Nuisance compounds

Once samples are acquired, voucher specimens must be maintained according to standard accepted methods and the collected specimens must be extracted or otherwise processed to prepare samples for biological evaluation. The goal of sample handling and preparation is to select for positives (remove nuisance compounds), prepare the samples to be compatible with existing (and future) bioassays, and store both the collected unprocessed material and the processed samples in a manner that is easily retrievable and maximizes stability. 

Plants are not different from other natural product samples in that they too tend to interfere with various screening formats in nonspecific ways as nuisance compounds displaying unwanted color, inherent fluorescence, promiscuous or aggregate behaviors, detergent-like activities, or toxicity (Feng et al., 2005 Appleton, Buss, and Butler, 2007). Biochemical assays (cell-free defined systems) are notoriously sensitive to such interference by natural product extracts. Cell-based reporter assays and cell-based so-called phenotypic screens always require parental cell controls to determine extract toxicity. However, plants contain their own sets of components that are problematic to screening assays and compound identification. 

As important as validation studies for synthetic samples are in running a successful discovery program, they are even more important for running natural product samples and especially plant extracts, which are notoriously difficult to run in biochemical or enzyme-based screens. Tannins in particular are responsible for nonspecifically inhibiting activities in such screens. Other nuisance compounds include chlorophyll, melanin, lipids, and waxes. 

In general terms, dereplication refers to the differentiation of a compound of interest from nuisance compounds, e.g. a novel structure from known natural products. 

The isolation of the bioactive constituent(s) from a given biomass can be a challenging task, particularly if the active constituent of interest is present in very low amounts. The actual procedure will depend to a large extent on the nature of the sample extract a marine sample, for example, may well require a somewhat different extraction and purification process from that derived from a plant sample. Nevertheless, the essential feature in all of these methods is the use of an appropriate and reproducible bioassay to guide the isolation of the active compound. It is also extremely important that compounds that are known to inhibit a particular assay, or those that are nuisance compounds be dereplicated (identified and eliminated) as early in the process as possible. Procedures for doing this have been discussed, " and various new approaches to isolation and stracture elucidation have been reviewed. ... 

Activated carbon generally presents no particular health hazard as defined by NIOSH (62). However, it is a nuisance and mild irritant with respect to inhalation, skin contact, eye exposure, and ingestion. On the other hand, special consideration must be given to the handling of spent carbon that may contain a concentration of toxic compounds. 

Copper discharges to the global biosphere are due primarily to human activities, especially mining, smelting, and refining copper and the treatment and recycling of municipal and industrial wastes. Some copper compounds, especially copper sulfate, also contribute to environmental copper burdens because they are widely and intensively used in confined geographic areas to control nuisance species of aquatic plants and invertebrates, diseases of terrestrial crop plants, and ectoparasites of fish and livestock. 

Toxic compounds are frequently rendered less toxic by electrochemical treatment, for instance dehalogenation of chlorinated derivatives such as PCBs or AOX (performed in a divided cell or in the absence of Cl ions in a monocell) odors are eliminated or greatly reduced, i.e. reduction of nitrotoluene which can be a serious odor nuisance biodegradability is improved. Elimination of colloids and surfactants is possible. 

Most activated esters are crystalline compounds that can be stored for subsequent use. A variety of properties are exhibited by the various esters. All esters mentioned in this monograph (see Section 2.9) except succinimido esters generate a hydroxy compound that is insoluble in water when aminolyzed. Elimination of this material can be a nuisance in some cases. Nitrophenols are not readily soluble in alkali a trace is sufficient to produce a yellow color in the solution of the reaction product. 

In addition to the removal of solids from gases, the problem of small quantities of compounds causing odour nuisance must frequently be handled. Activated carbon filters are used for this purpose and, in continuous operation, gaseous impurities from the air-stream are adsorbed on the activated carbon granules. The carbon will frequently adsorb contaminants until they reach a level of 20-30 per cent of the mass of the carbon. 

For the prevention of nuisance therefore there are two possibilities. First, the formation or release of odorous chemical species can be discouraged. In practice this usually means the prevention of reducing conditions (negative redox potential) and possibly the prior removal of certain key compounds. Second, the time of contact between the sludge/ slurry and the air can be reduced, for example by ploughing in or sub-surface injection, and the act of spreading can be timed to coincide with favourable atmospheric conditions. These two approaches can of course be used in combination. 

For most odour nuisance problems, chemical plants, refineries, livestock production, food processing, rendering, water purification plants etc., the compounds responsible for the odour are known. So chemical analysis of the odour can be limited to these odorants, and selective concentrating techniques can be used. Selective concentrating methods are based on specific absorption techniques, using particular chemical reactions of odorant classes. Sometimes several absorption methods have to be used in order to describe the odour problem, thus increasing the labor cost of the analysis. On the other hand absorption methods allow better quantitative results. Selective absorption of odorants from air produces a far less complex mixture. We developed or are developing several of these methods for aldehydes, amines, acids, thiols etc. 

---