Ligand deconvolution

Screening of compound libraries with medium throughput is only possible if the spectra can be recorded in a short period of time, and if one measurement gives simultaneously a number of answers. In practice, several ligands are usually measured in one protein sample, depending on the problem [5]. Mostly 10-20 ligands are combined to multiplexes, which need to be deconvoluted if a positive answer, as shown in Fig. 1 is obtained. The hits obtained maybe analyzed automatically or by hand through manual inspection of the spectra. 

There are two principal modes of coordination of the carbon monoxide ligand in transition metal carbonyls terminal coordination, to a single metal atom, and bridging coordination, to two or more metal atoms. The Ols spectrum of Co4(CO)12, shown in Fig. 5, can be readily deconvoluted into two peaks corresponding to these two types of carbonyl groups109. This spectrum is useful for determining the relative chemical shifts for the two types because... 

Table 3.1 A portion of the membership of the ALIS screening library, composed of NG LI 27A443 (library 3 in this table) and four other libraries, which yields DHFR ligand 1 (NCD-157, entry 11). Compounds of similar exact molecular weight (EMW) are distributed among the five pooled libraries to minimize mass overlap and simplify hit deconvolution. Reprinted from [40] with permission from Elsevier.

In the retesting and deconvolution phase of the procedure new compound mixtures were made based on the results of primary screening. These contained from nine to 14 compounds and no monoisotopic mass redundancy. Since most mass spectrometric peaks picked as hits in the primary screen contain more than one compound, and only one compound per peak is likely to be a binder, the nonmass redundant retest mixtures are unlikely to contain more than a few bona fide ligands, so once again target excess is maintained. Both the initial (round zero,... 

Figure 14.5 DR-UV spectra of (a) Ti-silsesquioxanes complexes, with the assigned major species for each maximum, and (b) the Ti(OPr )4 grafted on MCM-41 and deconvolution. The fifth ligand in the pentacoordinated species is represented as an adjacent surface siloxane bridge, but water or surface silanols are also possible (see text). (From Reference [64].)...

Although isotopic patterns and deconvolutions may be calculated manually (6), to achieve full potential a computer is virtually a necessity. Manual calculations often omit the 1.1% contribution for for molecules with large ligands, thirty carbons are not unusual, and these would give a 33% contribution to the m/e value, greater than that from the nominal mass by one mass unit. 

Fig. 19 Polymerization reaction of oxetane and CO2 catalyzed by (salen)CrCl and two equivalents of n-Bu4NBr at 70°C (salen ligand contains a cyclohexylene backbone for the diimine and t-butyl substituents in the 3,5-positions of the phenolates). (a) Three-dimensional infrared traces of the closely overlapped VCO2 bonds of TMC and poly(TMC). (b) Reaction profile as a function of time, where only a select number of composite infrared bands were deconvoluted...

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