Non-ionizable moieties

The most frequently employed solubilization approaches using non-ionizable moieties involve hydroxylated and poly-oxymethylenic side chains or glucosides and their analogs. 

Purines are constructed from a rr-electron-deficient pyrimidine moiety and a rr-excessive imidazole system. As the rr-electron excess of the imidazole moiety is strongly reduced by the t-deficient pyrimidine system the C8 atom becomes the most electron deficient site in the non-ionized molecule and a substituent at this position is normally displaced first by a nucleophile. The order of nucleophilic displacement reactions is C8 > C6 > C2. Anion formation at the imidazole nitrogen increases the electron density of the imidazole system. As a consequence, nucleophilic attack is now directed to the pyrimidine moiety with C6 as the most reactive position followed by C2 and C8. 

The POPs we consider in this chapter are non-ionizable, and largely non-polar. These characteristics make them poorly soluble in water and thus hydrophobic. Introduction of an ionizable functional group, such as a sulfate or conjugate as occurs with metabolism, greatly increases the water solubility of hydrophobic compounds (due to hydration of the ionizable moieties), and such modified compounds are rapidly... 

Several types of amino groups can he biotransformed by acetylation, including arylamino, aliphatic amino, a-amino, hydrazine, and sulfonamide groups. The addition of the acetyl group generally ma,sks the amine group with a non-ionizable acetyl moiety, producing xenobiotics that are les.s water soiuble than the parent compound. Despite this, in some cases acetylation still facilitates urinary excretion. 

G. Attachment of the solubilizing moiety to carboxylic acid functionalities Non-ionizable Side Chains... 

Tyr fluoresces with far less intensity than the non-ionized form and redshifts to 345 nm. Tryptophan has a quantum yield very close to that of Tyr but absorbs far better and so fluoresces (A = 287 nm 2f = 348 nm) more intensely. The nitrogen-containing indole moiety in Trp becomes protonated at low pH thus decreasing its fluorescence. The fluorescence of Trp is also quenched at high pH and so Trp fluoresces best over a range in pH from 4 to 9. The fluorescence properties of these amino acids as mentioned apply only to the free amino acids in solution. Such properties can change significantly when they become part of a protein. 

An excess (5 1 mole ratio) of ethyl diazoacetate is used in these reactions to suppress cyclobutadimerization or Diels-Alder cyclodimerization. In difunctional molecules which have non-equivalent ionizable functionalities, cyclopropanation is highly selective for the more easily oxidized functionality. The latter selectivity is perhaps the most attractive aspect of the reaction. In contrast to transition metal (e.g. rhodium) catalyzed cyclopropanations, cation radical additions to electron deficient alkene moieties do not occur at all. The reaction is relatively sensitive to... 

Modem instruments offer novel sophisticated modes to detect non-target analytes. If the fragmentation behavior of a compound class is known, this can be used to find derivatives of these compounds even though the sfructure of the complete molecule is unknown. If X represents the characteristic moiety of a compotmd class, which is attached to any moiety R, let us assume two hypothetic fragmentation pathways (fragmentation of anions is chosen because most PFC metabolites are ionized negatively) ... 

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