Ethylenimine derivatives

Since the formation of the ethyleniminium ion is crucial for the cytotoxic activity of the nitrogen mustards, it is not surprising that stable ethylenimine derivatives have antitumor activity. Thiophospho-ramide or thiotepa is the best known compound of this type that has been used clinically. Both thiotepa and its primary metabolite, triethylenephos-phoramide (TEPA), to which it is rapidly converted by hepatic mixed-function oxygenases form crosslinks with DNA. It is mainly used as an intravesicu-lar agent in bladder cancer. Thiotepa produces little toxicity other than myelosuppression. 

Ethylenimine derivatives can be made to undergo nucleophilic substitution reaction to give a wide variety of substituted ethylenimines. 

Based on this rationale, a series of bis(l-aziridinyl)phosphinyl carbamates was synthesized102 in which alkylating ethylenimine derivatives were... 

Organo-tin and -silicon steroids have been prepared from 3a- and 3)S-halocho-lest-anes and 5-enes, and a number of steroidal esters of p-[AfAT-bis(2-chloro-ethyl)amino]phenylacetic acid and sulphides derived from p-bis(2-chloroethyl)-amino-thiophenol and ethylenimine derivatives of steroids have been prepared. The substituted phenylacetates showed good inhibition of certain tumours. ... 

The hydrolysis of nitrophenyl sulphates is not, contrary to an earlier report, catalysed by poly(ethylenimine) derivatives, although that of dinitrophenyl sulphates is substantially enhanced by partly quarternized polymer. ... 

The effect of added anions on the decarboxylation of 6-nitrobenziso-oxazole-3-carboxylate by poly(ethylenimine) derivatives has been reported. The versatility... 

Numerous other derivatives of guar have been prepared by attaching modifying molecules to the guar backbone. Illustrative of the modifying molecules are chloroacetic acid(122), acrolein(123), ethylenimine(124), acrylamide(125), aminomethylphosphonic acid(126), and methyl bromide(127). None of these have achieved widespread use... 

Ethylenimine Brochure 125-521-65, Midland (Mich.), Dow Chemical Co., 1965 Explosive silver derivatives may be formed in contact with silver or its alloys, including silver solder, which is therefore unsuitable in handling equipment. 

Figure 1.92 The small compound ethylenimine can react with sulfhydryls to form aminoethyl derivatives.

Figure 1.93 2-Bromoethylamine can be used to transform a thiol into an amine. The reaction may proceed through the intermediate formation of ethylenimine, yielding an aminoethyl derivative.

Several derivatives of the highly reactive aziridine (ethylenimine) show explosive instability. Individually indexed compounds are f Aziridine, 0863 1,1-Biaziridinyl, 1593... 

Despite the fact that alkylating agents exhibit a common mechanism of action, their clinical use varies depending on differences in pharmacokinetics, metabolism, hpid solubility, ability to penetrate membranes, and toxicity. They can be classified as nitrogen-containing mustard derivatives (mechorethamine, chlorambucil, melfalan, cyclophosphamide, ifos-famide), derivatives of ethylenimine (thiotepa), nitrosoureas (carmustine, lomustine, strep-tozocin), alkylsulfonates (busulfan), and derivatives of platinum (cwplatin, carboplatin). 

As Fig. 15b illustrates, the graphical relation appears to be linear for an interaction number of 3 to 4, if A 1. Alternatively, for A = 1, linearity is evident (Fig. 15c) when the interaction number is 5 to 6. Thus a large value of A is compatible with the smallest interaction number. Excimer formation occurs within the fluorescence lifetime, about 8 nsec. Within that time the pyrene-labeled amine side chains must approach within about 4 A of each other. For the 5.3% pyrenylpolyethylenimine derivative in ethanol, where no ground-state association occurs, the effective local concentration of pyrene on the polymer matrix is about 10-2 M, as calculated from excimer fluorescence. In aqueous solution, where clusters form within the polymer matrix, the effective local concentration of pyrene adduct must be even greater. The quantitative assessment of fluorescence intensities (Fig. 15) points to a minimum interaction number of 3 to 4 pyrenyl-labeled amine side chains, within the 8 nsec lifetime. Since A 1, it appears from (12) that kDM(A) kMD + kD. Thus excimer formation must be very rapid in the polymer environment. We can conclude, therefore, that the primary-amine side chains of poly-ethylenimine are very flexible and mobile. 

The dimensions of the three-membered ring m determined by measurement of the microwave spectrum286 68>887 and electron -diffraction spectrum 80 of ethylenimine vapor and the X-ray diffm tion of a crystalline derivative (VTI)186 are summarized in Table 1 -Sinoe the bond lengths are very nearly equal, the internal bond angles must be close to 60 , compared -with 111,3° for the C-—N—C bimd angle in dimethylamine. 

Ethylenimine reacts with xanthates to give a thi eolidine derivative ao (Eq. 67) and with hydrogen sulfide plus various ketones to give dialkyl thiazolidines 6 (Eq. 58). 

Ethylenimine is alleged to react with carbon dioxide at low temperatures to give a vinylamjne derivative, but the product is extremely unstable and not well characterized31 (Eq. 75). "... 

The acid-catalyzed ring openings of ethylenimine and 2-ethyl-ethylenimine have also been characterized as A-2 reactions (Earley et al., 1958). The entropies of activation are —9-4 and —10.0 e.u., respectively. However, AS for the reaction of 2,2-dimethylethylenimine is —1.9 e.u., suggesting incursion of the unimolecular mechanism, a conclusion which is supported on other grounds (Earley et al., 1958). The volume changes of activation have also been measured (Earley et al., 1958). These results, if interpreted in terms of Whalley s (1959) criterion, would indicate the A-l mechanism for ethylenimine and the A-2 for the ethyl and dimethyl derivatives, a conclusion which seems unacceptable. 

In the literature, linear polymers are referred to as poly(iminoethylene), and branched polymers as poly(ethylenimine), since the latter derive from the ring-opening polymerization of ethylenimine. In this review, both polymers will be referred to as PEI. Mention will be made, however, to their structure whenever opportune. 

Alternatively, MW-assisted acid hydrolysis using 6 m HC1 at 100-110°C under anaerobic conditions can be used to hydrolyze proteins [32]. Conflicting results as to the stability of selenomethionine have been reported in the literature [133, 140-142]. Stability is probably dependent on sample matrix and procedural variations. Selenocysteine is widely reported to be unstable [143], and normally is reacted with either l-fluoro-2,4-dinitrobenzene, iodoacetic acid, or ethylenimine to form a stable 2,4-dinitrophenyl, carbomethyl or aminoethyl derivative before hydrolysis [137, 144-146]. 

A variety of mono-, di-, tetra-, and polydendron PAMAMs have been synthesized from simple amines as well as linear polyamine cores [2, 83, 124]. Linear poly(ethylenimines) with core multiplicities (Nc of ca. 300-400) have been shown to produce high-aspect ratio, rod-like dendrimers at generation 3 or 4 [2]. Their length is determined by the degree of polymerization (n) of the initiator core and their diameter is derived from the number of generations (see Scheme 3). 

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