Chemical structure databases have the odd distinction of being both ubiquitous and often non-trivial to implement. The defining characteristic of these systems is that records can be fetched based on exact- or substructure queries. Structure-searchable databases pops up in all kinds of contexts ranging from individual research projects to on-off data processing tasks to drug discovery efforts to analytical labs to small chemical businesses.

As the joke goes, the difference between computational chemistry and cheminformatics is that in computational chemistry molecules get to keep their hydrogens. The two fields clearly start from different assumptions, using them to answer different kinds of questions. One of the more striking differences between the two fields is the treatment of aromaticity.

SMILES is a de facto standard for chemical structure representation. The core language can be picked up quickly, but just below the surface lie some surprisingly complex concepts. One of the most difficult of these is “aromaticity.” A previous article described a comprehensive approach to reading aromatic SMILES. The following article details a method for writing aromatic SMILES.

Molecular representation underpins all of cheminformatics and, arguably, chemistry itself. Getting molecular representation right is hard because it supports so many applications, and because all forms of molecular representation have limitations. When a molecular representation system finds its way into applications for which it’s underqualified, the result can range from annoying to catastrophic.

How can life be recognized as such? The question has great scientific, technological, and cultural importance. One school of thought says that we should start with a definition. But after 123 attempts and counting, just defining the word “life” has yielded more heat than light.

InChI is an IUPAC-sponsored project aimed at creating a distributed chemical identifier system. Centralized identifiers like CAS Registry Numbers operate through intermediaries who curate entries, resolve conflicts, and often charge a substantial fee for the service. InChI is different in that identifiers are generated deterministically through software, independent of an intermediary.

Cheminformatics and chemistry don’t always move in tandem. A case in point is multi-atom bonding. Organometallic species, which have been made, characterized, and used for decades serve as the most obvious example. But there are more subtle cases as well, such as tautomers and mesomers. These species all highlight the problems of building cheminformatics on the shaky ground of valence bond theory.

InChI is an IUPAC standard and software package for chemical identification. For most small organic molecules likely to be found in a drug discovery program, a stockroom, or a chemical database, the InChI software creates a unique character sequence. InChI is useful because it enables fast exact-structure lookup within a single database and among different databases.

Although it receives relatively little attention in cheminformatics, ChemDraw may be the most important piece of software in chemistry. Every chemist with experience beyond high school will probably have at least heard of it. ChemDraw is the de facto standard for creating graphics for publications and presentations, with every major journal providing settings for authors.

At the recent NIH Virtual Workshop on InChI, I gave a talk titled Running InChI Anywhere with WebAssembly . This article expands some of the major points and answers a couple of questions I got. WebAssembly is a Big Deal Although it’s flown under the radar for years, WebAssembly (aka Wasm) is a big deal.

InChI and SMILES stand as the two de facto standard line notations for cheminformatics. A line notation represents a molecular graph as a compact string of characters without newlines. Given its similarity to SMILES, a reasonable assumption would be that InChI can be parsed to regenerate the molecular graph that created it. With few exceptions, this is not the case. This article explains why.