Discovery , additional rules

Additional Rules for Discovery (Non-GLP) PK Assays Requiring QC Samples (Level III)... 

Table 13.3 Additional rules for discovery (nonGLP) PK assays requiring QC samples (level III). Adapted from [6], with permission from Taylor and Francis Group.

From Tsai s pioneering discoveries [25,27], we know that atomic size, electronegativity, and valence electron counts play substantial roles in the formation of QCs. These criteria are expressed by the Hume-Rothery rules [30,31]. However, three additional highlights are also important in the consideration of possible candidate systems, at least from the viewpoint of chemists. 

Earlier experience has shown that stoichiometric reactions of ABa(V, A (A electropositive metal, B and C electronegative main-group or late transition metals) with e/a of about 1.7-2.3 are a good rule-of-thumb way to generate Tsai-type AC/QCs. This time, suitable reactions of CaAuxGa6-x provided both 1/1 and 2/1 ACs [87]. In addition, investigations of phase widths for both ACs also led to the discovery of the first Al-free 1/0 AC, CaAu3Ga [88]. 

In the new vision, assay cycle time is dramatically reduced and the criteria used to measure assay acceptability are matched to sample type. Early screening samples may be assayed using simple methods and minimum numbers of standards. Samples from early preclinical PK studies in rats and other species may require additional standards. Finally, for PK studies performed in the lead characterization phase, one might add quality control (QC) samples. One set of rules for non-GLP assays has been codified in a recent publication.16 These rules make it possible to match the assay cycle time with the in-life cycle time in order to minimize the total discovery cycle time. 

The discovery of a cluster of six face-sharing [M6N] octahedra, shown in Figure 3.1-7, in a compound that contained 14 additional Na atoms per cluster, seemed to violate the validity of Miedema s rule, because the central atom refined perfectly as K in the X-ray structure determination. 

Following our success in finding a suitable silane and catalyst for the first step in the synthesis of unsymmetrical bis-alkoxy si lanes, we set out to evaluate catalysts to achieve the second alcoholysis. We were aware from prior reports in the literature that there were a variety of catalysts capable of performing alcoholysis of silanes.10 17 From prior evaluation of catalysts in the first step, we knew that 10 % Pd/C, Rh2(pfb)4, and CuH all catalyze the reaction of the second step with diethylsilane and Rh2(pfb)4 catalyzes the reaction of the second step (10 %) with diphenylsilane (Table 4). Rli2(OAc)4 was ruled out by our discovery that only one addition of alcohol occurred with diisopropylsilane. 

The control of the legiochemistiy of addition of organometallic a-enones, a-enals and a-ene esters has attracted the attention of many chemists from the early age of organic chemistry. Not only have a-sele-noalkyllithiums not escaped the rule, but fundamental discoveries made at the occasion of this work have been successfully extended to other organometallics. ... 

The enormous growth in organometallic chemistry over the last fifty years and the discovery of new classes of compounds with unprecedented bonding modes has resulted in the need for additional nomenclature rules for organometallic compounds. This Chapter is therefore considerably expanded over Section 1-10.9 of Ref. 1 and is largely based on the IUPAC recommendations published in 1999 for organometallic compounds of the transition elements.2... 

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