Physicochemical properties, molecular

Modified QCMs GCM schemes often consider extra contributions. These contributions can be physicochemical properties, molecular descriptors, and various correction factors. For example, to estimate the critical temperature, Tc, the input of the normal boiling point, Tb, is required by certain GCMs [33]. In this case a typical approach is based on the modification of eq. 1.6.3 as follows ... 

In this chapter we describe some methods used to determine the kinetics of the action of hyaluronidase. Thble 2 presents a survey of the Michaelis-Menten constants (Km) of the action of hyaluronidase on hyaluronan and chondiootin sulfate obtained using different methods. These assays usually make use of hyaluronan as a substrate for hyaluionidase. Various sources of hyalmonan are employed, but these arbitrates have different physicochemical properties (molecular weight intrinsic viscosity). Payan el al [130] investigated the action of Streptmnyces hyahnonidase on hyaluronan from several sources. 

One can describe a molecule in many ways and the same applies to bioisosteres. Molecular descriptor methods are covered in the third part by the application of different representations. A number of computational approaches to bioisosteric replacement are covered in chapters on physicochemical properties, molecular topology, molecular shape, and the use of protein structure information. Each chapter covers many common methods and overviews of when best to apply these methods, and where they have been successfully applied. 

Keywords Ab initio methods Binary ionic liquid mixtures Hydrogen bonding Meta-analysis and physicochemical properties Molecular simulation Structure-affecting interactions... 

Furthermore, most physicochemical properties are related to interactions between a molecule and its environment. For instance, the partitioning between two phases is a temperature-dependent constant of a substance with respect to the solvent system. Equation (1) therefore has to be rewritten as a function of the molecular structure, C, the solvent, S, the temperature, X etc. (Eq. (2)). 

An extensive series of studies for the prediction of aqueous solubility has been reported in the literature, as summarized by Lipinski et al. [15] and jorgensen and Duffy [16]. These methods can be categorized into three types 1 correlation of solubility with experimentally determined physicochemical properties such as melting point and molecular volume 2) estimation of solubility by group contribution methods and 3) correlation of solubility with descriptors derived from the molecular structure by computational methods. The third approach has been proven to be particularly successful for the prediction of solubility because it does not need experimental descriptors and can therefore be applied to collections of virtual compounds also. 

These first components of the autocorrelation coefficient of the seven physicochemical properties were put together with the other 15 descriptors, providing 22 descriptors. Pairwise correlation analysis was then performed a descriptor was eliminated if the correlation coefficient was equal or higher than 0.90, and four descriptors (molecular weight, the number of carbon atoms, and the first component of the 2D autocorrelation coefficient for the atomic polarizability and n-charge) were removed. This left 18 descriptors. 

C. Tomlin, ed.. The Pesticides Manual A World Compendium, Incorporating the Agrochemicals Handbook, 10th ed.. The British Crop Protection Council and The Royal Society of Chemistry, Crop Protection PubHcations, Cambridge, U.K., 1994. Includes 725 entries by common name in alphabetic order, with chemical stmcture, chemical name(s), molecular formula, CAS Registry Number, physicochemical properties, commercialisation, mode of action, uses, trade names, analytical methods, mammalian toxicology, ecotoxicology, and environmental fate. 

Increasing attention has been paid to the generation of quantitative stmcture—activity relationships in which the effects of molecular substitution on pharmacologic activity can be interpreted in terms of the physicochemical properties of the substituents. These approaches are based on the extrathermodynamic analysis of substituent effects (36) ... 

In subsequent studies attempting to find a correlation of physicochemical properties and antimicrobial activity, other parameters have been employed, such as Hammett O values, electronic distribution calculated by molecular orbital methods, spectral characteristics, and hydrophobicity constants. No new insight on the role of physiochemical properties of the sulfonamides has resulted. Acid dissociation appears to play a predominant role, since it affects aqueous solubiUty, partition coefficient and transport across membranes, protein binding, tubular secretion, and reabsorption in the kidneys. An exhaustive discussion of these studies has been provided (10). 

Several physicochemical properties of dietary fiber contribute to its physiological role. Water-holding capacity, ion-exchange capacity, solution viscosity, density, and molecular kiteractions are characteristics determined by the chemical stmcture of the component polysaccharides, thek crystallinity, and surface area. 

A chemical must have certain physicochemical properties to elicit an endocrine disrupting effect. For example, the ability to enter the body and to cross the cell membrane into the cellular medium requires a degree of lipophilicity. Fipophilic potentials may be compared by reference to the chemical s octanol-water coefficient (usually expressed as log K ). This property, together with molecular size and chemical structure, has an important influence on the bioacciimiilation... 

Position in the microsphere Molecular weight Physicochemical properties Concentration... 

Partitioning or cell-based methods provide an absolute measure of the chemical space covered by a collection of compounds. They are based on the definition of a low-dimensional chemistry space, for example, one based on a small number of physicochemical properties such as molecular weight, calculated logP, and number of hydrogen bond donors [45]. Each property defines an axis of the chemistry-space. The range of values for each property is divided into a set of bins, and the combinatorial product of all bins then defines the set of cells or partitions that make up the space. 

In 1868 two Scottish scientists, Crum Brown and Fraser [4] recognized that a relation exists between the physiological action of a substance and its chemical composition and constitution. That recognition was in effect the birth of the science that has come to be known as quantitative structure-activity relationship (QSAR) studies a QSAR is a mathematical equation that relates a biological or other property to structural and/or physicochemical properties of a series of (usually) related compounds. Shortly afterwards, Richardson [5] showed that the narcotic effect of primary aliphatic alcohols varied with their molecular weight, and in 1893 Richet [6] observed that the toxicities of a variety of simple polar chemicals such as alcohols, ethers, and ketones were inversely correlated with their aqueous solubilities. Probably the best known of the very early work in the field was that of Overton [7] and Meyer [8], who found that the narcotic effect of simple chemicals increased with their oil-water partition coefficient and postulated that this reflected the partitioning of a chemical between the aqueous exobiophase and a lipophilic receptor. This, as it turned out, was most prescient, for about 70% of published QSARs contain a term relating to partition coefficient [9]. 

A close relationship exists between physicochemical properties of pigment molecules and their ability to be absorbed and thus to exhibit biological functions. Carotenoids are hydrophobic molecules that require a lipophilic environment. In vivo, they are found in precise locations and orientations within biological membranes. For example, the dihydroxycarotenoids such as lutein and zeaxanthin orient themselves perpendicularly to the membrane surface as molecular rivets in order to expose their hydroxyl groups to a more polar environment. 

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