A reaction based combinatorial library generation system has been used to generate theoretical libraries in Abbott. The program, written with Daylight reaction toolkit, requires the generic transformation to be coded in SMIRKS. However, it is difficult for a bench chemist to interconvert between a SMIRKS notation and a graphic representation. This limits the application usage to the power-users.
Two complementary approaches can open up the library generation program to bench chemists:
This presentation focuses on the latter solution.
Pre-defined SMIRKS can be saved as a string in a database, but it is not structurally searchable. In order for chemists to find a stored SMIRKS with a structure query, an indirect SMIRKS structure search has to be developed.
Reaction SMILES is structurally searchable. In combinatorial synthesis, it is always generated by a SMIRKS and, contains the atom map defined by the SMIRKS. This correlation can be used to bridge the reaction SMILES structure search to that of SMIRKS.
Structurally querying on the reaction SMILES is not always an accurate SMIRKS search.
In all cases, the valid SMIRKS is included in an answer set. By allowing a user to review the hits, the desired transformation can be selected.
SMIRKS is stored in a text field under the associated reaction SMILES entry in a Daylight reaction database. The indirect SMIRKS search is a shared library that
Client-Server & Model-View-Controller
RXNSearchServer creates an object SearchRXNServer to handle the Daylight reaction database search requests.
RXNSearch defines a native method that conducts the Daylight reaction database search.
SearchRXNImp.o is the implementation of the native method which uses the shared c library SearchRXN_Functions.o.
RXNSearchApplication is the Model, which communicates with the remote service SearchRXNServer.
RXNSearchPanel is the View.
RXNSearchActions is the Controller.