Expert systems biodegradation

In a molecule, smaller bond angles are formed between electronegative ligands since the central atom, to which the ligands are attached, tends to direct bonding hybrid orbitals of greater p character toward its more electronegative substituents. 

A database referencing chemical literature. See Chemical Abstracts Service Information System. 

Biodegradation is one of the major processes by which chemicals disposed in dump sites, sewers, lakes, rivers, and other environmental sites can be degraded into innocuous products such as carbon dioxide and water that are readily assimilated into the environment. If a chemical is not mineralized or broken down to nontoxic products in the environment, it can impact the ecosystem at several points, causing health, economic, and aesthetic problems. Toxic chemicals, if not degraded may persist in the environment and create health hazards to humans and animals. 

Environmental groups and the chemical industry are greatly concerned about disposal of man-made chemicals, particularly if they are suspected of possessing deleterious properties. The use of such chemicals as herbicides, pesticides, pharmaceuticals, polymers, detergents and so on, increases steadily in 

Biodegradation results from ground and water metabolism by environmental microorganisms. These microorganisms will feed on disposed materials, sometimes after acclimation and transform them into smaller biodegradation products. In the best cases, biodegradation results in the transformation of synthetic chemicals into innocuous compounds. In the worst cases, an innocuous parent chemical could be transformed into a stable but toxic metabolic product. 

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Biodegradation Expert Systems Comparative Molecular Field Analysis (CoMFA) Environmental Information... 

The META system (291-293) is an expert system, based on well-established sources, for predicting the sites of potential enzymatic attack and the metabolites formed by metabolic transformations. The program uses dictionaries of biotransformation operators, which are created by experts to represent known metabolic paths. Currently, META can be combined with one of the following dictionaries mammalian metabolism, aerobic biodegradation, anaerobic biodegradation, and metabolic transformation reactions (291). 

In summary, optimization of the environmental profile of APIs starts from a new or already known lead structure. During the pharmaceutical optimization process, which involves systematic variation of parts of the molecule, the biodegradability of the resulting structures is also monitored. Candidates that possess both better pharmaceutical and environmental properties advance to the next round of optimization. With the help of modem in silico methods (e.g., QSARs, expert systems) this can be done systematically, quickly, and cheaply, without the need to synthesize all the molecules of interest [132]. In a similar way, we were able to improve the biodegradability of a new lead structure by systematically modifying the lead molecule while retaining the necessary low octanol-water partition coefficient. As... 

Current generally applicable biodegradation models focus on the estimation of readily and nonreadily biodegradability in screening tests. This is because most experimental data are from such tests (e.g., MITI-I). There are far fewer data that are both quantitative and environmentally relevant (i.e., measured half-lives or rate constants). However, individual transformations and pathways are well documented in the literature. This allows for development of explicitly mechanistic models, making use of established group-contribution approaches, hierarchic rule-based expert systems, and probabilistic evaluation of possible transformation pathways. 

CATABOL is a knowledge-based expert system for the prediction of biotransformation pathways. It works in tandem with a probabilistic model that calculates the probabilities of the individual transformations and overall biochemical oxygen demand (BOD) and extent of C02 production (Jaworska et al., 2002). The model assesses biodegradation based on the entire pathway and not,... 

Boethling, R.S., Gregg, B., Frederick, R., Gabel, N.W., Campbell, S.E., Sabljic, A. (1989) Expert systems survey on biodegradation of xenobiotic chemicals. Ecotoxicol. Environ. Saf. 18, 252-267. 

Expert systems survey on biodegradation of xenobiotic chemicals, Ecotoxicol Environ Safety, Vol. 18, pp. 252-267. 

To our knowledge, up to this date, five expert systems have been developed that claim capabilities in the field of biodegradation of molecules of diverse structures. They are BIODEG Probability Program (BPP), BESS (Biodegradability Evaluation and Simulation System), MultiCASE (Multiple Computer Automated Structure Evaluation, and META (MULTICASE Inc., P.O. Box 22157, Cleveland, OH44122, USA) and the last one, developed by Gamberger et al. ... 

QSAR AND EXPERT SYSTEM STUDIES OF BIODEGRADATION RATES... 

In this section, we will basically describe META, an expert system developed in our laboratory to predict biodegradability and identify biodegradation products. We will also relate other methodologies to it as completely as possible, although little... 

Traditional QSAR and expert system approaches for the prediction of biodegradation on the basis of chemical structure... 

As with the simple example of benzene, there are many ways to modify an API s structure. Well-established test systems, empirical data, rules of thumb " (Figure 7.2) and computer-based systems for the assessment of the properties of molecules, such as biodegradability, are available. Their careful combination allows for the theoretical design of molecules and the assessment of their properties without the need for them to be synthesized. Computer-based systems that assist human experts with the handling of complex knowledge are widely in use within pharmaceutical industries for the optimization of APIs by in silico screening.This allows for a very early and comparatively inexpensive evaluation of the environmental properties of candidates. At the same time, undesirable properties such as mutagenicity can be reduced. This can and should also be done with respect to full mineralization of APIs when they reach the environment. 

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