Random approach

The random approach involves randomly selecting samples throughout the calibration space. It is important that we use a method of random selection that does not create an underlying correlation among the concentrations of the components. As long as we observe that requirement, we are free to choose any randomness that makes sense. 

In several cases, however, this random approach provided satisfactory results. Thus, the whole group of protected expanded [n]pericyclinones 123-126 was... 

Upon changing the applied strategy from the completely random approach (cf. Scheme 22) to a block assembly, a complete change of the product distribution is observed in the preparation of the protected expanded pericyclinones of type 89 Only the three macrocycles 123,125 and 176 were isolated after the oxidative cyclooligomerization of the dehydrodimer 175 (Scheme 32) [39]. 

Of course, in reality new chemical substances are not synthesized at random with no purpose in mind—the numbers that have still not been created are too staggering for a random approach. By one estimate,1 as many as 10200 molecules could exist that have the general size and chemical character of typical medicines. Instead, chemists create new substances with the aim that their properties will be scientifically important or useful for practical purposes. As part of basic science, chemists have created new substances to test theories. For example, the molecule benzene has the special property of aromaticity, which in this context refers to special stability related to the electronic structure of a molecule. Significant effort has gone into creating new nonbenzenoid aromatic compounds to test the generality of theories about aromaticity. These experiments helped stimulate the application of quantum mechanical theory to the prediction of molecular energies. 

It is important to point out that there is often considerable discussion about the merits of rational approaches where systems are designed, synthesized, and then studied relative to what is sometimes described as the random approach taken with combinatorial chemistry. It is important to view parallel approaches not as a replacement for rational science but as a tool that allows for faster data collection. This data can then be used for the design of better catalysts. 

The beauty of this completely random approach to the analyte detection limit is the direct applicability of the statistical hypothesis testing formalism. Also, long-term trends in calibration slope or backgrounds have little influence. One important assumption is made that the form of the calibration curve [Equation 2c] is fixed. Also, a subtle change has occurred, the operation is no longer linear, with A in the denominator. Thus, the distribution of x is only asymptotically normal, as the relative standard deviation of becomes smaller. 

Baggio, R., Woolfson, M. M., Declercq, J. P., and Germain, G. (1978). On the application of phase relationships to complex structures. XVI. A random approach to structure determination. Acta CrystaUogr. A 34,883-892. 

Thus the completely random approach to the discovery of new MCRs was transformed in a systematic, semi-rational and powerful way. Future research using this elegant approach will certainly reveal many more novel MCRs. 

A more random approach to discovering a lead is the combinatorial chemistry approach (see Chapter 6). This uses a simultaneous multiple synthesis technique to produce large numbers of potential leads. These potential leads are subjected to rapid high throughput biological screening to identify the most active lead compounds. Once identified, these lead compounds are subject to further development. 

Characteristics of composite sampling are that the samples (or measurements) are taken following a random approach and then bulked. The best use is for relatively homogeneous material, unless stratified composites are created. A phase I ESA investigation often uses composite samples. 

Our random approach is apparently more adequate at the higher Si/Al ratios (x<.35). While most samples in that region clearly tend to avoid second-nearest-neighbor Al pairs, the sample with a Si/Al ratio of 5 shows perfect agreement with the random Loewenstein model. It should be noted that this sample differs from the others in that it was not directly synthesized, but was prepared by dealumination of a lower Si/Al ratio sample (i). 

The subdivisions for the possible decisions in this example are shown by the data given in Table 10 and are summarized in Table 11. Thus, in stage 5, there are three possible decisions on the choice of mixer, and each of these has four possible efficiency decisions. In stage 4, there are four possible decisions on temperature level for the heater. In stage 3, there are three possible reactors and two possible catalysts. Stage 2 has three possible decisions of reactor II II or no reactor. In stage 1, there are two possible decisions of one large separator or two small separators. On an overall basis, therefore, the total possible modes of operation by a completely random approach would be... 

A fundamental recipe for preparing combinatorial libraries is the randomization approach known as portion mixing. This technique is also called sptit-and-mix or divide-and-combine [4,5]. In this approach, solid-phase resins containing combinatorial library building blocks are portioned out, coupled, and combined to produce a combinatorial library of compounds. It is a way to synthesize a large... 

Fig. 1. The grid, random, and low-discrepancy sequence approaches to designing the first library in a materials discovery experiment with three compositional variables. The random approach breaks the regular pattern of the grid search, and the low-discrepancy sequence approach avoids overlapping points that may arise in the random approach.

A combination of the SCUBA (see Discrimination by chemical shift, p. 302) and randomization approaches has also been reported under the name RAWSCUBA. In this sequence the solvent resonance is first randomized by a selective ir/2 pulse and gradient pulse combination and then the SCUBA sequence is appUed (i.e. /p/2-composite ir-tjjl) and a final gradient pulse in the opposite direction to the first to dephase the water further. 

The second extreme strategy would be to neglect totally anything which is known in heterogeneous catalysis and randomly to scan combinations of elements in the periodic table. However, this approach does not seem to be very useful, since by this procedure one would, for instance, combine elements that form volatile compounds under reaction conditions which would then ruin the whole library and not be useful under industrial conditions. In addition, the price and availability of certain compounds might restrict the fully randomized approach. 

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