Transamination polymer

Additionally, the authors chose 3-chloropropionyl chloride as the immobilized building block in order to carry out a ring-expansion approach, which led to the generation of a 14-member library of thioxotetrahydropyrimidinones [85, 86], The initially prepared polymer-bound chloropropionyl ester was efficiently transformed into the corresponding diamines by transamination utilizing several primary amines. These diamine intermediates could also be obtained by treatment of the pure polymeric support with acryloyl chloride and subsequent addition of the appropriate amines (Scheme 7.74). 

Transactinides, 1 491—499, 492t Transalkylation, 12 162 acrylamide polymers, 1 315 reaction, 23 329 side reactions in, 23 329 Transamination... 

The first method in this application, however, was limited to modifying alcohol-containing colorants onto polymers containing grafted succinic anhydride transesterification, and transaminated reactions were also reported. In the second method water-soluble colorants were prepared by azo coupling of colorants with alkoxyether functionalized aniline. 

B-Aminoborazines are of particular interest for fundamental studies. In these compounds, boron is bonded to three nitrogen atoms with two different types of environment. B-Aminoborazines are also useful precursors for the synthesis of thermally stable polymers. Quite a few polycondensates of aminoborazines and copolymerisates with organic difunctional molecules have been described 4>. Of major interest are difunctional borazines yielding linear polycondensates. The condensation of l,3,5-tris(2,6-dimethylphenyl)-2,4-dichloroborazine (cf. Section II.2.5) with aliphatic, aromatic, and heterocyclic diamines, as well as the preparation of the same linear polyborazines by transamination of 1,3,5-tris(2,6-dimethylphenyl)2,4-bis(diethyl-amino)borazine with diamines was studied 139). 

The PEI-pyridoxamine polymer was treated with excess pyruvic acid in various buffer solutions, without added metal ions and with excess added EDTA. Kinetic studies revealed that the attached polymer increased the rate of pyridoxamine transamination with pyruvic acid by a factor of6700-8300 at pH 5.0. Under higher pH conditions, the rate enhancement decreased At pH 7.0 the rate enhancement by the polymer was still 2300 times, while at pH 8.0, the optimum for pyridoxamine itself, it was 1900. We also found that transamination by simple pyridoxamine showed strong metal ion catalysis - adding 1 equiv. of CuCl2 per pyridoxamine unit to the pH 5.0 solution increased the... 

The rate enhancement of the polymer over that of simple pyridoxamine was a steep function of the length of the alkyl chains added, in polymers with roughly the same percentage of alkylation and of pyridoxamine attachment. At pH 7.0 and 30 °C, the acceleration over the rate with pyridoxamine was 160 for C-l chains, 180 for C-3, 500 for C-6, 1000 for C-9, 2300 for C-12, and 2500 for the C-15 and C-18 normal alkyl chains. This chain effect seems unlikely to involve hydrophobic binding of a substrate as hydrophilic as pyruvic acid. Instead the hydrophobic chains modify the pK,s of the amino groups in the polymer and also create a cavity in which the transamination can take place in a less than fully aqueous environment. 

To study the effect of polymer size on catalysis [37], pyridoxamine was linked to a series of PEIs with Mn = 600,1800,10 000, and 60 000, both simply permethylated and with additional attached dodecyl chains. The polymers were examined in the transamination of pyruvic acid and of phenylpyruvic acid, showing Michaelis-Menten behavior. The k2 and of i M determined showed only small variations with polymer size. Thus, the strong advantage of pyridoxamines attached to the Mn = 60 000 PEI, relative to simple pyridoxamine alone, was seen to almost the same extent with the smaller... 

By the appropriate selection of reaction conditions and reactants, transamination processes can be directed to the selective formation of new sil-ylamines, disilazanes, volatile oligomeric polysilazanes, soluble higher molecular weight polysilazanes, or highly cross-linked insoluble polymers. 

Highly branched and even cross-linked polysilazane polymers are also desirable, particularly for the formation of ceramic powders. The transamination of Tris and vinyl-Tris with ammonia is a convenient process for the preparation of these precursors. The reactions were effectively catalyzed by strong acids such as trifluoroacetic acid ... 

Tris transaminates readily with ammonia or primary amines when catalyzed by carbon dioxide or strong organic acids. The polysilazane products range from discrete solid disilazanes, to liquid distillable oligomers, and to highly cross-linked infusible polymers. Some of these polysilazanes can be pyro-lyzed to amorphous silicon nitride or mixtures of silicon nitride and silicon carbide below 1550 or to crystalline ceramics above that temperature. 

The transformations themselves involved reactions of ketoacids with a pyridoxamine unit, either covalently attached to the polymer or reversibly bound to the hydrophobic core (29), which converted the ketoacids to amino acids, and the pyridoxamine was converted to a pyridoxal unit either covalently attached to the polymer or reversibly dissociated from the polymer. This reaction was modeled directly on the transamination process observed in natural enzymes. However, the second part of a full transamination in nature is the reaction of the pyridoxal with a different amino acid, which runs the transamination backward to form the pyridoxamine again while converting the new amino acid into its corresponding ketoacid. We found that such a process was too slow in our biomimetic system and could not compete with the rapid aldol condensation of the ketoacids with the pyridoxal. 

Liu L, Zhou W, Chruma JJ, Breslow R. Transamination reactions with multiple turnovers catalyzed by hydrophobic pyridoxamine cofactors in the presence of polyethylenimine polymers. J. Am. Chem. Soc. 2004 126 8136-8137. 

The possibility to tailor-make MIPs towards a desired selectivity in combination with the high stability of the materials under a broad range of conditions has rendered MIPs attractive for the development of synthetic enzymes [243, 244]. A popular strategy has been to imprint a transition state analog to obtain a polymer that reduces the activation energy of the reaction. Catalytically active groups are often included in the polymer network. This approach has been applied towards ester and amide hydrolysis reactions [245, 246]. Examples of other reactions where MIPs have been utilized as enzyme mimics are isomerization [247], transamination [248], Diels-Alder reaction [249], 3-elimination [250] and regioselective cycloaddition [251]. 

A somewhat unconventional access to preceramic polymers containing silicon and boron has been reported by Schmidt et al. A borazine polymer and a silazane polymer are separately synthesized and dissolved in toluene, and then mixed together. The subsequent crosslinking of the borazine with the silazane components proceeds through hydrogen elimination and transamination reactions [54]. 

Like homogeneous catalysis, the removal of a-hydrogen of the amino acid fragment by OH ions, the local concentration of which is apparently high in the polymer phase, is probably the rate-determining step of heterogeneous racemization. Under similar conditions, the rate of a-amino acid racemization decreases in the sequence Ala = Ser>Phe>Nva>Lys>Val, and correlates with the rate of substrate racemization in the presence of Schiff bases and transamination of amino acids by pyridoxal phosphate. 

In the described examples, the pyridoxamine was covalently attached to the polymer while in most real transaminase enzymes the pyridoxamine coenzyme forms a noncovalent active holoenzyme with the protein (apoenzyme). A new artificial transaminase mimic was developed, in which the pyridoxamine binds noncovalently and reversibly to the polymer. The pyridoxamine attached, for example, to a steroid side chain 99 or 100, together with modified PEI 101 (molecular weight of 60000 and 8.7% dodecyl chains) forms the artificial holoenzyme (Figure 38a). The transamination of pyruvic acid was accelerated 28000-fold with 99 + 101 compared to 10 000 with the covalent pyridoxamine-polymer 98 enzyme mimic. This was due to the fact that the noncovalent system 99 - -101 is more dynamic and therefore can adopt a more suitable geometry for the reaction. The artificial transaminase shows effective rate enhancements in converting the ketoacid into the amino acid, but also the pyridoxamine is converted to pyridoxal. The conversion to pyridoxamine is a necessary step in the catalytic cycle to achieve high turnovers however, this was still not possible with the noncovalent model system. It was observed that the reverse process is very slow and actually in all artificial models so far thermodynamically unfavorable. However, it was possible to use sacrificial amino acids at elevated temperatures (60 °C) that were decarboxy-lated to recycle the pyridoxal 102 to pyridoxamine 100 with modest turnover numbers of 81 (Figure 38b). " ... 

Further studies on artihcial transaminases were done by Breslow et al. by attaching the pyridoxamine to a PAMAM dendrimer (Figure 39). In contrast to the PEI polymer 101, which has not a well-defined structure, it is possible to build more structurally defined transaminase models with one pyridoxamine unit at the core of a PAMAM dendrimer. However, this dendrimeric transamination mimic 103 and even further recent dendrimeric transaminase enzyme mimics developed by Breslow et al. were not as potent as the polymeric ones described above. 

Furthermore, oxime formation has been used to funetionalize proteins for example, N-terminal oxidation of interleukin 8 with sodium periodate and biomimetic transamination of myoglobin with pyridoxal-5-phosphate, followed by site-specific protein EGylation with hydrojgrlamine-functionalized polymer blocks. The selectivity of this reaction is limited by the fact that other amino acids within the protein ean be oxidized as well, and incomplete and unselective transamination can take plaee. ... 

The results presented in Table 4 might indicate a significant pattern that reinforces the transamination hypothesis. Using a standard heating rate of S CYmin for the pyrolysis process, we obtained a hi er level of residual carbon in a dirm relationship with the increased steric hindrance of the polymer toward the transamination reaction. 

Reaction of the hydrochloride derivative of the PEI fraction of a MW of 1800 liberated 94% of the anticipated hydrogen within a few hours. In contrast with this the 10000 MW fraction produced only 86% of the theoretical amount of H2. These two materials were obtained as free flowing powders after solvent evaporation which retained the sodium chloride by-product. Attempts to separate the salt by ultrafiltration or dialysis were partially effective because the polymers behaved as ion exchangers and retained chloride ions. An alternate synthetic approach to the cyanoborane derivatives which would not produce salt as a byproduct was explored. In this case, previously formed pyridine.BH2CN was used in a transamination reaction with neutral PEI producing a derivative that showed 59% derivatization. Attempts to derivatize polyallylamine hydrochloride, PAA, by reaction with NaBH3CN failed even in boiling water under reflux. Apparently this marked difference with PEI stems from differences in pKa values of the two hydrochlorides which was measured to be about 5.0 for PEI and 7.0 for PAA. 

Figure 1.15 A pyridoxamine residue attached to a polymer that also carries hydrophobic chains so that substrates are strongly bound in water and transaminated with very large accelerations.

A munber of polymers that contain Ge-N bonds in the backbone have been reported. For example, Yoder and Zuckermann synthesized germanium imidazo-lidines using transamination between dimethyl-Z)w-(dieihylamino)-germane and... 

---