you draw, you will want to use the Generic Groups section of the generics menu. Pre-Defined Generic Groups include o G = any group o GH = any group or H o ACY = acyclic group o ACH = acyclic group or H o ABC = carbacyclic group (may contain no heteroatoms) o ABH = carbacyclic group or H o AHC = heteroacyclic group (must contain at least one heteroatom) 8
o AHH = heteroacyclic group or H o ALK = alkyl group (carbons and hydrogens only; no multiple bonds or rings) o ALH = alkyl group or H o AEL = alkenyl group (carbons and hydrogens only; at least one double bond must be present; no rings or triple bonds) o AEH = alkenyl group or H o AYL = alkynyl group (carbons and hydrogens only; at least one triple bond must be present; no rings allowed) o AYH = alkynyl group or H o AOX = alkoxy group (defined as -O-ALK) o AOH = alkoxy group or H o CYC = cyclic group (must contain at least one ring) o CYH = cyclic group or H o CHC = heterocyclic group (must contain at least one ring, and at least one of the rings contain one or more heteroatoms) o CHH = heterocyclic group or H o CBC = carbocyclic group (must contain at least one ring and no heteroatoms) o CBH = carbocyclic group or H o HAR = heteroaryl group (at least one aromatic ring directly attached to parent molecule; at least one ring in the group must be a hetero ring) o HAH = heteroaryl group or H o ARY = aryl group (at least one optionally fused benzene ring directly attached to parent molecule) o ARH = aryl group or H o CAL = cycloalkyl group (carbons and hydrogens only; at least one ring directly attached to parent molecule; no multiple bonds in rings) o CAH = cycloalkyl group or H o CEL = cycloalkenyl group (carbons and hydrogens only; at least one ring directly attached to parent molecule; at least one double bond present) o CEH = cycloalkenyl group or H User-Defined Generic Groups allow you to draw fragments and group them as part of a generic. To create a User-Defined Generic Group, do the following. o Select Generics from the atom menu at the top of the Structure Editor, and use the up arrow next to G set the number of the G group (G1, for instance). o Draw the group into the molecule. o Draw the fragments or atoms that make up the group (note: this is the only way you can make a group that includes some atoms but excludes others). o Box the entire group with the selection tool, and click on the G n button at the left of the screen. o Select the number of the G group and click OK. The G group is now assigned. 9
o Now, you need to tell the fragments where to attach to the parent molecule. 10
o Using the pencil tool, click on the atom in the G group that you want to attach to the parent molecule. o From the atom option menu, select the "Attachment Points" button. A little number "ap 1" or "ap 2" will appear beside the atom(s) adjacent to the G group in your structure. Decide whether the atom in question should attach to point one or point two and put a check in the appropriate box. o Do not forget to put multiple points of attachment on a fragment that attaches to the molecule in more than one place. o You can specify the number of times a G group may appear in a molecule. Suppose you want a ring to have two substituents, A and B. You only want two positions on the ring substituted (maximum), but the substituents can be in any position on the ring. Specify A and B as your G group, placing the G group on the ring at all possible locations. To set the frequency, click on the G1: next to the boxed substituents. Searching by Text Using the Quick Search box The quick search box is located on the bottom of the screen, just below the structure search area. For a quick search of all data fields, type your search terms in the region below. By default, this search does an automatic AND of all terms. You can change this to OR by changing the operator in the pull-down menu. If you do not want the search to truncate all terms, turn off the automatic truncate feature by unchecking the box. Using the tabular query grid You can use the text search options to combine different pieces of information in a textual search. This allows you to search for specific compounds by formula, name, or registry number, to search for all compounds in the database that have particular physical properties, or to see if a particular quantity or property is available for a certain compound or type of compound. You can open the text query box by clicking the bar underneath the words Search Fields from the main Commander screen. The tabular query has four fields, Field Name, Relation, Field Value, and Operator. 11
The Field Name is the part of the record that you want to search. Examples of field names are CAS number, NMR, Journal Title, and Molecular Formula. You must use Beilstein s abbreviation for the name of the field. To find this abbreviation: Use the Search Fields tab in the left column of your screen. This brings you into a tree structure for searchable fields (ex. Chemical Name, CAS number, Spectra, Date of Publication Select the field that you want, either by clicking through the tree or by searching in the Search Field Name in Hierarchy option, just above the field tab. Double-click on a field name to add it to the table The Field Content is the text or number for which you want to search in the field that you have chosen. Examples of values that may appear in the chemical name field are benzene, 1-bromo-heptane, and buckminster fullerene. For fields whose values contain text rather than numbers, it is best to search the fields indices and locate the exact spelling of the text within them. Click on the downward-pointing arrow beside the field content space. This will bring you to the index for this field. Slowly type in the word for which you want to search. The index will scroll automatically to the proper place in the alphabet. Select a term either by clicking on it (to highlight it) and clicking on the double-arrow button or by double clicking the term. You may select multiple terms. Click OK to continue. 12
The Relation space tells the search engine how it should locate the field content within that field. Your choices of operator for text searches are is (an exact search), starts with (automatic right-handed truncation), ends with (automatic left-handed truncation), contains (truncation on both sides), and exists (the field exists in a record, but you do not want to specify a value to be found in it). For numeric searches, you may choose to use is (equals), <, >, <= (less than or equal to), or >= (greater than or equal to). Alternatively, when doing a numeric search, you can type the greater than/less than character within the search box or specify a range (ex/ 55-63). Use the Operator space only if you wish to combine your term with other terms. Beilstein has six operators. Four are very important. And allows you to search for both Term 1 and Term 2. Both terms must be present for a record to be retrieved. Or allows you to search for synonyms. A search for Term 1 or Tern 2 will bring forth records that have either Term 1 or Term 2. Not is the operator of exclusion. If you search for Term 1 not Term 2, you will retrieve all the records containing Term 1 that do not also contain Term 2. Proximity allows you to search for two terms within the same field of the record. If you search for Melting Point 1 proximity Melting Point Pressure 2, you will find only those records in which Melting Point 1 was taken at Melting Point Pressure 2. Placing a + sign in front of an operator is like using a parenthesis. When you search, the search engine will combine all terms whose operators have + signs before performing any other operations. 13
When you have finished adding all of your field names and values, click OK to close the text table and transfer your search statement into the Beilstein Commander. Click on the Start button in the Beilstein Commander to begin searching. Reaction Searching Performing a reaction search in Beilstein is very similar to performing a structure search, although you can also combine reaction searches with text in order to limit your reactions to those performed under particular conditions, employing particular reagents, or with a yield or range of yields that you specify. Basic Reaction Searching Draw the substances that you want to participate in your reaction into the structure editor. You can draw one or more reactants, one or more products, or a combination of reactants and products. Click on the Reaction Attributes button. This will take you into the reaction editor. Note that your drawing/editing options will change, and you will no longer be able to draw or edit atoms and bonds. If you wish to go back and edit your structures at any point, click on the Structure Editor button. Now, you need to assign reaction roles to your molecules or substructures. Using the marquis tool (highlighted on the screenshot below), draw a box around the structure whose role you wish to specify, and click on the Reactant or Product button. If you change your mind and want to change a molecule s role, select it with the marquis tool and click the Undefine button. Then, repeat the process to give it the desired role. 14
Click on the crossed red arrows to transfer your structures into the CrossFire Commander to run your search. Advanced Reaction Searching Once you have given all of your structures reaction roles, you can use some advanced search options that should help you narrow your search. Mapping atoms from reactant to product o Using the pencil tool, draw a bond from an atom in the reactant to the corresponding atom in the product. This is very useful when you are looking for substructures of larger molecules because it forces the chemistry to take place (or NOT take place) at the positions that you specify. 15
Defining reaction centers and specifying retention or inversion of stereochemistry o Another technique for forcing chemistry to take place at a particular site is to define a reaction center. You can do this by clicking on the atom at which you would like the chemistry to occur with the pencil tool. You will have the option to make it a reaction center, to forbid it from being a reaction center, or to leave it undefined. The default setting is undefined. This technique is very helpful if you are drawing a partial reaction but you know where the chemistry must occur. o You can use the same technique to specify stereochemistry within a reaction. If you want stereochemistry to be inverted or retained at a particular position, simply click on the atom with the pencil tool and select the correct configuration for your purposes. By default, it will find both cases. Specifying bonds to be made, broken, or changed o If you wish to specify that a bond in a reactant be broken, a bond in a product be made, or a bond s order or topology change, click on the bond in question using the pencil tool. It will invoke another menu that allows you to tell the system what chemistry will occur on this bond. This is another useful technique when drawing partial reactions. 16
Combining structures with text in a reaction search o Draw your reaction, assign reaction roles, and transfer it to the CrossFire Commander, using the crossed red arrow button. o Select the text tab labeled Search Fields from the left side of the Commander screen. Clicking on the + sign beside the words Beilstein PlusReactions should open a hierarchy structure. o There is an entire section related to reaction conditions in the Beilstein data structure. It is entitled Reaction Details. Clicking on any one of these details should give a description of what is included in that field. Use the text searching tips listed above to format a good search within the fields of interest. Combining Searches Searching for Structures and Text at the Same Time Searching for Structures and text at the same time is very easy. Simply draw the structure, substructure, or reaction for which you want to search in the Structure Editor (see Searching by Structure, above). Then, input the text that you want in the Text Editor, as described above. The word and will appear between them. If you wish to search for a structure but NOT a particular piece of text, see the section below, Combining Hit Sets. Combining Hit Sets Once you perform a search, the program saves all of your results in a hit set. You can combine this hit set with other search terms. From the Commander screen, select the tab on the left that says Hit Sets. You should get list of all your queries. Select the one you want to use by double-clicking it. This should put your hit set into the field name area. Select an operator with which to combine the two hit sets. Combine with other hit sets, as described above, or combine with field names and values, as described in the previous section. 17