SUBJECTS polyamines

Macrocyclic polyamines may be viewed as an extended form of linear polyamines 13-161 with one less degree of saturation. Polyamines with lower degrees of saturation, have important biological functions. Compounds such as macrocyclic polyimines 171 and porphyrines 18), function as 02 carriers and activators, promote photosynthesis, form the basic structure of vitamine B12, etc., and for these reasons have been subjects of intense investigation. 

Corrosion inhibiting compositions for metals subjected to highly acidic environments may be produced by reacting in a condensation reaction a styrene/ maleic anhydride copolymer with a polyamine to produce a polyimidoamine inhibitor [1568]. These inhibitors exhibit film-forming and film-persistency characteristics. Some relevant polyamines are listed in Table 6-2. 

The enzymes involved in the polyamine metabolic pathway have been the subject of intensive study, and a number of specific inhibitors for these enzymes have been designed as potential antitumor or antiparasitic agents [166]. Thus, a-difluoromethylornithine, has become a clinically useful agent [167]. Most of the studies involving inhibitors of polyamine metabolism have focused on enzymes involved in the biosynthetic pathway. Recently, there has been considerable interest generated in the enzyme spermidine/spermine-hT -acetyltrans-ferase enzyme (SSAT), the rate-limiting step in the back conversion of polyamines. SSAT, in conjunction with polyamine oxidase (PAO), allows for reversal of the biosynthetic pathway and attenuation of the levels of individual polyamines. 

The subject matter of this chapter will be subdivided into sections concerning template synthesis of the complexes structural and thermodynamic properties of the complexes with synthetic cyclic polyamines complexes with mixed-donor macrocycles reactivity of the complexes cryptates and complexes with phthalocyanines and porphyrins. 

Enantioselective anion sensing is included in a number of reviews covering much broader subjects, namely receptors of anions in general [2-8] and chro-mophoric sensors of anions [9,10]. There are also more specialized reviews dealing with receptors for anions based on macrocyclic polyamines [11], amides [12],... 

Precursors of /1-alanine 3 biosynthesis are uracil 2, L-aspartate 4, and polyamines which are subjected to degradation in distinct ways - whereas uracil is metabolized by hydrogenation followed by hydrolysis, polyamines like spermine 1 are oxidized and L-aspartate is decarboxylated (Scheme 1.6.1). 

In contrast to the polycyclic indole, isoquinoline, or terpene alkaloids, the di- and polyamine alkaloids seem to be of much simpler construction. This first impression is misleading. Special structural features render this group of alkaloids even more difficult to handle than the above-mentioned ones. It should be noted that the structures of several polyamine alkaloids have had to be revised. Because of this, two main factors should be mentioned. (1) The alkaloids sometimes occur as mixtures that are very difficult to separate, and (2) the results from spectral or chemical analyses are equivocal (cf. references on structural elucidation in Section V). This group of alkaloids was the subject of several review papers (26-28) and especially covering the subject of synthesis (29-32). Some general aspects of the difficulties associated with the isolation and structure elucidation of the polyamine alkaloids are discussed. 

The Calu-3 human submucosal gland cell line forms polarized cell monolayers with tight junctions, produces mucus, and develops apical cilia when grown at an air interface. Transport studies can be performed after 10-14 days in culture, and it has been shown that Calu-3 cells express P-gp and actively transport amino acids, nucleosides, and dipeptide analogs organic anions, organic cations, polyamines, and efflux pump substrates are not actively transported.43,51,53-56 Because Calu-3 cells are not subject to the influence of multiple in vivo cell types, the expression of carrier proteins and enzymes may not reflect in vivo levels. Nevertheless, values obtained in Calu-3 permeability studies correlate well with those obtained from primary cultured rabbit tracheal epithelial cells and in vivo rat lung absorption studies.54 Mannitol permeation in Calu-3 cells is about 10 times less than that in vivo, but this is the same ratio difference between Caco-2 cells and in vivo intestinal epithelium.51... 

If the desired product is the pure diamine, a fraction of the polyamines produced is subjected to batch distillation, providing diamine in the distillate. The withdrawal is sent to polyamine storage. 

The most commonly applied methods for the analysis of polyamines in erythrocytes make use of amino acid analyzers and HPLC techniques. A capillary gas chromatographic method with nitrogen-phosphorous detection was applied to the simultaneous determination of 1,3-diaminopropane, putrescine, cadaverine (Cad), spermidine (Sd), and spermine (Sp) in human erythrocytes. Blood samples, collected by venipuncture into EDTA containing Venoject tubes, were subjected to the removal of plasma by centrifugation and erythrocytes were washed three times with two volumes of 0.9% NaCl. The stability of polyamines in erythrocyte suspensions was also investigated. Quantification of polyamines was done by comparing the peak-area ratio of each analyte and its internal standard with that of the standard. The polyamine samples were eluted with 0.1 M hydrochloric acid solutions. The eluate was evaporated to dryness at 120°C under a stream of air and 200 each of acetonitrile and heptafluorobutyric anhydride were added. The isolation of derivatives... 

An alternative for the same kind of analysis are silica columns that have been dynamically coated with a polyamine. Triethylene tetramine or natural amines such as spermidine or putrescine are suitable for this purpose. Small differences in selectivity are observed when different amines ate used. Dynamically coated packings give a more stable chromatography than do amino-propyl bonded phases, but the silica is still subject to slow dissolution. Therefore a silica with a strong skeleton ( = small specific pore volume) is recommended for this application. 

Which of these four potential advantages, if any, actually occurs with the platinum polymers is currently being studied. Approximately two dozen platinum polyamines have been synthesized, and some show biological activity while others do not (126-128). Several of the polymers properties are being explored and correlated with polymer activity in an effort to discover why certain polymers are active while others are inactive. Such factors as the nature of the diamine component, the extent to which a polymer is transported into the cell, the rate of aquation, etc., could all influence the biological activity of a polymer. Two other properties that could control polymer activity are the size of a polymer and the tendency of a polymer to degrade, and these will be the subject of discussion here. 

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