Product-based design

Library design methods can be divided into reactant-based or product-based design. In reactant-based design, reactants are chosen without consideration of the products that will result. For example, diverse subsets of reactants are selected in the hope they will give rise to a diverse library of products. In product-based design, the selection of reactants is determined by analyzing the products that will be produced. 

Reactant-based design is computationally less demanding than product-based design, since there are fewer molecules to consider. Consider a two-component reaction where there are 100 examples of each type of reactant. Now assume that the aim is to design a library of 100 products with configuration 10 x 10, i.e., 10 examples of each reactant. There are approx 1013 different possible subsets of size 10 contained within 100 compounds, as determined by the equation below ... 

Once the reactant pools have been filtered, the next step in product-based designs is usually to enumerate the full virtual library. This can be a very time-consuming step and hence a useful precursor can be to enumerate carefully chosen subsets that will give an indication of the success or otherwise of the full virtual experiment. Thus, in a two component reaction it can be useful to take the first reactant in the first pool and combine it with all the reactants in the second pool (to generate 1 x nB products). This should then be followed by the enumeration of one reactant in the second pool with all reactants in the first pool to give nA x 1 products. If either of these two partial enumeration steps fail, then the full enumeration will also fail. Thus, troublesome reactants can be identified early. 

Reagent-Based Versus Product-Based Design... 

Product-based selection is much more computationally demanding than reagent-based selection. Typically, it requires the computational enumeration of the full virtual combinatorial library and calculation of the descriptors for all possible products, prior to the application of a subset selection method. Consider a three-component reaction with 100 reagents available at each substituent position and assume that the aim is to build a 10 x 10 x 10 combinatorial library. In reagent-based selection, this requires the calculation of descriptors for 300 compounds (100 + 100 + 100). In product-based design, however, the full library of 1 million compounds (100 x 100 x 100) must be enumerated and descriptors must be calculated for each product molecule. 

The size of a virtual library can be reduced by applying filters to eliminate reagents that are known to be undesirable [67]. However, in some cases, the virtual library may still be too large to allow full enumeration, and thus full product-based design is infeasible. (Although the need for full enumeration may not be necessary in the future, for example, Barnard et al. [82] have recently developed a method for the rapid calculation of descriptors for the products in a virtual combinatorial library that avoids the need for enumeration.)... 

Product-based design, on the other hand, involves generating mXn product structures within virtual libraries very early on in the design process, and properties as well as molecular descriptors are to be calculated for those. An addi-... 

Despite being questioned in a recent publication (8), it is generally believed that product-based design is generating better designs in terms of diversity and coverage. 

Figure 1.176 shows a carbon fiber prototype mold for a 400-liter fuel tank with a simplified frame and screwed form flanges. The attachment of required fixtures like a fuel-level sensor, threaded fittings, inserts, etc. enables the rotation of prototypes in production-based design. 

---