A 2D chemical structure editor is a key component in most cheminformatics systems. With an ever-increasing number of groups using the Web as a cheminformatics platform, the need for a structure editor built specifically around the capabilities and constraints of the Web becomes more apparent.

For the last several months, my company (Metamolecular, LLC) has been developing a 2D structure editor called ChemWriter(TM). It was created specifically to solve the problem of building interactive, chemically-enabled Web applications that look good and load fast.

You can now download a free, fully-functional, non-expiring copy of ChemWriter (the ChemWriter Starter Package) good for development and testing of your chemically-aware Web application. The Metamolecular Company Blog has the details.

Of all the components that make up today's cheminformatics systems, the 2D structure editor may be the most widely-used. A 2D structure editor is often a chemist's first and most enduring exposure to cheminformatics, and can be encountered as early as Junior High or High School.

Over time, a good 2D structure editor becomes every bit as important to a chemist as a text editor is to a writer or software developer. At any given ACS organic division symposium, you're likely to find several bench chemists who only casually, if ever, use a 3D molecular modelling program; finding any who don't regularly use a 2D structure editor would be much more challenging.

2D structure editors are ubiquitous. They can be found in one form or another in most cheminformatics systems, ranging from databases, to standalone applications, to property calculators, and even 3D molecular modelling programs.

Despite the importance of structure editors, they don't get much attention among cheminformatics developers. For example, if your bibliography is anything like mine, it contains dozens of papers on molecular descriptors. Yet the number of cheminformatics papers describing the design of ergonomic chemical structure editors is, well, one or maybe two.

About ChemWriter

ChemWriter™ is a new product aimed at making 2D chemical structure editors a lot more interesting, easy to use, and versatile than they have been in the past. Designed specifically as a lightweight, extendable component, ChemWriter is ideal for use in chemically-enabled Web applications.

The second beta version of ChemWriter has recently been released by my company, Metamolecular, LLC. A recent article on the Metamolecular company blog discusses ChemWriter in more detail.

The Structure Editor In-Depth

Because the design and use of 2D chemical structure editors is an unusual subject in cheminformatics, a compilation of articles on the topic from Depth-First and the Metamolecular Web site is provided below. Many of these articles refer to "Firefly", which was ChemWriter's name during early development.

Why the Structure Editor Matters

• The Structure Editor: (Forgotten) Link Between Chemistry and Cheminformatics Title says it all.

• Four Free 2-D Structure Editors for Web Applications An early look with example code.

• Waldorf Salad Why aesthetics matter in chemistry.

Creating ChemWriter

• A 2D Chemical Structure Editor for the Web: Embracing Constraints in Firefly Creating remarkable products depends on identifying and embracing constraints.

• A Chemical Structure Editor for the Web: Four Screenshots of a Firefly Prototype Some screenshots of an early ChemWriter prototype.

• A Chemical Structure Editor for the Web: Firefly's Two Audiences A good structure editor needs to delight both developers and end users.

Using ChemWriter

• Open Notebook Science Using InChIMatic ChemWriter in action.

• Googling for Molecules with InChIMatic and Firefly One application of InChI using ChemWriter.

• Top Ten Best-Selling Drugs Worldwide (2006) - Depth-First Structures courtesy of an early development version of ChemWriter Desktop.

• Top Ten Best-Selling Drugs Worldwide With Structures 2006 - Metamolecular ChemWriter can also be used to dynamically render resizable 2D chemical structures in Web pages.

• ChemWriter and the Java Deployment Toolkit A simplified method for cross-browser applet deployment using ChemWriter.

• Transferring Molecules With ChemWriter Demonstrates how JavaScript can be used to move molecular information into and out of ChemWriter.

Extending ChemWriter

• Building a Molecule Preview with Firefly: The Joy of Swing Shows one use for ChemWriter as a Swing GUI component.

• Making Your 2D Structures Look Good: Firefly, Styles and Stylesheets Every aspect of ChemWriter's rendering can be customized, as is shown with this early development version of ChemWriter Desktop.

• Never Draw the Same Molecule Twice: Viewing Image Metadata Embedding 2D structure information as a molfile in PNG images.

• Editable and Searchable 2D Molecular Images Metadata applied in a novel way using a development version of ChemWriter Desktop.

A series of D-F articles have discussed InChIMatic, a Web application that lets you structure-search the Web using popular search engines such as Google. Recent articles have also described Firefly, a lightweight 2D structure editor designed especially for the Web.

Today, the first alpha release of Firefly is available for use with InChIMatic.

Despite its small size of only 103K, the Firefly applet offers a number of advanced features:

• A clean interface with major functionality in plain sight.

• Antialiased rendering. Pressing the "+" and "-" keys will zoom in and out to reveal rendering detail.

• User-overridable bond length and angle constraints. When dragging a bond, use Shift to relax both angle and length constraints, or Ctrl to relax only angle constraints.

• Automatic inside-outside double bond rendering.

• Built-in molfile import/export. Use the File->Import Molfile and File->Export Molfile options to copy/paste a molfile from your system clipboard.

• Automatic implicit hydrogen detection. The quadrant for hydrogen placement is chosen based on the bonds surrounding the atom.

• Twenty levels of undo/redo. The commands can either be issued from the menu, or Ctrl-Z/Ctrl-Y.

• Persistent molecule. When you visit another page and come back, Firefly remembers the molecule you were working on.

• No digital certificate authorization. Just start using it.

Firefly also incorporates a number of keyboard shortcuts to speed up structure drawing:

• 1-9 keys Builds a chain with the indicated number of carbons.

• a key Phenyl (aromatic) ring. When hovering over a bond, fuses the ring to the bond. When hovering over an atom, fuses the ring to that atom, if possible, or sprouts the ring.

• f, l, r, i keys The elements F, Cl, Br, and I, respectively.

• z and t keys The elements Si and Sn, respectively

• b, c, n, o, s, and p keys The elements B, C, N, O, S, and P, respectively.

• [delete] and [backspace] keys deletes whatever is underneath the cursor.

To use these shortcuts, simply hover the cursor over an atom and press the key on your keyboard.

Being an alpha release, this version of Firefly still has room for improvement. Your feedback is important. Please send questions, comments, and suggestions to the email address found under Firefly's "Help" menu.

Chemists can be very discerning when it comes to chemical structure aesthetics. This is not surprising, given the central role played by 2D chemical structures in the day-to-day work of many chemists. For example, consider the Wikipedia Chemistry/Structure drawing workgroup's ongoing discussion about achieving a consistent look for chemical structures on the online encyclopedia.

Several articles have discussed Firefly, a 2D chemical structure editor specifically designed for the Web. With major work on the rendering engine and structure manipulation interface complete, recent efforts have turned toward exposing drawing settings through a graphical user interface. Here I'll provide some screenshots of an interface prototype along with sample structures. I'll also briefly discuss the larger question of making 2D structure drawing styles portable.

Drawing styles are edited through a tabbed dialog containing a live preview window that uses the current structure or a default structure if none is available. The dialog is resizable, enabling users to immediately see the effects of changes on structures of varying sizes. Although this dialog could be bundled and deployed with the editor, its large footprint makes it more appropriate for use as an optional feature or as a standalone configuration tool in a Web application.

Changes can be rolled back entirely ("Reset"), canceled ("Cancel"), or accepted ("OK").

Let's say we'd like to apply a black background with white bonds, as used in some Power Point presentations:

  

After applying this change, we decide that we'd rather not use atom coloring:

  

After looking at this structure for a few seconds, we decide that narrower stereo bonds are needed:

  

After some experimentation, we find a more appropriate non-stereo bond width and double bond offset:

  

What about a Serif font? No, I don't think so:

  

But we could certainly reduce the size of the atom labels:

  

On second thought, the original atom sizes were fine, although changing font may require us to reconsider the atom label heights:

  

As you can see, the possibilities for customization are nearly endless. In practice, however, most chemists will adopt only two structure drawing styles that they re-use as needed: one for reports and manuscripts; and one for presentations. It will be interesting to see whether a third style makes it's way into the standard repertoire: Web.

Each chemist will want a way to save their styles, possibly share them, and easily apply them. Although a few systems for doing so are feasible, the most practical approach would be a stylesheet. Applying a stylesheet to any structure diagram would change its appearance, offering a simple mechanism to achieve a consistent look across documents.

Developing a universal (cross-editor) stylesheet system would be no easy task, given the wildly divergent capabilities of 2D structure rendering software. Despite the technical difficulty, the payoff for users is obvious.

The previous article in this series discussed the requirements of Firefly, a new 2D chemical structure editor for the Web. Another article discussed Firefly's design constraints and the importance of embracing them. Why so much focus on a structure editor? Simply put, the structure editor is the key link between chemistry and cheminformatics. Without the structure editor, there would be no audience for cheminformatics software.

So far the discussion has been rather abstract. To make it less so, the following four screenshots illustrate the user interface and rendering capabilities of a Firefly prototype. All molecules were drawn with the Firefly interface running on Linux. Screenshots were directly captured from the running application.

Cholesterol

The image below illustrates fused rings and stereo atoms. Also notice that the atom label for oxygen has one implicit hydrogen atom that is properly placed to the left.

Doxorubicin

This image illustrates both atom labels and aromatic bonding. Notice the improperly-placed quinone double bond. Refining Firefly's aromaticity perception is currently a top priority.

Flunoxaprofen

Firefly comes complete with a developer-overridable atom coloring scheme. Also notice the correct length of the internal carbon-nitrogen double bond line.

Uric Acid

One of the more difficult aspects of rendering molecules with implicit hydrogens is placing them in the correct quandrant. In this screenshot of uric acid, notice how the hydrogens occupy three different quadrants relative to their hosting nitrogen atoms.