Fig. 1. An overview of the Search ILToxDB form.
Molecular mass is selected as Criterion 1, and range 125..150 g/mol is specified.
Criterion 2 is being selected in a drop-down.
The interface of the Ionic Liquid Toxicity Database (ILToxDB) is minimalistic and user-friendly. The navigation bar at the top includes the following tabs:
Any entry in the ILToxDB corresponds to a cytotoxic activity (half-maximal cytotoxicity/inhibitory/effective concentration, or CC50/IC50/EC50) of a particular chemical compound studied in a given cell line by a given assay and reported in a particular research paper. For more details on the data deposited in the database, please refer to [ Arakelyan L.A. et al. “A comprehensive dataset on cytotoxicity of ionic liquids”, Scientific Data, 2024, 11:1379 ] (DOI: 10.1038/s41597-024-04190-3).
An overview of the Search ILToxDB form is shown in Fig. 1. Available search criteria are listed in a dropdown menu. Users can use up to eight criteria (including those of the same type), combined using boolean AND. The button on the right adds another the search criteria for multicriterion search; the button removes the last criterion. The whole ILToxDB content can be viewed by pressing the button to the right.
There are four groups of search criteria available: compound, assay, cell line, and publication. Compound criteria include compound name, CAS, cation category, structure, brutto formula, and molecular mass. The assay criteria characterize the method used for cytotoxicity tests. They include the ILToxDB entry IDs, type of assay used to measure the cytotoxicity, and CC50 (half-maximal cytotoxicity/inhibitory/effective concentration). The cell line criteria are related to the cells, in which the cytotoxicity is studied. They include the cell line, cell type, disease, tissue, organism, ATCC ID, and Cellosaurus ID. The publication criteria describe the publication(s), in which the cytotoxic effects are described. They include DOI, the first author, journal, and year of publication. More details on each criterion are given below.
This group of search criteria allows specifying the chemical attributes of the compounds being searched for. The following compound criteria are available:
To draw a structure, select the Structure criterion and press the button next to an input field (Fig. 2A). An online drawing tool (JMSE molecular editor published in [DOI: 10.1186/1758-2946-5-24]) will appear (Fig. 2B). Upon completing the drawing, press (Convert Structure to SMILES), and the corresponding SMILES code will be inserted into the query. Users can also input a SMILES string into the query field directly and click (Convert SMILES to Structure) to open an editor with the corresponding molecular structure displayed. This structure can be subsequently modified and converted back into a SMILES code.
When more than one row contain Structure search criterion, and buttons operate independently in each row, however the editor window is shared between them.
To draw a structure containing multiple entities, e.g. a cation and an anion, use NEW button in the JMSE toolbar to add another entity. Alternatively, you can use more than one (Sub)structure criteria: the search will return compounds containing all these structural fragments, including those having these fragments in different entities.
When resonance structures are possible, charge location is canonicalized upon search. However, please note that charged and neutral atoms are not the same, e.g. Cl query will not return [Na+][Cl-] but will return C(C)Cl, while [Cl-] query will return a salt but not a covalent chloride.
The assay criteria allow usage of ILToxDB identifiers or setting certain methodological limits to the search:
The cell line criteria describe the cells, in which the cytotoxicity was studied. The following characteristics can be queried:
The publication criteria define the original research paper(s), in which the cytotoxic effects were established. They include:
After the desired search criteria are specified, pressing the button starts the search. Fig. 3 shows the result of an exemplary search using 1-butyl* as a compound name. ILToxDB returned 103 entries matching this query (only three of them are shown for clarity).
The search results are displayed as a table containing four columns: Compound, Assay, Cell line, and Reference. Each row in the table corresponds to a database entry that meets the criteria specified in the search form. The results can be sorted by CAS, name (in Compound column), CC50, ID (in Assay column), organism, cell line (in Cell line column), year of publication, first author (in Reference column) by clicking on the corresponding black arrows in the table header.
The Compound cell includes chemical information on a given compound: its IUPAC name, CAS registry number (if available), molecular mass, structural formula and category, and specific data for IL mixtures. Clicking on the CAS number opens the corresponding entries (if available) in the PubChem database in a new tab. Clicking on the Show SMILES link displays the compound SMILES code for copypasing. Clicking on the structural formula opens it in an SVG format in a new tab. Currently, there is no search for mixtures, however, when any of the components match a regular search query, mixtures are returned among the other results and marked.
The Assay cell includes the actual cytotoxicity value (half-maximal cytotoxicity/inhibitory/effective concentration, or CC50/IC50/EC50, in mM); statistical dispersion (standard deviation (SD), standard error of the mean (SEM), 95% confidence interval (95% CI), etc., if available); incubation time; and assay used. Clicking on the assay name shows its brief description. A link Presumable mechanism (click for description) is present if experimental information on the cytotoxicity mechanism of a particular IL is provided in the publication. The ILToxDB ID of the entry is shown in the right bottom corner of the cell.
The cell background reflects the CC50/IC50/EC50 value in a logarithmical way from red (<0.001 mM) to green (>9 mM) via yellow.
The Cell line cell shows the cell line, in which the effect was tested (including other and synonymic names in parentheses); its ATCC and Cellosaurus identifiers; species and tissues, from which the cells were derived; disease, which the cell line corresponds to (if any); morphology of the cells (if available); and the cultural medium used in a particular study, with the manufacturer shown in parentheses (if available). Clicking on the ATCC or Cellosaurus identifiers opens the corresponding records in ATCC or Cellosaurus in a new tab. Clicking on the species name opens the corresponding record in the NCBI Taxonomy Browser.
The Reference cell contains the bibliographic data for the research paper, in which the effect was described: the first author, journal, year of publication, and DOI. Clicking on DOI opens the paper on the publisher’s web-site.
The results can be exported in TSV (tab-separated values) format or downloaded as a TSV file by clicking at the Export TSV link at the end of the table. This file can be opened for further processing in any spreadsheet editor, e.g. Microsoft Excel.