Intermolecular forces Molecular interactions

The solubility of chemically related compounds decreases with increasing molecular mass since the intermolecular forces of interaction increase. For example, benzene is completely miscible with ethanol, whereas anthracene and ethanol are only partially miscible. The influence of molecular mass on solubility is particularly evident in macromolecules. For example, alcohol, acetone, and acetic acid readily dissolve styrene, but not polystyrene vinyl aeetate dissolves in saturated hydrocarbons and ether, whereas poly(vinyl acetate) does not. Cellulose is insoluble in alcohols, polyfethylene glycol) is insoluble in ethers, poly(vinyl chloride) is insoluble in vinyl chloride, and polyacrylonitrile is insoluble in acetonitrile, even though good solubility would be expected on account of the chemical relation between the polymers and monomers. 

The next point of interest has to do with the question of how deep the surface region or region of appreciably unbalanced forces is. This depends primarily on the range of intermolecular forces and, except where ions are involved, the principal force between molecules is of the so-called van der Waals type (see Section VI-1). This type of force decreases with about the seventh power of the intermolecular distance and, consequently, it is only the first shell or two of nearest neighbors whose interaction with a given molecule is of importance. In other words, a molecule experiences essentially symmetrical forces once it is a few molecular diameters away from the surface, and the thickness of the surface region is of this order of magnitude (see Ref. 23, for example). (Certain aspects of this conclusion need modification and are discussed in Sections X-6C and XVII-5.)... 

The distribution coefficient is an equilibrium constant and, therefore, is subject to the usual thermodynamic treatment of equilibrium systems. By expressing the distribution coefficient in terms of the standard free energy of solute exchange between the phases, the nature of the distribution can be understood and the influence of temperature on the coefficient revealed. However, the distribution of a solute between two phases can also be considered at the molecular level. It is clear that if a solute is distributed more extensively in one phase than the other, then the interactive forces that occur between the solute molecules and the molecules of that phase will be greater than the complementary forces between the solute molecules and those of the other phase. Thus, distribution can be considered to be as a result of differential molecular forces and the magnitude and nature of those intermolecular forces will determine the magnitude of the respective distribution coefficients. Both these explanations of solute distribution will be considered in this chapter, but the classical thermodynamic explanation of distribution will be treated first. 

Molecular interactions are the result of intermolecular forces which are all electrical in nature. It is possible that other forces may be present, such as gravitational and magnetic forces, but these are many orders of magnitude weaker than the electrical forces and play little or no part in solute retention. It must be emphasized that there are three, and only three, different basic types of intermolecular forces, dispersion forces, polar forces and ionic forces. All molecular interactions must be composites of these three basic molecular forces although, individually, they can vary widely in strength. In some instances, different terms have been introduced to describe one particular force which is based not on the type of force but on the strength of the force. Fundamentally, however, there are only three basic types of molecular force. 

When thinking about chemical reactivity, chemists usually focus their attention on bonds, the covalent interactions between atoms within individual molecules. Also important, hotvever, particularly in large biomolecules like proteins and nucleic acids, are a variety of interactions between molecules that strongly affect molecular properties. Collectively called either intermolecular forces, van der Waals forces, or noncovalent interactions, they are of several different types dipole-dipole forces, dispersion forces, and hydrogen bonds. 

The effect of molecular interactions on the distribution coefficient of a solute has already been mentioned in Chapter 1. Molecular interactions are the direct effect of intermolecular forces between the solute and solvent molecules and the nature of these molecular forces will now be discussed in some detail. There are basically four types of molecular forces that can control the distribution coefficient of a solute between two phases. They are chemical forces, ionic forces, polar forces and dispersive forces. Hydrogen bonding is another type of molecular force that has been proposed, but for simplicity in this discussion, hydrogen bonding will be considered as the result of very strong polar forces. These four types of molecular forces that can occur between the solute and the two phases are those that the analyst must modify by choice of the phase system to achieve the necessary separation. Consequently, each type of molecular force enjoins some discussion. 

Pectins are longchain macromolecules. In aqueous solutions they form more or less stiff rods or coils, depending on their degree of branching and linking as well as their molecular weight. In addition interparticular or intermolecular physical-chemical interactions like Van-der-Waals forces, ionic interactions or hydrogen bonds influence the active volume of the molecule, the stiffness and the viscosity. 

As the same types of intermolecular forces are involved, there is no qualitative difference between solute-solvent interactions and the recognition of a compound by a bio (macro) molecular compound. 

A, B and V are constant for a given solute (Eig. 12.4 shows the value of A, 0.78, for atenolol). This means that the balance between intermolecular forces varies with the system investigated as would be expected from a careful reading of Section 12.1.1.3. This can also be demonstrated by using a completely different approach to factorize log P, i.e. a computational method based on molecular interaction fields [10]. Volsurf descriptors [11] have been used to calculate log P of neutral species both in n-octanol-water and in alkane-water [10]. 

The HcReynolds abroach, which was based on earlier theoretical considerations proposed by Rohrschneider, is formulated on the assumption that intermolecular forces are additive and their Individual contributions to retention can be evaluated from differences between the retention index values for a series of test solutes measured on the liquid phase to be characterized and squalane at a fixed temperature of 120 C. The test solutes. Table 2.12, were selected to express dominant Intermolecular interactions. HcReynolds suggested that ten solutes were needed for this purpose. This included the original five test solutes proposed by Rohrschneider or higher molecular weight homologs of those test solutes to improve the accuracy of the retention index measurements. The number of test solutes required to adequately characterize the solvent properties of a stationary phase has remained controversial but in conventional practice the first five solutes in Table 2.12, identified by symbols x through s have been the most widely used [6). It was further assumed that for each type of intermolecular interaction, the interaction energy is proportional to a value a, b, c, d, or e, etc., characteristic of each test solute and proportional to its susceptibility for a particular interaction, and to a value x, X, Z, U, s, etc., characteristic of the capacity of the liquid phase... 

Hybrid MPC-MD schemes may be constructed where the mesoscopic dynamics of the bath is coupled to the molecular dynamics of solute species without introducing explicit solute-bath intermolecular forces. In such a hybrid scheme, between multiparticle collision events at times x, solute particles propagate by Newton s equations of motion in the absence of solvent forces. In order to couple solute and bath particles, the solute particles are included in the multiparticle collision step [40]. The above equations describe the dynamics provided the interaction potential is replaced by Vj(rJVs) and interactions between solute and bath particles are neglected. This type of hybrid MD-MPC dynamics also satisfies the conservation laws and preserves phase space volumes. Since bath particles can penetrate solute particles, specific structural solute-bath effects cannot be treated by this rule. However, simulations may be more efficient since the solute-solvent forces do not have to be computed. 

With the exception of rather small polar molecules, the majority of compounds, including drugs, appear to penetrate biological membranes via a lipid route. As a result, the membrane permeability of most compounds is dependent on K0/w. The physicochemical interpretation of this general relationship is based on the atomic and molecular forces to which the solute molecules are exposed in the aqueous and lipid phases. Thus, the ability of a compound to partition from an aqueous to a lipid phase of a membrane involves the balance between solute-water and solute-membrane intermolecular forces. If the attractive forces of the solute-water interaction are greater than those of the solute-membrane interaction, membrane permeability will be relatively poor and vice versa. In examining the permeability of a homologous series of compounds... 

These models are semiempirical and are based on the concept that intermolecular forces will cause nonrandom arrangement of molecules in the mixture. The models account for the arrangement of molecules of different sizes and the preferred orientation of molecules. In each case, the models are fitted to experimental binary vapor-liquid equilibrium data. This gives binary interaction parameters that can be used to predict multicomponent vapor-liquid equilibrium. In the case of the UNIQUAC equation, if experimentally determined vapor-liquid equilibrium data are not available, the Universal Quasi-chemical Functional Group Activity Coefficients (UNIFAC) method can be used to estimate UNIQUAC parameters from the molecular structures of the components in the mixture3. 

All of these intermolecular forces influence several properties of polymers. Dispersion forces contribute to the factors that result in increased viscosity as molecular weight increases. Crystalline domains arise in polyethylene because of dispersion forces. As you will learn later in the text, there are other things that influence both viscosity and crystallization, but intermolecular forces play an important role. In polar polymers, such as polymethylmethacrylate, polyethylene terephthalate and nylon 6, the presence of the polar groups influences crystallization. The polar groups increase the intensity of the interactions, thereby increasing the rate at which crystalline domains form and their thermal stability. Polar interactions increase the viscosity of such polymers compared to polymers of similar length and molecular weight that exhibit low levels of interaction. 

The term molecular crystal refers to crystals consisting of neutral atomic particles. Thus they include the rare gases He, Ne, Ar, Kr, Xe, and Rn. However, most of them consist of molecules with up to about 100 atoms bound internally by covalent bonds. The dipole interactions that bond them is discussed briefly in Chapter 3, and at length in books such as Parsegian (2006). This book also discusses the Lifshitz-Casimir effect which causes macroscopic solids to attract one another weakly as a result of fluctuating atomic dipoles. Since dipole-dipole forces are almost always positive (unlike monopole forces) they add up to create measurable attractions between macroscopic bodies. However, they decrease rapidly as any two molecules are separated. A detailed history of intermolecular forces is given by Rowlinson (2002). 

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