Activity Molecular structures

Orthophosphoric acid containing three acid OH groups in the molecule offers many opportunities for the realization of surface-active molecular structures. But phosphoric acid also possesses the ability to form polyacids in an widespread manner. Pyrophophoric acid and triphosphoric acid are substances that have been known for a long time. This presents further possibilities for interesting synthesis. 

The pharmacodynamically active molecular structure of the calcium channel blocker, nifedipine, is photodecomposed by UV-VIS radiation (8). This effect is manifested by a change in color (from yellow to colorless) or the fading of colored preparations, formation of precipitation and alteration of the taste of the product. Such changes during storage may give patients the sense of uneasiness, confusion, and doubt as to the safety and efficacy of the product. 

Thus, dissymmetric molecules commonly have a simple axis of symmetry, and in asymmetric molecules this axis is absent however, both species are usually optically active. In liquid crystal systems both types of material are capable of exhibiting chiral properties. Table 1 summarizes the relationships between optical activity, molecular structure, and rotational symmetry operations [1]. 

Table 1. Relationships between optical activity, molecular structure, and rotational symmetry operations (after Eliel [1]).

This spectrum is called a Raman spectrum and corresponds to the vibrational or rotational changes in the molecule. The selection rules for Raman activity are different from those for i.r. activity and the two types of spectroscopy are complementary in the study of molecular structure. Modern Raman spectrometers use lasers for excitation. In the resonance Raman effect excitation at a frequency corresponding to electronic absorption causes great enhancement of the Raman spectrum. 

Information if data are put into context with other data, we call the result information. The measurement of the biological activity of a compound gains in value if we also know the molecular structure of that compoimd. 

In chemoinformatics, chirality is taken into account by many structural representation schemes, in order that a specific enantiomer can be imambiguously specified. A challenging task is the automatic detection of chirality in a molecular structure, which was solved for the case of chiral atoms, but not for chirality arising from other stereogenic units. Beyond labeling, quantitative descriptors of molecular chirahty are required for the prediction of chiral properties such as biological activity or enantioselectivity in chemical reactions) from the molecular structure. These descriptors, and how chemoinformatics can be used to automatically detect, specify, and represent molecular chirality, are described in more detail in Chapter 8. 

All the techniques described above can be used to calculate molecular structures and energies. Which other properties are important for chemoinformatics Most applications have used semi-empirical theory to calculate properties or descriptors, but ab-initio and DFT are equally applicable. In the following, we describe some typical properties and descriptors that have been used in quantitative structure-activity (QSAR) and structure-property (QSPR) relationships. 

A challenging task in material science as well as in pharmaceutical research is to custom tailor a compound s properties. George S. Hammond stated that the most fundamental and lasting objective of synthesis is not production of new compounds, but production of properties (Norris Award Lecture, 1968). The molecular structure of an organic or inorganic compound determines its properties. Nevertheless, methods for the direct prediction of a compound s properties based on its molecular structure are usually not available (Figure 8-1). Therefore, the establishment of Quantitative Structure-Property Relationships (QSPRs) and Quantitative Structure-Activity Relationships (QSARs) uses an indirect approach in order to tackle this problem. In the first step, numerical descriptors encoding information about the molecular structure are calculated for a set of compounds. Secondly, statistical and artificial neural network models are used to predict the property or activity of interest based on these descriptors or a suitable subset. 

Another technique is to use pattern recognition routines. Whereas QSAR relates activity to properties such as the dipole moment, pattern recognition examines only the molecular structure. It thus attempts to find correlations between the functional groups and combinations of functional groups and the biological activity. 

Once a number of lead compounds have been found, computational and laboratory techniques are very successful in rehning the molecular structures to yield greater drug activity and fewer side elfects. This is done both in the laboratory and computationally by examining the molecular structures to determine which aspects are responsible for both the drug activity and the side effects. These are the QSAR techniques described in Chapter 30. Recently, 3D QSAR has become very popular for this type of application. These techniques have been very successful in the rehnement of lead compounds. 

Because there is little fragmentation on FD, it is necessary to activate the molecular or quasi-molecular ions if molecular structural information is needed. This can be done by any of the methods used in tandem MS as, for example, collisional activation (see Chapters 20 through 23 for more information on tandem MS and collisional activation). 

Typical MS/MS configuration. Ions produced from a source (e.g., dynamic FAB) are analyzed by MS(1). Molecular ions (M or [M + H]+ or [M - H]", etc.) are selected in MS(1) and passed through a collision cell (CC), where they are activated by collision with a neutral gas. The activation causes some of the molecular ions to break up, and the resulting fragment ions provide evidence of the original molecular structure. The spectrum of fragment ions is mass analyzed in the second mass spectrometer, MS(2). 

L. R. Nassimbeni and M. L. Niven, in International Union of Crystallography, eds.. Molecular Structure - Chemical Reactivity and Fiological Activity, Oxford University Press, Oxford, 1988. 

Simple collision theory does not provide a detailed interpretation of the energy barrier or a method for the calculation of activation energy. It also fails to lead to interpretations in terms of molecular structure. The notable feature of collision theoiy is that, with very simple means, it provides one basis for defining typical or normal kinetic behavior, thereby directing attention to unusual behavior. 

Apart from finding structures that give energy minima, most molecular mechanics packages will calculate structural features such as the surface area or the molecular volume. Quantities such as these are often used to investigate relationships between molecular structure and pharmacological activity. This field of human endeavour is called QSAR (quantitative structure and activity relations). 

---