Skip to main content
main-content

Über dieses Buch

Scientists from many disciplines require making observations which are dependent upon the behavior of compounds in solution. This ranges from areas in geography, such as oceanography, to areas in chemistry, such as chromatography, to areas in biology, such as pharmacology. Historically, information would be obtained by observing a response for a given set of conditions and then the conditions would be changed and a new response obtained. In this approach there would be little effort made to actually understand how a compound was behaving in solution but rather just the response was noted. Understanding the behavior of compounds in solution is critical to understanding their behavior in biological systems. This has become increasingly important during the last twenty years as an understanding of the biochemistry related to human illness has become better understood. The development of the pharmaceutical industry and the need to rapidly screen large numbers of compounds has made scientists in the area of drug development aware that the pharmacological activity of compounds can be predicted by knowing their solution physical chemical properties. This is not to say that a specific drug-active site interaction can be predicted but rather a prediction can be made whether or not a compound will be absorbed, transported, or distributed within a physiological system in such a way that an interaction can occur.

Inhaltsverzeichnis

Frontmatter

Chapter 1. Compound Characterization

Why - When - What
Abstract
There probably has never been a time when an attempt was not made to characterize the things about us. This dates back, at least, to the time of Neanderthal man when there existed a need to know if the object they were carrying should be placed on the spit or in the fire. This type of characterization revolved around the senses of sight, sound, and smell, and could also include weight. As time evolved, the degree of sophistication increased but it was not until the discovery of atomic structure that significant advances were made in the methodologies used to characterize the compounds. With the tools of modern chemistry it has become possible to measure the distances between atoms and their positions in a crystal lattice. Not only is it possible to determine the positions of the atoms within a crystal but also the charge or valence state of each. The degree of solvation of a solid substance can be measured and the location of the solvent can be determined, that is, whether the solvent is just on the surface or in the interior of the crystal. Instruments are available which can measure the size of particles only several atoms in diameter. Also, the energy holding the molecules together in a crystal can be determined as well as the most stable configuration of the molecules in the crystal. These are just a few of the types of information which can be obtained on compounds which exist in the solid state.
William H. Streng

Chapter 2. Thermodynamics

What Goes Up Must Come Down
Abstract
Thermodynamics is said not to require a model. The reason for this is that in the area of thermodynamics, relationships between work and energy and the conversion of one to the other are studied. Therefore, the net result, i.e., how much energy or how much work is produced, is the desired information and not how many molecules reacted or explicitly an exact understanding of the reaction path. For example, the heat of melting, which is an endothermic process, can be obtained with the value expressed as joules per gram. Also, the heat of solution, which can be either endothermic or exothermic, has its value expressed as joules per gram. In both of these examples the results do not depend on knowledge of the exact number of molecules melting or dissolving or other interactions which can be occurring, such as solvation, but rather only the initial and final states. This is not to say that a model for the system is not useful when trying to understand what is occurring, only that it is not necessary to have a model for an equilibria in order to obtain a value for an equilibrium constant using thermodynamic measurements.
William H. Streng

Chapter 3. Kinetics

When will it get there?
Abstract
Kinetics, unlike thermodynamics, requires a model in order to understand and interpret the results of experimental data. The reason for this is thermodynamics is only concerned with the initial and final states, whereas kinetics is concerned with the path that is taken.
William H. Streng

Chapter 4. Equilibrium Constants

Standing still in a state of flux
Abstract
In Chapter 3, the statement was made that almost all chemical reactions can proceed in both the forward and reverse directions. However, the extent of the reverse reaction for many reactions is so small that they can be regarded as going to completion. When both the forward and reverse reactions are measurable, the process is called a reversible reaction. (This definition of a reversible reaction should not be confused with the term reversible used in a thermodynamic process. In a thermodynamic reversible process the reactions occur at an infinitely slow rate, while the reactions for a chemical reaction are spontaneous and, therefore, occur at a finite rate.) Looking at a system at chemical equilibrium on a macro scale, there is no change in composition with time if there is no change in temperature or pressure. This does not mean that the system is static; in fact, it is dynamic on a micro scale. The forward and reverse reactions continue, but their rates of change are equal. Therefore, the statement can be made that a system can be considered to be standing still while in a continuous state of flux. In order to arrive at the necessary relationships describing the equilibrium constant either a kinetic (state of flux) or a thermodynamic (standing still) approach can be taken.
William H. Streng

Chapter 5. Partition Coefficient

Where has it gone?
Abstract
Place a solute in a solvent and there is little doubt what will be the concentration of the solution. If a second immiscible solvent is added to the mixture, the concentration in the first solvent will become less than originally present. Immediately the question needs to be asked, “Where has it gone?” Analysis of the concentration of the solute in each of the solvents will reveal that the solute has distributed itself between the two solvents. The ability of a compound to penetrate membranes is critical to its ability to be active pharmacologically. If a compound cannot penetrate into membranes, or cannot be transported through membranes, it will be impossible for the compound to get to the site where it needs to act. One property that is used to indicate the ability of a compound to penetrate membranes is its distribution coefficient or partition coefficient. The normal procedure used to determine the partition coefficient is to measure the equilibrium concentrations of the compound in two immiscible liquid phases which are in contact. The two phases are an aqueous solvent and an immiscible organic solvent. The organic solvent is usually n-octanol but occasionally other solvents such as chloroform are used.
William H. Streng

Chapter 6. Solubility

Who’s the best?
Abstract
There was a park near my house when I was growing up and during the summer months a group of us boys would go there and divide into two teams to play baseball. Usually everyone was selected to be on one of the teams but the wait could be agonizingly long for those of us who were likely to be among the last selected. Everyone wanted to be one of the first ones selected because that would mean that they were considered to be one of the better players. However, the fact that someone was selected first did not mean that they were the best in all areas. Joe could hit the ball a mile and make super catches in the outfield, but he could not pitch and did strike out more than some others; Don was a good pitcher, but he certainly did not hit the ball very far; and Jack could play in the infield like no one else on either team. As the teams were chosen, the same few would be among the last. There was George who was just a great kid and everyone wanted to be around but did not play ball well; Bob made everyone laugh and so he would be chosen; then it would be my turn. I tended to be a holdout with the expectation that my contract would be re-negotiated, but, to no avail, and I would always be put in the position where I could cause the least amount of damage. This was not all bad for me since it allowed me the time to think about science (this was before girls) but as a result my career as a baseball player was significantly affected.
William H. Streng

Chapter 7. Aqueous Solubility of Weak Acids and Bases

A chameleon in disguise
Abstract
During my formative years I did not have the opportunity to visit areas which had tropical or subtropical climates. Almost all of my activities were in the humid continental climate zone with brief excursions into the subarctic and middle-latitude desert and steppe climate zones. After I had started graduate school, I had the opportunity to experience, with much delight, the world which exists in the humid subtropical and tropical savanna climate zones. On the surface nothing seemed much different. This trip occurred during the winter months and there was snow on the ground where I left and the temperatures were about 30 °C (86 °F) where I was visiting, but beyond this there did not appear to be anything strikingly different. However, upon closer scrutinization, I found that there were many things which were not the same. Hanging from the trees, high voltage wires and phone lines was Spanish moss - a plant which grows on other plants but which gets its food, water and minerals from the air. There were many birds around but these species were much different from those I was accustomed to seeing. While there were deciduous and conifer trees, again the species were much different. I was not familiar with the salt water fish since all of my fishing experience had been in fresh water lakes. Lastly, some of the mammals encountered were quite different ranging from the manatee, found in the bayous and tributaries along the ocean, to alligators.
William H. Streng

Chapter 8. Solution Stability

It’s all about change
Abstract
Rain collects in the cracks and crevices of the rocks located on the faces of mountains. As the temperature decreases and the water freezes, small pieces of the rocks will split off and fall. These splinters of rocks form the well known talus slopes found at the base of the mountains.
William H. Streng

Chapter 9. Instrumentation

Growth and Expectation
Abstract
I have had the distinct pleasure of being able to watch my children grow from birth to adulthood. From the time they would lie in their crib and follow the movements of objects with their eyes to the first time they took the car out when they were teenagers to the time when they got married, I had to marvel at the changes in their abilities and assuredness. Of course, I would like to say that without me these changes would not have taken place but I know that would not be true. Today it is known that everyone is a product of both their environment and their genes and, therefore, I did have some influence upon their final set of traits. As they became older, their growth was also challenged by an increase in expectation. They would be given more latitude as they became older and at the same time they would be expected to behave or conduct themselves in a more adult manner. This expectation continues into adulthood and everyone is judged accordingly.
William H. Streng

Chapter 10. Equilibria: Experimental Procedures and Examples

It’s all interpretation
Abstract
How often have we been told that a new study has shown that something we have believed or have been doing is not correct and has been conclusively refuted, only to find out six months or a year later that the “new” study was not correct. Recently, there were many articles published in which it was claimed that eggs should not be eaten because of the risk of elevating the levels of cholesterol in the blood. More recently, it was reported that some eggs would not be harmful. Before this, it was announced that all cholesterol was bad and a move was in place to try and reduce its presence in serum to the lowest levels possible. The cholesterol found in serum has since been shown to be composed of several different types and that there is a need for some in serum. This recantation or evolution of theory is not a new phenomenon but has probably existed ever since mankind began. Take for instance the different models used for the universe. The first models used for the universe put the earth as a flat plane with the stars circling around it. Some cultures put the plane of the earth resting on the back of a turtle. The Greeks believed the earth to be round but they also believed it was the center of the universe with everything revolving around this center. As recently as the first part of the 1900s a static model was used to represent the universe. Even Einstein believed, when he first proposed the Theory of Relativity, that the universe was not changing.
William H. Streng

Chapter 11. Partitioning: Experimental Procedures and Examples

It’s all interpretation
Abstract
When a compound is placed in a system composed of two immiscible solvents, the distribution of the compound was shown in Chapter 5, Eq. (5.4), to be directly related to the difference between the standard state free energies for the compound in the two solvents. Since the standard state free energies are constant for a specific system, this difference will also be constant and a partition coefficient is therefore an equilibrium constant. As long as the system remains constant, that is, the temperature and components do not change, the partition coefficient for a specific species will not change. Under these conditions the partition profile can be determined with, for instance, a change in pH. In this chapter the results of partitioning studies using several techniques will be discussed.
William H. Streng

Chapter 12. Solubility: Experimental Procedures and Examples

It’s all interpretation
Abstract
As discussed in Chapters 6 and 7, there is no “best solvent” for all compounds and, after selecting a solvent, conditions in the system can be changed which will affect the properties of the compound. If a compound is uncharged it will, in general, be more soluble in solvents having lower dielectric constants, although, if the compound has polarizable groups or a dipole, then, protic solvents or solvents possessing a dipole will be better solvents. Solvents having higher dielectric constants, protic solvents and solvents which possess a dipole will be better solvents for compounds which have charges. Those compounds which are uncharged can be treated according to Hildebrand theory to obtain estimates of the solubility in different solvents. A solubility theory has not been developed for charged compounds which can be applied without imposing empirical relationships to specific types or classes of compounds. The difficulty in being able to develop a generalized theory for the solubility of charged compounds is that the solute-solvent and solvent-solvent interactions are much more important in protic and dipolar solvents and these interactions change with changes in concentration. It is with this in mind that the solubilities of several compounds in different types of solvents will be discussed.
William H. Streng

Chapter 13. Solution Kinetics: Experimental Procedures and Examples

It’s all interpretation
Abstract
In Chapters 3 and 8 kinetics and many of the factors which can influence the stability of solutions were discussed. It was mentioned that in order to interpret the results from experiments conducted to determine the stability of a compound, a model was required. At times the model which is chosen is very general while at other times the model will have great detail. While the amount of information which can be obtained will depend on the detail of the model, at times sufficient information can be obtained with a model which does not describe the path of the reaction or other controlling factors. From an academic perspective, the argument can easily be made that kinetic studies should be designed which will provide all the information needed to fully understand the disappearance of the compound and the appearance of new compounds. This would allow the prediction of the behavior of the compound under any condition to which it might be exposed. Usually the studies are set up to answer a specific question and, in this case, limited information is obtained. Often, the overriding factor is the amount of time needed to conduct the study and then only those factors which are suspected of playing a significant part in the stability of the compound will be investigated.
William H. Streng

Backmatter

Weitere Informationen