Our chapter provides some fairly detailed examples of how Open Notebook Science can be used to enhance collaboration between researchers from both similar or distant fields. It also suggests certain paths towards machine/human collaboration in science. Hopefully it will encourage researchers who have an interest in Open Science to experiment with some of the tools and strategies mentioned.
I am also grateful to Wiley for choosing our chapter as the free online sample for the book!
This book discusses the state-of-the-art collaborative and computing techniques for the pharmaceutical industry, the present and future implications and opportunities to advance healthcare research. The book tackles problems thoroughly, from both the human collaborative and the data and informatics side, and is very relevant to the day-to-day activities running a laboratory or a collaborative R&D project. It can be applied to help organizations make critical decisions about managing drug discovery and development partnership. The book follows a “man- methods-machine” format with sections on how to get people to collaborate, collaborative methods, and computational tools for collaboration. This book offers the reader a “getting started guide” or instruction on “how to collaborate” for new laboratories, new companies, and new partnerships, as well as a user manual for how to troubleshoot existing collaborations.
I am pleased to report that Andrew Lang and I have published the first edition of the Reaction Attempts book. It currently contains most of the Ugi reactions from the UsefulChem project and is associated with an April 27, 2010 snapshot archive of the entire UsefulChem project, including NMR spectra, spreadsheets, images and the entire lab notebook from Wikispaces.
At 582 pages the printing cost from LuLu amounts to $26.28. Not meant to replace electronic searches, it should prove to be a handy reference book for the lab to quickly browse through what was attempted for a given reactant, what the outcome was and the researcher involved.
We are hoping to include reaction attempts from other groups in future editions. More details can be found in the preface, reproduced below:
Reaction Attempts First Edition
Data Source: the UsefulChem project
Introduction
Open Notebook Science (ONS) refers to the practice of making the full contents of a laboratory notebook and all associated raw data files available in near real time.[1] This represents an opportunity for everyone to benefit from work in progress in an open research group. However, in order to make use of the information, it must be easily discoverable. A simple strategy to increase discoverability is redundancy over multiple communication platforms.
In another project - the Open Notebook Science Solubility Challenge[2] - we published non-aqueous solubility data in the form of physical and downloadable (PDF) books.[3] Although it is possible to search the solubility database using web query interfaces, exploration of a Google Spreadsheet, an XML feed, etc.[4], having a physical copy in the laboratory has proved to be very convenient in several instances. A similar format for reactions will also be useful.
The UsefulChem Project
UsefulChem started in 2005 as an organic chemistry Open Notebook Science project with a main goal of discovering new anti-malarial agents that can be prepared by simple and cheap syntheses.[5] Most of the reactions on UsefuChem are Ugi reactions, which involve the mixing of an amine, aldehyde, carboxylic acid and isonitrile in a solvent at room temperature generally for a few hours to days.[6] The multicomponent design of the Ugi reaction and the simple reaction conditions make it ideal for exploring large virtual libraries and selecting compounds of interest to make.[7]
Isolation of the Ugi products can be immensely simpler, cheaper and readily scalable if they precipitate in pure form from the reaction mixture. To this end, much of the research in the UsefulChem project focuses on reaction conditions that lead to this outcome.[8] This is in fact the origin of the ONS Solubility Challenge discussed above.[9]
The Reaction Attempts Database
In order to look for patterns in the reaction conditions which led to Ugi product precipitation, the CombiUgiResults Google Spreadsheet was set up.[10] Reactions indexed there can be sorted by precipitation outcome, solvent, reactant, concentration, etc. and links to the laboratory notebook pages can be followed for full details. However, this sheet is designed specifically for Ugi reactions and contains columns specifically for the aldehyde, amine, carboxylic acid and isonitrile.
In order to enable the tracking of other types of reactions, the information in the CombiUgiResults sheet was reformatted into two other sheets: ReactionAttempts[11] (containing reagents and reactants) and RXIDsReactionAttempts[12] (containing reaction conditions and results, such as solvent, concentration of limiting reactant, appearance of a precipitate, yield, etc.). The two sheets are connected via the use of a common ReactionID. This format permits the representation of any type of reaction, with an unlimited number of reactants and products.[13]
By definition, any Open Notebook Science project in a work in progress. The listing of a reaction in this database only means that the researcher attempted or is in the process of attempting it. Whatever the situation, a link to the laboratory notebook page is provided, where the most recent information is available. The philosophy used here is that partial information is always better than no information at all. Thus a researcher investigating the prior use a particular reactant in a Ugi reaction might find the report that a precipitate was obtained in methanol helpful for designing their own reactions, even if the characterization of the precipitate is still pending. At the very least, knowing that a certain researcher has at least attempted a similar reaction is enough information for initiating a discussion, which may lead to valuable insights.
Reaction Attempts on Chemspider
Although SMILES[14] are provided in the spreadsheets, the primary key to identify compounds is the ChemSpider ID (CSID)[15]. This allows us to render molecule images in the book automatically. In the case of the ONS Solubility Challenge book[3], use of the CSID enables a convenient way to calculate various descriptors for displaying values in the book.
In addition, the compounds in the Reaction Attempts database are indexed on ChemSpider as two Data Sources: ReactantsAttemptedReactions and ProductsAttemptedReactions[13]. In this way a substructure search for either reactants or products will identify indexed molecules. Clicking on the Syntheses tab in the ChemSpider record for a selected molecule will then reveal a list of hyperlinks to the relevant laboratory notebook pages.
Organization of the Book
In keeping with the layout of the ONS Solubility Challenge Book, the reactants are listed in alphabetical order. Each entry displays the list of reactions where the reactant was used. This includes a scheme with all reactants and product as well as key metadata: the researcher, reaction type, solvent, limiting reactant concentration, observation of a precipitate, comments and a reference (links to the laboratory notebook page).
In this edition, only Ugi reactions are included. The reaction schemes are laid out in the following order: carboxylic acid, amine, aldehyde and isonitrile. This should allow for easy comparison between schemes within a given record. Reactions where the Ugi product was isolated and characterized are marked with a green check and the percent yield is noted. Since the Ugi products do not have simple common names, they are not included as separate entries. However, all reactions where the synthesis of a specific Ugi product was attempted can be found by looking up the entries for any of the four reactants.
Although this compilation is not exhaustive, it does cover the vast majority of reactions in the UsefulChem project to date. Future editions will include other reactions from UsefulChem and other sources.
Archive
This edition is linked to the UsefulChem data archive (ZIP)[16], (DVD)[17] and interactive hosted archive format[18], ReactionAttempts (XLS)[19] and RXIDsReactionAttempts(XLS)[20] taken on 2010-04-27.
We've been trying for some time to find a way to conveniently take a snapshot of our Open Notebooks and all associated raw data files. This could serve as a way to back up all of our work as well as provide a means of finding out the state of knowledge for a project at a given moment in time. There is also a tremendous benefit to confidently using the best of free hosted Web2.0 services out there (e.g. GoogleDocs and Wikispaces) without being concerned with changes in policies or access down the road.
Our recent use of the ONS Challenge Solubility book to periodically create releases of summarized data has opened up a convenient opportunity. And yesterday the last piece of the puzzle fell into place. Through a combination of fairly quick manual and automated tasks, Andrew Lang and I are able to push out a full snapshot of all relevant files and lab notebook pages and associate it with an edition of the book.
As described below, the archive is accessible interactively on a server, as a zip download or as a CD from LuLu. Perhaps we can also find a home on library servers in the future.
This is the first edition to include a full archive of the ONS Challenge notebook. A space export from Wikispaces provides an initial version of all the HTML pages in the notebook with local hyperlinks to copies of all images and files uploaded onto the wiki. All of the Google Spreadsheets are automatically downloaded as Excel spreadsheets and placed in the same "files" folder as the images. NMR spectra, stored as JCAMP-DX files, are placed in the "spectra" folder. All of the HTML pages are reformatted to provide local references to both Excel spreadsheets and the JCAMP-DX files.
The notebook archive is meant to represent a snapshot of the state of all source documents at the time of the publication of an edition of this book. When used from a server with web services running, clicking on links to the spectra will allow interaction via a browser interface, including zooming in or out and integration of the NMR spectrum. When accessed in stand-alone mode after downloading or directly from a CD, everything will work the same, except that JCAMP-DX files must be open from JSpecView running on the desktop. Excel files will retain any calculations in the cells of the original Google Spreadsheets but dynamic values generated from calling web services - such the script that automatically integrates NMR spectra - will be frozen as simple values. However the link to the web service used will be stored in the cell as a comment. Links to external websites are not crawled and embedded Google Spreadsheets or videos are not copied. These will work but will reflect live data on the web.
The February 11, 2010 version of the notebook archive is available on a hosted site, on a CD or by download.
However, the main difference is the addition of a new section on solubility predictions. The book is now somewhat larger than the first edition, coming in at 129 pages but still very affordable at $8.16 (covers printing and shipping costs from LuLu).
This was added to the preface:
Predicted Solubilities
In this edition, a new section is added to provide predicted solubility values for selected solutes in a range of solvents. Specifically, solutes are included when measurements from at least 5 different solvents are available. A method using Abraham descriptors depends on the experimental solubility measurements from several solvents to make predictions, which is detailed in that section of the book. For this reason, this edition also includes some aqueous solubility measurements, which are generally available from the literature. The focus of this collection remains on non-aqueous solubility.
Consistent with how the experimental measurements are made available, the predicted solubility values are provided as a work in progress. The purpose in providing them is to suggest solvents of interest for various applications. The boiling point of each solvent is also listed in the table to allow a convenient selection. When available, experimental measurements are listed next to the predicted values. This information can be helpful to gauge the usefulness of the model to some extent but does not guarantee its reliability for the other solvents. As more measurements are collected the reliability of the predictions is likely to increase and this will be reflected in future editions of this book.
Abraham M.H.; Smith R.E.; Luchtefeld R.; Boorem A.J.; Luo R.; Acree Jr. W.E. Prediction of solubility of drugs and other compounds in organic solvents.J. Pharm. Sci. Early View Sept. 22 (2009) http://dx.doi.org/10.1002/jps.21922
This is an important step for the ONS Challenge project by taking us closer to the eventual goal of providing chemists an open tool for anticipating the solubility behavior of their reactants and products in a particular solvent. Researchers might think of trying new solvents after perusing their measured or predicted solubilization potential for a given solute.
We don't know how good the predictions will turn out but we will certainly find out in the coming months and report as we go. Even though the Submeta awards have all been distributed we still welcome measurement contributions.
