Monomers Adenine Derivatives

A nucleotide base-imprinted polymer membrane has been reported in which methacrylic acid was used as a functional monomer for the imprinting of an adenine derivative, 9-ethyladenine [41], A free-standing film was prepared by polymerizing a DMF solution containing methacrylic acid and ethylene glycol dimethacrylate on a silanized glass slide at 65-70 °C under nitrogen atmosphere. 

Homopolymers of methacryloyloxyethyl-type monomers containing 5-FU, thymine, or adenine were very stable toward acids and bases, while their hydrophilic copolymers were found to be degraded in aqueous solution under mild conditions to give the derivatives of purine and pyrimidines. The derivatives released from the copolymers were identified by UV spectroscopy as N-hy-droxyethyl derivatives of 5-FU, thymine, or adenine after isolation by preparative TLC. This means that the ester groups of the polymer side chains were hydrolyzed in aqueous solution. 

From the values of the monomer reactivity ratios, the relative reactivity of the monomers toward the growing free radicals derived from MAOThe, MAOA and MAOU (t, a and u, respectively) was estimated (Table 6). As for the growing radical of MAOThe (t), for example, the reactivities of MAOThe and MAOU monomer are equal but higher than that of MAOA monomer in ethanol solution while the reactivities of these monomers are nearly equal in dioxane solution. The copolymerization proceeds predominantly under the influence of base-base pairing between adenine and uracil rings. 

The most extensive work in this area has been on the vinyl-type derivatives of uracil and adenine and this research has been reviewed recently These monomers Include 1-vinyl-... 

Block copolymers produced from the sequential polymerization of exo-N-bulyl-7-oxabicyclo 2.2.1 hcpl-5-ene-2,3-dicarboximide and another nor-bornene derivative carrying an adenine group were employed using a ruthe-niirm catalyst, as shown in Scheme 38 [99]. The first monomer was polymerized in CH2CI2 at room temperature followed by the addition of the second monomer and succinimide. In the presence of succinimide the conversion of the adenine-containing monomer was almost quantitative, probably due to the formation of hydrogen bonds with the adenine moiety, which prevents any undesired interaction with the catalyst. Monomodal peaks were obtained by SEC analysis with polydispersity indices ranging from 1.20 up to 1.60. 

The NMR results show that, in the case of 3 and 5 nucleotides, the binding of metal, or at least copper, does occur at Nj for adenine and guanine and at Ni for cytosine very little binding of copper occurs in thymine, the methyl derivative of uracil. NMR studies have also shown us that in the polymeric nucleic acids binding occurs generally in the same position as in these monomers. For example, in polyadenylic acid, the binding is also at Nj, and in polycytidylic acid it is at Ni. 

In the case of DNA, a D-2-deoxyribose molecule is combined to each of the bases to form a nucleoside, and the nucleosides are then combined with each other with a phosphoric acid to form a polymer (DNA). On the other hand, in the case of RNA, D-ribose, instead of D-2-deoxyribose, is combined to each of the bases to form a nucleoside, and as in the case of DNA, these nucleosides are combined with each other to form a polymer (RNA). Among the bases within DNA and RNA, adenine and guanine have been described in the preceding section. In this section, cytosine, thymine, and uracil, which are pyrimidine bases, will be described. Purine derivatives exist as a constituent unit of nucleic acids and as many kinds of monomers, and these are also present in natural products, such as caffeine, inosinic acid, and cytokinin. On the other hand, as natural products, pyrimidine derivatives are rather rare. Nucleosides composed of pyrimidine bases cytosine, thymine, and uracil coupled with D-ribose are known as cytidine, thymidine, and uridine, respectively. Among these alkaloids, cytidine was first isolated from the nucleic acid of yeast [1,2], and thymidine was isolated from thymonucleic acid [3,4]. In the meantime, uridine was obtained by the weak alkali hydrolysis [5] of the nucleic acids originating from yeast. 

A very interesting method of polycondensation of active esters containing nucleic acid bases with diamines was described by Hattori and co-workers (87). Di-p-nitrophenyl methylsuccinate with thymine or theophylline was condensed with piperazine. The reaction was carried out in a pyridine/methylene chloride mixture or dimethyl formamide (DMF) in the presence of a copolymer of styrene and styrene derivatives with adenine groups as a template. The strong interaction between the complementary groups (adenine in the template and thymine in the monomer) leads to the template effect. The maximum acceleration effect was observed for copol5uners with adenine content about 54% in the case of polycondensation with piperazine. 

Other synthetic applications of the phosphazene bases include the use of Bu -Pl (37) in the alkylation of adenine in solution or solid phase, and the catalytic esterification of various glycerol derivatives with fatty methyl esters at room temperature. On occasions, the action of the phosphazene bases may promote processes that other proton abstractors do not, such as the observed rearrangement of (43) to the flavone (44) in the presence of (40e) (OBn = benzoyloxy). Patented process, include the purification " and assembly of polyhedral oligomeric silsesquioxane monomers, and the catalytic activation of silylated nucleophiles. ... 

Vinyl, acryl, methacryl groups, or their derivatives were introduced to the 1-position of pyrimidine (cytosine, uracil, and thymine) or 9-position of purine (adenine, guanine, and hypoxanthine) to yield the vinyl monomers, which were polymerized with the aid of radical initiators in organic solvents... 

The template polymerization of methacrylate monomers containing nucleic acid base was studied in the presence of the template polymer containing complementary nucleic acid bases. Four monomers N-P-methacryloylethyl derivatives of adenine (MAOA), thymine (MAOT), uracil (MAOU), and theophylline (MAOThe) were synthesized. Atactic polymers were obtained from these monomers by radical polymerization initiated by azobisiso butyronitrile (AIBN) in dimethylsulfox-ide (DMSO) solution and used as templates. 

While there have been only a few papers published on 5-fluoro--uracil and/or 6-methylthiopurine based monomers, much work has been reported for uracil and adenine which could be considered the parent compounds. Much of this work has been reviewed recently and it is not necessary to repeat this here in detail (2,8,20,21). The monomers synthesized include 1-vinyluracil (22,23), 9-vinyl-adenine (22,23), l-(N-2-methacryloyloxyethyl)uracil (24,25), 9-(N-2-meth-acryloyloxyethyl)adenine (24,25), styrene derivatives of uracil (26,27) and adenine (26,27), 1-(N-vinylcarbamoyl)uracil (28) and various amino acid derivatives of uracil and adenine (29-31). 

The vinyl derivatives of uracil and adenine have been studied more extensively than the other monomers. While 1-vinyluracil was found to undergo cyclopolymerization in some initial studies (32), subsequent research was able to prepare linear polymers which were water soluble (33,34). The 9-vinyladenine monomer readily polymerized on free radical initiation to yield water soluble polymers (22,35,36). The solution properties of these systems have been studied and they form complexes with each other in a manner similar to naturally occurring nucleic acids (20,21). These polymers do exhibit some biological activity including the inhibition of murine leukemia virus (37,38) and E. coli RNA polymerase (39). 

---