Automatic identification of relevant chemical compounds from patents.

In commercial research and development projects, public disclosure of new chemical compounds often takes place in patents. Only a small proportion of these compounds are published in journals, usually a few years after the patent. Patent authorities make available the patents but do not provide systematic continuous chemical annotations. Content databases such as Elsevier's Reaxys provide such services mostly based on manual excerptions, which are time-consuming and costly. Automatic text-mining approaches help overcome some of the limitations of the manual process. Different text-mining approaches exist to extract chemical entities from patents. The majority of them have been developed using sub-sections of patent documents and focus on mentions of compounds. Less attention has been given to relevancy of a compound in a patent. Relevancy of a compound to a patent is based on the patent's context. A relevant compound plays a major role within a patent. Identification of relevant compounds reduces the size of the extracted data and improves the usefulness of patent resources (e.g. supports identifying the main compounds). Annotators of databases like Reaxys only annotate relevant compounds. In this study, we design an automated system that extracts chemical entities from patents and classifies their relevance. The gold-standard set contained 18 789 chemical entity annotations. Of these, 10% were relevant compounds, 88% were irrelevant and 2% were equivocal. Our compound recognition system was based on proprietary tools. The performance (F-score) of the system on compound recognition was 84% on the development set and 86% on the test set. The relevancy classification system had an F-score of 86% on the development set and 82% on the test set. Our system can extract chemical compounds from patents and classify their relevance with high performance. This enables the extension of the Reaxys database by means of automation.

Photorelease of alcohols from 2-nitrobenzyl ethers proceeds via hemiacetals and may be further retarded by buffers intercepting the primary aci-nitro intermediates.

The mechanism for the photoinduced release of glycolic acid from its 2-nitrobenzyl ether was reinvestigated. The pH-dependent rate constants of the thermal reactions initiated by irradiation are similar to those reported previously for 2-nitrobenzyl methyl ether. A hemiacetal intermediate that limits the release rate of glycolic acid at pH values

Photochemical reaction mechanisms of 2-nitrobenzyl compounds: 2-nitrobenzyl alcohols form 2-nitroso hydrates by dual proton transfer.

Irradiation of 2-nitrobenzyl alcohol (1, R = H) and 1-(2-nitrophenyl)ethanol (1, R = Me) in various solvents yields 2-nitroso benzaldehyde (4, R = H) and 2-nitroso acetophenone (4 R = Me), respectively, with quantum yields of about 60%. The mechanism of this reaction, known since 1918, was investigated using laser flash photolysis, time-resolved infrared spectroscopy (TRIR), and 18O-labeling experiments. The primary aci-nitro photoproducts 2 react by two competing paths. The balance between the two depends on the reaction medium. Reaction via hydrated nitroso compounds 3 formed by proton transfer prevails in aprotic solvents and in aqueous acid and base. In water, pH 3-8, the classical mechanism of cyclization to benzisoxazolidine intermediates 5, followed by ring opening to carbonyl hydrates 6, predominates. The transient intermediates 3 and 6 were identified by TRIR. Potential energy surfaces for these reactions were mapped by density functional calculations.

Photochemical reaction mechanisms of 2-nitrobenzyl compounds: methyl ethers and caged ATP.

The mechanism of methanol photorelease from 2-nitrobenzyl methyl ether (1) and 1-(2-nitrophenyl)ethyl methyl ether (2), and of ATP release from adenosine-5'-triphosphate-[P(3)-(1-(2-nitrophenyl)ethyl)] ester ('caged ATP', 3) was studied in various solvents by laser flash photolysis with UV-vis and IR detection. In addition to the well-known primary aci-nitro transients (A, lambda(max) approximately 400 nm), two further intermediates preceding the release of methanol, namely the corresponding 1,3-dihydrobenz[c]isoxazol-1-ol derivatives (B) and 2-nitrosobenzyl hemiacetals (C), were identified. The dependencies of the reaction rates of A-C on pH and buffer concentrations in aqueous solution were studied in detail. Substantial revision of previously proposed reaction mechanisms for substrate release from 2-nitrobenzyl protecting groups is required: (a) A novel reaction pathway of the aci-tautomers A prevailing in buffered aqueous solutions, e.g., phosphate buffer with pH 7, was found. (b) The cyclic intermediates B were identified for the first time as the products formed by the decay of the aci-tautomers A in solution. A recently proposed reaction pathway bypassing intermediates B (Corrie et al. J. Am. Chem. Soc., 2003, 125, 8546-8554) is shown not to be operative. (c) Hemiacetals C limit the release rate of both 1 (pH < 8) and 2 (pH < 10). This observation is in contrast to a recent claim for related 2-nitrobenzyl methyl ethers (Corrie et al.). Our findings are important for potential applications of the 2-nitrobenzyl protecting group in the determination of physiological response times to bioagents ('caged compounds').