The Polyamines

Polya.mine-Ba.sed Quaternaries. Another important class of quaternaries are the polyamine-based or polyquats. Generally, polyamine-based quaternaries have been used in the same appHcations as their monomeric counterparts (245). Discussions, including the use of polymeric quaternaries in laundry formulations (246) and in the petroleum industry as damage control agents (247), have been pubHshed. 

By virtue of their unique combination of reactivity and basicity, the polyamines react with, or cataly2e the reaction of, many chemicals, sometimes rapidly and usually exothermically. Some reactions may produce derivatives that ate explosives (eg, ethylenedinitrarnine). The amines can cataly2e a mnaway reaction with other compounds (eg, maleic anhydride, ethylene oxide, acrolein, and acrylates), sometimes resulting in an explosion. 

Although connection of polyalkylene or poly(alkylene oxide) groups to the polyamine is most commonly by the succinimide linkage, a different linking group is employed in another important class of ashless dispersants— the Mannich bases. They are prepared on a commercial scale by reaction of an alkylphenol with formaldehyde and a polyamine (173—177). The alkyl and polyamine moieties are similar to those used in the succinimide products. 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

In addition we studied the complexation of ClC+ by the polyamines using microcalorimetry and potentiometry. The enthalpy changes measured are presented as function of the degree of protonation and the amount of CiT bound. 

Eflornithine (difluoromethylornithine, DFMO) inhibits the ornithine decarboxylase of the polyamine pathway, in both the trypanosome and the mammalian cell, by acting as an irreversible competitor of the natural substrate ornithine. Inhibition of ornithine decarboxylase results in depletion of the polyamines, putrescine, spermidine and spermine, which are essential for cell proliferation. Eflornithine selectively harms the parasite and not the mammalian cells, despite acting as an ornithine decarboxylase inhibitor in both cell types. This selectivity is explained by the lower rate of ornithine decarboxylase production in the parasite, as compared to mammalian cells. Due to the high turnover rate, mammalian cells are capable of quickly replenishing inhibited ornithine decarboxylase by newly... 

Adenosylmethionine, the principal source of methyl groups in the body, also contributes its carbon skeleton for the biosynthesis of the 3-diaminopropane portions of the polyamines spermine and spermidine (Figure 31-4). 

The polyamines spermidine and spermine (Figure 31-4) function in cell proliferation and growth, are growth factors for culmred mammalian cells, and stabilize intact cells, subcellular organelles, and membranes. Pharmacologic doses of polyamines are hypothermic... 

S-adenosylmethionine carboxylase is the source of the propylamine in the polyamines spermine and spermidine. The activity of spermine synthase introduces this into spermidine and spermine, which has already been noted. It is worth pointing out that, whereas the inducible histidine decarboxylase... 

Polyalkylene polyamine salts are prepared by contacting polyamines with organic or inorganic acids. The polyamines have a molecular weight of at least 1000 Dalton and ranging up to the limits of water solubility [1185]. In a process of demulsification of the aqueous phase of the broken bitumen emulsions, the pH is adjusted to deactivate the demulsifier so that the water may be used in subsequent in situ hot water or steam floods of the tar sand formation. 

Crosslinking can be achieved also, if the polyamine is modified with a vinyl monomer [283-285], Such mixtures are substantially free of copolymers derived from a polyoxyalkylene glycol and a diglycidyl ether. 

The polyamines putrescine, cadaverine, spermidine, and spermine, which are seen at elevated levels in some victims of cancer, were separated on a Technicon (The Technicon Company Chauncey, NY) TSM Amino Acid Analyzer packed with an 8% divinylbenzene-co-polystyrene sulfonated resin with post-column ninhydrin detection.111 Amines such as ethanolamine, noradrenaline, hexamethylene diamine, methoxytryptamine, spermine, and spermidine were separated from amino acids on a DC-4A cation exchange resin.112 A similar approach, using a Beckman Model 121M amino acid analyzer equipped with an AA-20 column, was also successful.113 A Polyamin-pak strong cation exchange column (JASCO) was eluted with a citrate buffer for the detection of putrescene, spermine, cadaverine, and 1,5-diaminohex-ane from rat thymus.114 A post-column o-phthaldehyde detection system was used. 

Guminski Y, Grousseaud M, Cugnasse S et al (2009) Synthesis of conjugated spermine derivatives with 7-nitrobenzoxadiazole (NBD), rhodamine and bodipy as new fluorescent probes for the polyamine transport system. Bioorg Med Chem Lett 19 2474—2477... 

Biosynthesis of polyamines is essential for growth and multiplication of T. brucei, hence discovery of drug candidates that inhibit enzymes in the polyamine biosynthesis pathway represent an attractive approach to development of trypanocides. The consequences of gene knockout of ornithine decarboxylase (ODC), the target of eflornithine (3), have been further characterized and suggest that new inhibitors of this enzyme may be particularly effective [18]. 

A third enzyme in the polyamine biosynthesis pathway, trypanothione synthetase-amidase (TRYS), has been shown to be essential by both genetic and chemical methods [24]. Specifically, the indazole analog 24 has been identified in a TRYS screen (IC50 = 140 nM) and shown to inhibit growth of wild-type (IC50 = 5.1 pM) and TRYS-dKO (IC50 = 0.46 mM) T. brucei parasites in culture [25]. 

One of the most compelling targets in the polyamine biosynthesis pathway has been S-adenosylmethionine decarboxylase (SAM-DC). This target was chemically validated with the discovery of trypanocidal activity of MDL-73811 nearly two decades ago. Work to understand the unique kinetics for inhibition of this enzyme in T. brucei has shown that a catalytically... 

E. (2003) Biomimetic control of size in the polyamine-directed formation of silica nanospheres. Angewandte Chemie-Intemational Edition, 42, 5192— 5195. 

Cohen, S. S. in "Introduction to the Polyamines" Prentice-Hall Englewood Cliffs, 1971 pp. 29-63. 

The deprotection of the polyamine-thioethers 40a,b can also be accomplished in similar good yields with Li/naphthalene in THF (214). Cleavage of the thioether functions also commenced with [PdCl2(NCMe)2] in the case of 40b (216), and it is likely that the other macrobicycles will also undergo this metal-ion mediated cleavage reaction as well (Scheme 2). Note that this reaction cleaves only one of the two thioether bonds forming a macrocyclic ligand with one thiophenolate and one vinyl-thioether moiety, as... 

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