To develop the radical polyaddition of bisperfluoroisopropenyl esters, the reactions of bis(α‐trifluoromethyl‐β,β‐difluorovinyl) terephthalate [CF2C(CF3)OCOC6H4COOC(CF3)CF2] (BFP) with dialkoxydialkylsilane were examined to prepare fluorinated hybrid polymers bearing dialkylsilyl groups in the main chain. Prior to polyaddition, the radical addition reaction of 2‐benzoyloxypentafluoropropene [CF2C(CF3)OCOC6H5] (BPFP) has been investigated to afford the results that diethoxydimethylsilane (DEOMS) or dimethoxydimethylsilane with BPFP initiated by oxo radical are the best combination for the preparation of polymers. The mechanism of the addition reaction was proposed. Radical polyaddition of BFP with DEOMS initiated by benzoyl peroxide or di‐tert‐butyl peroxide has yielded polymers of up to molecular weight 1 × 106 with rather broad molecular weight distribution. A mechanism for the polyaddition reaction is proposed based on the radical addition reaction between BPFP and DEOMS. The step‐growth polymerization is initiated by hydrogen abstraction of DEOMS to add a perfluoroisopropenyl group, followed by a 1,7‐shift of the radical in the intermediate. The relationship between addition reaction mechanism and polyaddition mechanism was also discussed.

An N-methylguanidine-bridged nucleic acid (GuNA[NMe]), a guanidine-bridged nucleic acid (GuNA) bearing a methyl substituent at the bridge, was successfully synthesised and incorporated into oligonucleotides. By employing an acetyl protecting group, GuNA[NMe]-modified oligonucleotides bearing acid-sensitive purine nucleobases were successfully prepared. The obtained GuNA[NMe]-modified oligonucleotides exhibit excellent binding affinity towards the complementary single-stranded RNA and DNA. Furthermore, even a single GuNA[NMe] modification provides robust enzymatic stability, similar to that achieved by the well-established phosphorothioate backbone modification. These data indicate that such a GuNA[NMe] represents a valuable modification for the development of therapeutic oligonucleotides.

We recently designed guanidine-bridged nucleic acids (GuNA), and GuNA bearing a thymine (T) nucleobase was synthesized and successfully incorporateed into oligonucleotides. The GuNA-T-modified oligonucleotides possessed high duplex-forming ability towards their...

Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH-π, lone pair (LP)-π, and π-π interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.Some types of nucleic acid modifications such as methylation and acetylation are known to directly affect the functions of DNA and RNA. These modifications play a critical role in DNA manipulation and can considerably affect DNA transcription and replication 1-4 . In addition, artificially modified nucleic acid molecules with halogen atoms, such as 5-fluorouracil (5FU) and trifluorothymidine (FTD), have been used in medical science and for clinical therapies 5-9 . The 5FU acts as an antitumor drug by inhibiting the formation of ribosomal RNA by its incorporation into RNA replacing uracil, or inhibiting DNA synthesis by preventing thymidylic acid synthesis 10-12 . Recent studies have shown that 5FU also gets incorporated into DNA, however, the association between this incorporation and the antitumor effects remains unknown. Conversely, FTD, which is incorporated with DNA, possesses a highly effective antitumor potency 13-15 although its structure is similar to that of thymidine. The combination of FTD and tipiracil hydrochloride (FTD/TPI) has been approved by some organizations, such as the FDA (Food and Drug Administration of the United States), as a treatment for colorectal cancer 16 . The reason why FTD has antitumor effect is not known yet, although many studies about it have been reported [17][18][19][20][21][22] . It is said today that the reason is not to form a covalent bond with thymidylate synthase 17 but to lead to DNA dysfunction by the incorporation of FTD into DNA from s...