Lipophilicity pattern

While ionophore-free membranes based on classical ion exchangers are still in use for the determination of lipophilic ions, such sensors often suffer from insufficient selectivity, as it is governed solely by the lipophilicity pattern of ions, also known for anions as the Hofmeister sequence. This pattern for cations is Cs+ > Ag+ >K+ > NH > Na+ > Li+ > Ca2+ > Mg2+ and for anions CIOT > SCN- > I > Sal- > N03- > Br > N02- > Cl- > OAc- HC03- > SO - > HPO4. While the ion exchanger fixes the concentration of hydrophilic analyte ions in the membrane on the basis of the electroneutrality condition within the membrane, the second key membrane component is the ionophore that selectively binds to the analyte ions. The selectivity of... 

The permeability of the human epidermis to many phenolic compounds correlates with their lipophilic pattern. However, phenolic compounds appear to produce denaturation in the skin, and an additional increase in permeability is attributed to the resulting damage to the epidermis. Complications of topical phenol, notably cardiac dysrhythmias, including death, can be caused by phenol face peels (10). 

The drug-receptor interaction is a highly specialized hydrophobic, polar, electronic, and steric interaction the lipophilicity pattern, the electron density distribution, and the polarizability pattern at the surface of both the drug and its binding site contribute to the interaction energy. 

While ionophore-free membranes based on classical ion exchangers are still in nse for the determination of lipophilic ions, such sensors often suffer from insufficient selectivity, as it is governed solely by the lipophilicity pattern of ions, also known for anions as the Hofmeister sequence. This pattern for cations is Cs" > Ag+ >K+ >... 

Statistical analyses based on crystallographic data have been conducted on the cyclodextrins and the results were used to compile contact surfaces/molecular lipophilicity patterns. Pyrolyses of cyclodextrins have been studied by use of a Curie-point pyrolyser. ... 

Figure 7.22b is a similar plot for the other two lipids considered olive oil (unfilled symbols) and octanol (filled symbols). Both lipids can be described by a bilinear relationship, patterned after the case in Fig. 7.19d [Eq. (7.44)]. Octanol shows a declining log Pe relationship for very lipophilic molecules (log Kd > 2). The probe set of 32 molecules does not have examples of very hydrophilic molecules, with log Kd < —2, so the expected hydrophilic ascending part of the solid curve in Fig. 7.22b is not fully shown. Nevertheless, the shape of the plot is very similar to that reported by Camenisch et al. [546], shown in Fig. 7.8c. The UWL in the latter study (stirred solutions) is estimated to be 460 pm (Fig. 7.8b), whereas the corresponding value in unstirred 96-well microtiter late assay is about 2300 pm. For this reason, the high point in Fig. 7.22b is 16 x 10-6 cm/s, whereas it is 70 x 10 6 cm/s in Fig. 7.8c.

Neutral molecules show a range of retention properties between those of acids and bases. Progesterone membrane retention is very high in all cases. Griseofulvin and carbamazepine retention steeply increase with phospholipid content. The patterns of retention follow the lipophilicity properties of the molecules, as indicated by octanol-water apparent partition coefficients (Table 7.4). 

The brain uptake properties of 99m Tc-complexes with the MRP-20 ligand make it and its derivatives potential candidates for rCBF imaging applications. MRP-20 forms a neutral-lipophilic complex with the 99mTcO+3 core by loss of three ionizable protons from the ligand backbone (Fig. 3) [16]. "mTc-MRP-20 and several of its analogues show high brain uptake and retention and exhibit regional cerebral deposition patterns that are related to rCBF [16], This complex is in clinical trials in Europe. 

The patterns of retention follow the lipophilicity properties of the molecules, as indicated by octanol/water apparent partition coefficients. 

Both vacuoles and cytoplasm can be visualized by ester-loading imper-meant fluorochromes. The fluorochrome 6CF can be introduced by ester-loading with 6CF-diacetate, which is not fluorescent or polar and readily permeates cells. Once inside the cell, it is cleaved into the highly fluorescent and charged anion 6CF, which is ion-trapped. Lipophilic FITC derivatives are compartmented in patterns that depend on the subcellular location of esterases, and in different cells may be compartmented by cytoplasm or vacuole (51). 

For two decades, the role of lipophilic chemistry in the evolution of mesograzer host range was heavily influenced by the enemy-free space hypothesis by Hay et al. (1987). This theory predicts that small herbivores consume and inhabit seaweeds that are chemically defended against larger, more mobile herbivores such as fishes and urchins. Support for these patterns can be found in several contexts from temperate North Carolina (e.g., Duffy and Hay 1991, 1994) and New Zealand (Taylor and Steinberg 2005), and the tropical Caribbean (e.g., Hay et al. 1990) and Guam (e.g., Paul 1988 Cruz-Rivera and Paul 2006), and the Antarctic (Huang et al. 

In mammals the cytochrome P-U50 mediated monooxygenase or mixed function oxidase system involved in the elimination of lipophilic environmental contaminants and other foreign compounds, has been implicated in the carcinogen activation process. There are several distinct variants of cytochrome P-U50 in mammalian tissues and there may be more than one form of this ubiquitous cytochrome also in fish. The significance of this lies in the fact that different forms of cytochrome P-U50 result in different metabolite patterns, which in turn may reflect on the carcinogenicity or toxicity of compounds being metabolized. 

The difficulty with HLB as an index of physicochemical properties is that it is not a unique value, as the data of Zaslavsky et al. (1) on the haemolytic activity of three alkyl mercaptan polyoxyethylene derivatives clearly show in Table 1. Nevertheless data on promotion of the absorption of drugs by series of nonionic surfactants, when plotted as a function of HLB do show patterns of behaviour which can assist in pin-pointing the necessary lipophilicity required for optimal biological activity. It is evident however, that structural specificity plays a part in interactions of nonionic surfactants with biomembranes as shown in Table 1. It is reasonable to assume that membranes with different lipophilicities will"require" surfactants of different HLB to achieve penetration and fluidization one of the difficulties in discerning this optimal value of HLB resides in the problems of analysis of data in the literature. For example, Hirai et al. (8 ) examined the effect of a large series of alkyl polyoxyethylene ethers (C4,C0, Cj2 and C 2 series) on the absorption of insulin through the nasal mucosa of rats. Some results are shown in Table II. 

Synthetic musks have been detected in human tissues (Table 8) due to their lipophilic nature and their low biodegradability. The occurrence of these fragrance-related chemicals is subjected to a variable pattern with substantial interindividual differences, opposed to other environmental contaminants such as polychlorinated biphenyls (PCBs) or pesticides [165]. 

A microbial strain may produce more than one siderophore. There are variations in fatty acid chains of a lipophilic part or in the amino acids making up the backbone, as well as released intermediates of the biosynthetic chain. These variations belong all to the same structural pattern. However, there is also the possibility that so-called secondary siderophores are encountered. They constitute a different structural type, usually less complex in their constitution but also less efficient in binding Fe " than the primary ones. Secondary siderophores will be produced when the demand for iron is not so severe or in case there is a genetic defect impeding the production of the primary ones. Examples will be found throughout the review. 

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