Chemdraw Fragmentation Tool
Lorin Mandaloniz
The Mass Fragmentation tool allows you to break existing structures across one or more bonds. This mimics the molecular fragmentation in a mass spectrometer, but does not have any predictive qualities: you must specify what bonds are to be broken.
When the line crosses a bond, the formula and exact mass for the fragments on either side of the bond are displayed as if the bond were homolytically broken. That is, a single bond turns into a monoradical on each fragment; a double bonds turns into a pair of diradicals. If more than one bond is crossed, all fragments on each side of the line are considered together. If the only bond crossed is a ring bond, a single formula/mass pair is displayed.
I am a results-oriented biochemist with over a decade of experience performing research and process development spanning microbiology, protein chemistry, and formulation development. My background includes extensive work in high-throughput assays, analytical chemistry, microbiology, project coordination, and lab management.
Have you ever wondered how to make professional, easy-to-understand figures of molecules for presentations or publications? While several programs exist for this purpose, ChemDraw is like the Swiss Army knife of chemical sketching programs that most chemists and journals use to prepare figures.
ChemDraw is quite intuitive for new users. If you understand skeletal formulas, you can use ChemDraw! The program includes a plethora of customizable options, like setting bond lengths and widths, changing the font and size of individual atoms, and changing the colors of atoms and bonds. You can include stereochemistry and rotate molecules in all axes. Molecular charges, atomic orbitals, and individual electrons are also included.
Speaking of mass spectrometry, the Mass Fragmentation tool shows the fragment molecular weights as you select possible fragmentation points. Simply drag the fragmenting tool over the bond you want to break to get exact masses of each fragment.
Newer versions of ChemDraw have a direct link to SciFinder, which is a powerful addition to this already versatile software. Simply select a structure or reaction and click the SciFinder button. From there, you can explore experimental properties, published literature and patents, and synthesis routes.
Through many trials, and lots of error, I learned that there are many considerations for mass spectrometry that might not be obvious to you as a molecular biologist. Common contaminants, even in small quantities, can mask important peaks in your mass spec data and have a huge impact on the final results.
To set up your ChemDraw to connect to SciFinder-n at U of T, select your structure and open up the search by going to Add-ins > Search SciFinder-n from the menu along the top of your screen. Before running your search, click Proxy Settings and enter the following link in the box that appears:
= -n.cas.org
Your ChemDraw software is now set up to connect to our SciFinder-n license at U of T! You will be asked to log in with your UTORid and password and enter your SciFinder-n credentials before proceeding to your search results in SciFinder.
ChemDraw is a downloadable application for drawing chemical structures for use in database queries, the preparation of graphics for lab reports and journal articles, providing electronic descriptions of molecules and reactions, and features advanced prediction tools.
Create tables of structures, identify and label stereochemistry, estimate NMR spectra from ChemDraw structures, obtain structures from chemical names, assign names from structures, and create multi-page documents and posters. There is rich polymer notation, generic structure expansion and fragmentation tools.
Developing and implementing computational algorithms for the extraction of specific substructures from molecular graphs (in silico molecule fragmentation) is an iterative process. It involves repeated sequences of implementing a rule set, applying it to relevant structural data, checking the results, and adjusting the rules. This requires a computational workflow with data import, fragmentation algorithm integration, and result visualisation. The described workflow is normally unavailable for a new algorithm and must be set up individually. This work presents an open Java rich client Graphical User Interface (GUI) application to support the development of new in silico molecule fragmentation algorithms and make them readily available upon release. The MORTAR (MOlecule fRagmenTAtion fRamework) application visualises fragmentation results of a set of molecules in various ways and provides basic analysis features. Fragmentation algorithms can be integrated and developed within MORTAR by using a specific wrapper class. In addition, fragmentation pipelines with any combination of the available fragmentation methods can be executed. Upon release, three fragmentation algorithms are already integrated: ErtlFunctionalGroupsFinder, Sugar Removal Utility, and Scaffold Generator. These algorithms, as well as all cheminformatics functionalities in MORTAR, are implemented based on the Chemistry Development Kit (CDK).
In quantum mechanics, molecular systems are holistic entities whose properties can only be fully understood by studying their complete structures. However, a reductionist approach that considers a molecular structure as a sum of multiple substructures has proven useful. A prominent example is the concept of functional groups (FG), which allows an assessment of molecular reactivity or toxicity based on specific FG occurrence. The concept is important for nomenclature generation, spectroscopy, combinatorial chemistry, or drug development as well [1].
Fragmentation algorithms like the ones mentioned above can be seen as distillates from chemical expert knowledge that allow computer programs to identify characteristic molecular substructures in a comprehensible way based on structural definitions for functional concepts like functional groups. Their advantage over methods employing pre-defined lists of substructure patterns is that they are complete, i.e., they capture the true diversity of substructures like functional groups, scaffolds, or glycosidic moieties. These traits make them important for fields like drug design, CASE, or NP research.
The development of fragmentation algorithms is often an iterative process with multiple steps of defining a rule set, applying it to suitable structural data, inspecting the results, and refining the algorithm based on what was observed in the previous step. This requires a testing workflow with fragment visualisation functions where two perspectives are of interest: One based on an individual molecule, i.e., which fragments result from its structure. The other considers a complete data set, asking which fragments occur how often in a set of structures. When a new fragmentation algorithm is ready for publication, it is usually released to the scientific community as a stand-alone command-line tool or as part of a cheminformatics programming library. If users want to visually inspect the fragment set generated by the new algorithm for their own set of molecules, they have to implement corresponding workflows themselves.
This work presents an open Java rich client Graphical User Interface (GUI) application, abbreviated MORTAR (MOlecule fRagmenTAtion fRamework), with the intention to support the development of new in silico molecule fragmentation algorithms as well as enable their later distribution in a more accessible way. Its main functionalities are importing molecule sets from various file formats, applying fragmentation algorithms, and visualising the results in a graphical display that alleviates the investigation of the resulting fragment sets and the fragmentation results of individual molecules. Using MORTAR, no programming skills are needed to perform these steps, which makes conducting in silico fragmentation studies more accessible. MORTAR can be installed and used on three major operating systems (Windows, macOS, and Linux) and uses parallel computing on multi-core processors for CPU-intensive processes. To our knowledge, there is currently no comparable open software application available. For cheminformatics functionalities, the Chemistry Development Kit (CDK) [32,33,34] is employed internally. Fragmentation algorithms can be integrated into or directly developed in MORTAR straightforwardly. Upon release, three algorithms are available: The Ertl algorithm for functional group identification via its open implementation ErtlFunctionalGroupsFinder [35], the Sugar Removal Utility for glycosidic moiety detection and removal, and Scaffold Generator [36], a software library for scaffold functionalities, including the scaffold tree dissection into parent scaffolds and an enumerative parent scaffold generation routine for scaffold networks. More functionalities will be added in future releases and with MORTAR being open-source, the software itself can be enhanced or tailored to individual needs.
MORTAR was implemented as a rich client application based on Java 17 using Adoptium OpenJDK [37]. Gradle [38] was used to facilitate the build process and the integration of further libraries. All libraries used are obtained from the Maven Central Repository [39].
The architecture of MORTAR follows a Model-View-Controller (MVC) pattern based on the object-oriented Java framework. MORTAR is available on GitHub as a free open-source project: The repository contains the complete source code, an extensive graphical tutorial explaining every detail of the GUI, and an installation guide.
The class structure is organised according to the MVC pattern with one package for each layer. The view classes are designed with JavaFX [40] and located in their respective sub-packages of the gui package: controls, util, and views. These classes are governed by a layer of controller classes which are located in the controller package. The controllers pass on the user input to a layer of model classes and update the GUI according to the resulting changes in the data model.
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