Blind trials of computer-assisted structure elucidation software

Abstract

BackgroundOne of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an in silico structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments.ResultsBeginning in 2003, and for the following nine years, the algorithms and software technology contained within ACD/Structure Elucidator have been tested against 112 data sets; many of these were unique challenges. Of these challenges 9% were double-blind trials. The results of eighteen of the single-blind trials were investigated in detail and included problems of a diverse nature with many of the specific challenges associated with algorithmic structure elucidation such as deficiency in protons, structure symmetry, a large number of heteroatoms and poor quality spectral data.ConclusionWhen applied to a complex set of blind trials, ACD/Structure Elucidator was shown to be a very useful tool in advancing the computer's contribution to elucidating a candidate structure from a set of spectral data (NMR and MS) for an unknown. The synergistic interaction between humans and computers can be highly beneficial in terms of less biased approaches to elucidation as well as dramatic improvements in speed and throughput. In those cases where multiple candidate structures exist, ACD/Structure Elucidator is equipped to validate the correct structure and eliminate inconsistent candidates. Full elucidation can generally be performed in less than two hours; this includes the average spectral data processing time and data input.

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

“…Computer‐assisted structure elucidation (CASE) is a computational approach to analyze the analytical data and suggest hypothetical structures consistent with it . The capabilities and performance of the ACD/Structure Elucidator software suite have been reported previously . The process can be summarized as utilizing the available NMR chemical shift and correlation data together with the molecular formula to assemble molecular structures consistent with that data.…”

“…[17] The capabilities and performance of the ACD/Structure Elucidator software suite [18] have been reported previously. [19,20] The process can be summarized as utilizing the available NMR chemical shift and correlation data together with the molecular formula to assemble molecular structures consistent with that data. While many tens of thousands of structures may be assembled from the data, rank-orderingo ft he structures using NMR prediction algorithms [21] compares experimental chemical shifts to predicted shifts to identify the most likely candidate(s).…”

EBC‐232 and 323: A Structural Conundrum Necessitating Unification of Five In Silico Prediction and Elucidation Methods**

“…At this point in the elucidation process, ACDLabs NMR Structure Elucidator (version1 0.01) [7] platform was consulted. [20] Raw NMR data, [21] along with the molecular formula, werei nputted.…”

Reassignments and Corroborations of Oxo‐Bridged Natural Products Directed by OSE and DU8+ NMR Computation

“…Considering the extensive time and spectroscopic demands (e.g., NMR, IR, UV‐vis, MS, CD) involved in correctly elucidating a novel natural product, the prevalence of misassignments in the literature is perhaps understandable . There are now numerous in silico methods to help with structure elucidation by predicting spectra (e.g., NMR, ECD) from chemical structure input or conversely by predicting chemical structure from spectroscopic data (e.g., ACDLabs). Yet in spite of these new technologies, misassignments continue to appear.…”