The future holds electric dreams

The future of the laboratory notebook is electronic according to John McCarthy, as laboratories begin to look for a chemically aware central data storage facility

Inefficiencies in paper notebook documentation, poor paper notebook legibility, process compliance, and the need to improve R&D productivity through information re-use and collaboration is leading life sciences laboratories to seek a corporate electronic lab notebook (ELN) that fosters collaboration between scientists and project groups, drives efficiencies, and lowers costs.

Specifically, an enterprise, multi-disciplinary ELN offers labs a centralised data repository and infrastructure for capturing, accessing, and sharing experimental information while also supporting the diverse needs of different disciplines without extensive customisation. Customisable workflows complimented with fine-grained security enable scientists within and across project groups to take responsibility for individual parts of an experiment. Centralised document management, workflow focus, and information re-use in a secure infrastructure significantly enhance an outsourcing organisation’s ability and agility to adjust resources dynamically, collaborate effectively with global partners and contract research organisations, and accomplish more with less in today’s challenging R&D environment.

Figure 1:  Symyx Notebook’s chemical intelligence enables scientists to easily design and share single- and multistep, linear, and convergent reactions—and register all of the components and details of the transformation automatically to a corporate database.

As life science organisations increasingly rely on enterprise software like ELNs to manage information across the product development lifecycle, they have realised the importance of software that is chemically aware - capturing at the time of creation all known chemical information and properties in a fully searchable and re-usable format. Chemical intelligence in software enables scientists to render and register what they have made, accurately describe how they made it, store and associate other research information with it (such as test results and formulation and process development updates), and search and retrieve all of this information at any point in a product's lifecycle. Having accurately and consistently captured the chemical and biological information for registered compounds, scientists can then compare this information with similar compounds to advance research.

This makes the enterprise ELN the chemically intelligent hub for workflow applications and discovery data on the scientist’s desktop. By supporting reliable data capture, auditing, tracking, storing, sharing, and reporting, the ELN collects the “who, what, why, when and how” of an  experiment, method, or process, enabling the ready recall and reuse of important information by researchers throughout an organisation. Using the ELN, researchers can leverage prior work, managers can track projects, lawyers can document discovery history for patent disclosure/defence, and companies can generate corporate databases of experiments.

Figure 2: Material properties can be calculated from the chemistry and looked up via Symyx ACD.

For synthetic chemists investigating and designing New Chemical Entities (NCEs), the ELN must be built on a solid chemistry foundation that enables them to quickly draw precise chemical structures, reactions, and biologics. This underlying chemical and biologic intelligence facilitates and accelerates accurate compound registration and searching, as well as the production of publication-quality graphics.

The chemistry engine underpinning the ELN also needs to offer full reaction transformation capture and searching, enhanced representation of tetrahedral and geometric stereogenic centres, and support for polymers, mixtures, and complex formulations. By capturing the full transformation of a chemical reaction in a fully searchable format, for instance, scientists can re-use past successful transformations and apply these techniques to synthesising novel compounds, not just known compounds. Furthermore, when searching in-house or external commercial databases for useful chemical reactions, chemists sometimes search by the structure of the starting materials or products, sometimes by chemical transformations - and, if they are to minimise false hits in transformation searching, they need an ELN that supports advanced chemical representation and reaction searching. A system with these capabilities will retrieve exactly the reaction transformations sought, minimising false hits in transformation searching by reliably matching atoms in reactants with the corresponding atoms in products and specifying the mapping of atoms and bonds in functional groups. By storing real reactions, an ELN can deliver what synthetic chemists expect. ELNs that store reactions only as collections of structures and do not map the transformation information run the risk of providing incorrect results (false positives) when chemists conduct searches using transformation information.

Figure 3: Stoichiometry calculations enable scientists to select a limiting reagent (LR) for individual steps or first step and propagate calculations and amounts, including percent yield, automatically over multiple steps.

Finally, the ELN needs to support sophisticated chemical representation tools for manipulating structures and defining the cheminformatics business rules used to standardise structure queries, displays, and registration. Without facilities to normalise chemical data and avoid duplicate structure entry, resulting repositories of critical information quickly become unusable. An ELN that offers solid chemistry and biologics intelligence across this spectrum can help synthetic chemists gain essential knowledge of chemical reactions and the types of chemical transformations that are practical in the design of successful NCEs.

The intellectual property that gives one life science company competitive advantage over another often boils down to a chemical structure. Symyx software comprehends chemistry and delivers chemical intelligence at the right points in the workflow to speed routine research tasks, such as sourcing materials and designing syntheses and process development plans.

Nowhere is chemical intelligence more important than in an ELN. ELNs are rapidly becoming the focal point of a scientist's work day - the place where experiments are designed, executed, analysed, reported, and shared. ELNs are also where companies securely capture and protect their critical chemical intellectual property. As a result, ELNs are also the place where tomorrow's active pharmaceutical ingredients (APIs) are first described, recorded, and optimised.

The emergence of ELNs has highlighted the importance of workflow-specific, scalable chemistry handling available directly in the notebook. For instance, how an API is synthesised is often just as important as the chemical structure of the API, particularly as the substance moves through development. But some laboratory notebooks register only the separate components of a reaction, not the reaction process itself.

ELNs that do not capture transformations give you only part of the story – this is because a reaction is more than a collection of molecules – it also describes what changes during the reaction. When creating novel compounds, medicinal chemists and process developers need to locate potential transformations that can create desired entities. Such searches are only possible when actual transformations are captured and searchable in a database.

Symyx Notebook enables scientists to register and store full reaction schemes. More importantly, it enables chemists to rapidly search and retrieve information on individual molecules or full reaction schemes. Designed to power DiscoveryGate, Symyx's Internet-based collection of more than 17 million reactions and 30 million structures - Symyx Direct offers the ability to handle and effectively provide information on an organisation's proprietary research.

Because the chemistry used in Symyx Notebook is the same as that used in other Symyx systems, complementary software such as DiscoveryGate, Symyx Registration, and Symyx Isentris decision-support system can be readily integrated with Symyx Notebook to create a complete, seamless workflow. Full integration between Symyx Notebook and in-house and public data repositories minimises representation errors and enables more flexible and useful querying and information retrieval. It also enables scientists to conduct extensive searches over both in-house repositories (including data reported in Symyx Notebook) and public databases.

Content can also be provided in context when and where scientists need it. For instance, the Symyx Notebook materials table can be configured to automatically obtain properties and sourcing information from the Symyx Available Chemicals Directory (Figure 2). This enables scientists planning syntheses to act on property data automatically populated in tables through stoichiometry calculations and to assess immediately which materials are available from what vendors (Figure 3).

Fully integrated, world-class chemistry empowers scientists involved at every stage of the discovery and development workflow. It simplifies the description and registration of reactions, assists in reaction planning and methods development, and ensures that scientists at the bench, the analytical chemistry lab, or the plant have rapid and complete access to all the information available on APIs.

Symyx Notebook's chemical intelligence enables scientists to easily design and share single- and multistep, linear, and convergent reactions - and register all of the components and details of the transformation automatically to a corporate database.