Physical activity, relationship

When the compound is described using physical, as opposed to structural, descriptors the relationship becomes a PAR (physical-activity relationship). Commonly used physical properties include the octanol-water partition coefficient (log P), water solubility, melting point, boiling point and vapour pressure. Correlations of this type have been used in the perfumery industry to describe and predict the substantivity and retention of fragrance ingredients, that is the ability of a compound to stick to and remain bound to surfaces such as hair, skin or cloth (see Chapter 11 for more details). 

When the property being described is a physical property, such as the boiling point, this is referred to as a quantitative structure-property relationship (QSPR). When the property being described is a type of biological activity, such as drug activity, this is referred to as a quantitative structure-activity relationship (QSAR). Our discussion will first address QSPR. All the points covered in the QSPR section are also applicable to QSAR, which is discussed next. 

Pearlman, R. S. Molecular surface areas and volumes and their use in structure-activity relationships. In Physical Chemical... 

Dohrenwend, Bruce P., Itzhak Levav, Patrick E. Shrout, Sharon Schwartz, Guedalia Naveh, Bruce G. Link, Andrew E. Skodol and Ann Stueve, Socioeconomic Status and Psychiatric Disorders The Causation-Selection Issue , Science 255, no. 5047 (1992) 946-52 Donaldson, Liam, At Least Five a Week Evidence on the Impact of Physical Activity and Its Relationship to Health. A Report from the Chief Medical Officer , Department of Health, 2004 Editorial, A Double-Edged Sword , Nature Reviews Drug Discovery 7 (2008) 275... 

In a study by Andersson et al. [30], the possibilities to use quantitative structure-activity relationship (QSAR) models to predict physical chemical and ecotoxico-logical properties of approximately 200 different plastic additives have been assessed. Physical chemical properties were predicted with the U.S. Environmental Protection Agency Estimation Program Interface (EPI) Suite, Version 3.20. Aquatic ecotoxicity data were calculated by QSAR models in the Toxicity Estimation Software Tool (T.E.S.T.), version 3.3, from U.S. Environmental Protection Agency, as described by Rahmberg et al. [31]. To evaluate the applicability of the QSAR-based characterization factors, they were compared to experiment-based characterization factors for the same substances taken from the USEtox organics database [32], This was done for 39 plastic additives for which experiment-based characterization factors were already available. 

Thiadiazole 1 and its derivatives were used as model compounds for the calculation of molecular parameters related to physical properties for their use in quantitative structure-activity relationship (QSAR) and quantitative structure-property relationship (QSPR) studies <1999EJM41, 2003IJB2583, 2005JMT27>. 

Because of the large number of chemicals of actual and potential concern, the difficulties and cost of experimental determinations, and scientific interest in elucidating the fundamental molecular determinants of physical-chemical properties, considerable effort has been devoted to generating quantitative structure-property relationships (QSPRs). This concept of structure-property relationships or structure-activity relationships (QSARs) is based on observations of linear free-energy relationships, and usually takes the form of a plot or regression of the property of interest as a function of an appropriate molecular descriptor which can be calculated using only a knowledge of molecular structure or a readily accessible molecular property. 

There is a continuing effort to extend the long-established concept of quantitative-structure-activity-relationships (QSARs) to quantitative-structure-property relationships (QSPRs) to compute all relevant environmental physical-chemical properties (such as aqueous solubility, vapor pressure, octanol-water partition coefficient, Henry s law constant, bioconcentration factor (BCF), sorption coefficient and environmental reaction rate constants from molecular structure). 

Pearlman, R. S. (1980) Molecular surface areas and volumes and their use in structure/activity relationships. In Physical Chemical Properties of Drugs. Yalkowsky, S.H., Sinkula, A.A., Valvani, S.C., Eds., Medicinal Research Series, Vol. 10, pp. 321-317, Marcel Dekker, New York. 

Although structurally-diverse as evidenced above, the insecticidal pyrethroids still conform to a unique, operationally-defined, structure-activity relationship based on the physical characteristics and three-dimensional shape of the entire molecule conforming to those originally evidenced in the natural pyrethrins [13]. From this relationship, it becomes apparent that there is no single molecular aspect or reactive moiety that serves as a true toxophore for the pyrethroids and that their actions at target sites are dependent upon the entire stereospecific structure of these insecticides [1]. 

Physical Properties, Transport and Degradation of Environmental Fate and Exposure Assessments, Quantitative Structure-Activity Relationships in Environmental Sciences, VII, Chapter 13, SETAC Press, USA. 

The concept of the similarity of molecules has important ramifications for physical, chemical, and biological systems. Grunwald (7) has recently pointed out the constraints of molecular similarity on linear free energy relations and observed that Their accuracy depends upon the quality of the molecular similarity. The use of quantitative structure-activity relationships (2-6) is based on the assumption that similar molecules have similar properties. Herein we present a general and rigorous definition of molecular structural similarity. Previous research in this field has usually been concerned with sequence comparisons of macromolecules, primarily proteins and nucleic acids (7-9). In addition, there have appeared a number of ad hoc definitions of molecular similarity (10-15), many of which are subsumed in the present work. Difficulties associated with attempting to obtain precise numerical indices for qualitative molecular structural concepts have already been extensively discussed in the literature and will not be reviewed here. 

As the chemical models mentioned here refer to some fundamental thermochemical and electronic effects of molecules, their application is not restricted to the prediction of chemical reactivity data. In fact, in the development of the models extensive comparisons were made with physical data, and thus such data can also be predicted from our models. Furthermore, some of the mechanisms responsible for binding substrates to receptors are naturally enough founded on quite similar electronic effects to those responsible for chemical reactivity. This suggest the use of the models developed here to calculate parameters for quantitative structure-activity relationships (QSAR). 

The recent discovery of a class of peptides, the enkephalins, which act as opiate agonists has led to a number of physical chemical studies aimed at understanding the structure-activity relationships between the enkephalins and the opiates (1 -9). 

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