Molecular forces intermolecular

Halgren T A 1996b. Merck Molecular Force Field II MMEF94 van der Waals and Electrostatic Parameters for Intermolecular Interactions. Journal of Computational Chemistry 17 520-552. 

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. 

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. 

Halgren TA. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J Comput Chem... 

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... 

Thermodynamics describes the behaviour of systems in terms of quantities and functions of state, but cannot express these quantities in terms of model concepts and assumptions on the structure of the system, inter-molecular forces, etc. This is also true of the activity coefficients thermodynamics defines these quantities and gives their dependence on the temperature, pressure and composition, but cannot interpret them from the point of view of intermolecular interactions. Every theoretical expression of the activity coefficients as a function of the composition of the solution is necessarily based on extrathermodynamic, mainly statistical concepts. This approach makes it possible to elaborate quantitatively the theory of individual activity coefficients. Their values are of paramount importance, for example, for operational definition of the pH and its potentiometric determination (Section 3.3.2), for potentiometric measurement with ion-selective electrodes (Section 6.3), in general for all the systems where liquid junctions appear (Section 2.5.3), etc. 

In van der Waals equation, it is the term n2a/V2 that is of interest in this discussion, because that term gives information about intermolecular forces. Specifically, it is the parameter a that is related to inter-molecular forces rather than the number of moles, n, or the volume, V. It should be expected that the... 

At the same time that Dalton proposed his ideas on partial pressure, he developed the concept of vapor pressure. A vapor is the gaseous form of a substance that normally exists as a solid or liquid. A gas is a substance that exists in the gaseous states under normal conditions of temperature and pressure. The vapor pressure of a liquid is the partial pressure of the liquid s vapor at equilibrium. Liquids with strong inter-molecular forces exert lower vapor pressures than those with weak intermolecular forces. In liquids with strong intermolecular forces, it is more difficult for the molecules to leave the liquid state and enter the gaseous state. 

Why is it that some substances readily mix to form solutions while others do not Whether one substance dissolves in another substance is largely dependent on the inter-molecular forces present in the substances. For a solution to form, the solute particles must become dispersed throughout the solvent. This process requires the solute and solvent to initially separate and then mix. Another way of thinking of this is that the solute particles must separate from each other and disperse throughout the solvent. The solvent may separate to make room for the solute particles or the solute particles may occupy the space between the solvent particles. Determining whether one substance dissolves in another requires examining three different intermolecular forces present in the substances—between the... 

In the second step the bas is recognized by the receptor site and the bas-rep complex forms. As was noted above, the complex is generally bonded by inter-molecular forces. The bas is transferred from an aqueous phase to the receptor site. The receptor site is very much more hydrophobic than is the aqueous phase. It follows, then, that complex formation depends on the difference in intermolecular forces between the bas-aqueous phase and the bas-receptor site. The importance of a good fit between bas and receptor site has been known for many years. The configuration and conformation of the bas can be of enormous importance. Also important is the nature of the receptor. If the receptor is. a cleft, as is the case in some enzymes, steric effects may be maximal as it may not be possible for a substituent to relieve steric strain by rotating into a more favorable conformation. In such a system, more than one steric parameter will very likely be required in order to account for steric effects in different directions. Alternatively, the receptor may resemble a bowl, or a shallow, fairly flat-bottomed dish. Conceivably it may also be a mound. In a bowl or dish, steric effects are likely to be very different from those in a cleft. Possible examples are shown in Fig. 1, 2, and 3. 

Israelachvili, J. N., Intermolecular and Surface Forces, 2d ed., Academic Press, New York, 1991. (Undergraduate and graduate levels. The best reference available currently on the topic. Many examples of the application of surface forces in biological systems. The links between molecular forces and surface forces and the relation between molecular forces and bulk properties of materials are discussed in a manner accessible to advanced undergraduate students.)... 

The numerical value of a liquid s vapor pressure depends on the magnitude of the intermolecular forces present and on the temperature. The smaller the inter-molecular forces, the higher the vapor pressure because loosely held molecules escape more easily. The higher the temperature, the higher the vapor pressure because a larger fraction of molecules have sufficient kinetic energy to escape. 

Within a liquid, molecules are surrounded by other molecules. Each molecule exerts an intermolecular force of attraction on surrounding molecules. The molecular force exerted by each molecule is equal in all directions. 

Surface energy is a direct manifestation of intermolecular forces. The molecules at the surface of a liquid or a solid are influenced by unbalanced molecular forces and therefore possess additional energy, in contrast with the molecules inside the liquid or solid. 

Intermolecular forces are the attractive forces that hold molecules and ions together. These forces should not be confused with the intramolecular forces that hold the atoms together in a covalent molecule (see Lesson 11, Molecular Structure ). Intermolecular forces are grouped into four classifications, each supporting the existence of the condensed states of matter solids and liquids. In addition, these forces can also explain the nonideal behavior of certain gases. 

The term solvation refers to the surrounding of each dissolved molecule or ion by a shell of more or less tightly bound solvent molecules. This solvent shell is the result of inter-molecular forces between solute and solvent. For aqueous solutions the term used is hydration. Intermolecular interactions between solvent molecules and ions are particularly important in solutions of electrolytes, since ions exert specially strong forces on solvent molecules. Crude electrostatic calculations show that the field experienced by nearest neighbours of dissolved ions is 10. .. 10 V/cm. Fig. 2-7 shows a highly simplified picture of such an interaction between ions and dipolar solvent molecules. 

The study of the rotation-vibration spectra of polyatomic molecules in the gas phase can provide extensive information about the molecular structure, the force field and vibration-rotation interaction parameters. Such IR-spectra are sources of rotational information, in particular for molecules with no permanent dipole moment, since for these cases a pure rotational spectrum does not exist. Vibrational frequencies from gas phase spectra are desirable, because the molecular force field is not affected by intermolecular interactions. Besides, valuable support for the assignment of vibrational transitions can be obtained from the rotational fine structure of the vibrational bands. Even spectra recorded with medium resolution can contain a wealth of information hot bands , for instance, provide insight into the anharmonicity of vibrational potentials. Spectral contributions of isotopic molecules, certainly dependent on their abundance, may also be resolved. 

---