Functional monomers and polymers. CII. Synthesis and properties of oligomer models of polyethyleneimine derivatives containing pendant adenine bases

A series of oligomer model compounds of polyethyleneimine derivatives with pendant adenine bases were prepared by the reaction of a carboxyethyl derivative of adenine with oligomeric amines, using an activated ester method. To evaluate the intramolecular interaction between pendant adenine bases in these compounds, ultraviolet spectra at various pH regions were measured. Ultraviolet hypochromicities and pK_a values depended linearly on the chain length of the oligomers. The results showed that the intramolecular interactions of adenine bases were realized less in their protonated than neutral forms.     

Functional monomers and polymers. XCIV. Photochemical reactions on the synthetic polymers containing thymine bases in the presence of adenine derivatives

Photodimerization reactions of polyacrylate and polymethacrylate derivatives and the dimer model compound containing thymine bases were studied in the presence of adenine derivatives in dimethyl sulfoxide; N,N-dimethylformamide; and dimethyl sulfoxide–ethylene glycol solutions. The photodimerization of thymine bases both in the polymers and in the dimer model compound was found to be quenched by the addition of adenine derivatives. Base-base interaction in the ground state was also studied by ultraviolet (UV) spectroscopy in the three solvents. The quenching of the photodimerizationof thymine bases in the presence of adenine derivatives was discussed in terms of the specific interaction between adenine and thymine bases both in ground and excited states.     

Interaction Between DNA and Some Salicylic Acid Derivatives and Characterization of Their DNA Targets

A nanofiber polypyrrole (PPy) film was electrochemically deposited on a Pt electrode and used for immobilization of single‐stranded DNA (ssDNA) and investigation of hybridization events. Then, the interaction of DNA with four salicylic acid (SA) derivatives was studied with electrochemical methods. The oxidation peak of guanine was decreased by increasing the concentrations of salicylic acid derivatives. The binding constants of these compounds with four different sequences of DNA including different percentages of guanine‐cytosine and adenine‐thymine bases were calculated and it was clarified that sequences with higher percentage of adenine‐thymine bases have a higher binding constant in their interaction with SA derivatives.     

Intra- and intermolecular interactions in the series of acyclic and macrocyclic compounds containing nucleotide bases and their derivatives

Intra-and intermolecular interactions in acyclic compounds containing nucleotide base (uracil and thymine) derivatives and their macrocyclic analogs (pyrimidinophanes) were studied by IR, UV, luminescence, and NMR spectroscopy. Molecules of these compounds include one or two N³-methylsubstituted or N³-unsubstituted uracil fragment or two adenine fragments linked through a hexamethylene spacer to an uracil, 5,5′-methylenediuracil or diphenylmethane fragment. The examined compounds almost all are characterized by π-π interactions and intramolecular hydrogen bonding between the terminal uracil or adenine fragments. Intramolecular association constants were determined and factors affecting them were discussed. Complex formation of acyclic and macrocyclic ligands with adenine and thymine derivatives was studied. The low values of the association constants were interpreted in terms of a competition between intra-and intermolecular bonding and very labile ligand structure.     

Functional monomers and polymers. CXVII. Photochemical reactions on oligo- and polyethyleneimines containing pendant thymine bases: Effect of the spacer

The photodimerization reaction of thymine bases incorporated in the modified oligo- and polyethyleneimines, in which α-alanine or ß-alanine unit was inserted between the main chain and the pendant thymine bases, was studied both in aqueous and in dimethyl sulfoxide solutions. It was found that the quantum yields for the photodimerization for the oligomers were closely related to the intramolecular interaction in the ground state, while those of the copolymers were not related to the ground state interaction. It was suggested that the singlet energy migration was present in the case of the polyethyleneimine derivatives. This result is discussed in terms of the effects of the nearest-neighboring thymine units, the structure of the side chain, and the singlet energy migration, particularly for the copolymers.     

Functional monomers and polymers. XXXXVII. Complex formation of stereoregular methacryloyl-type polymers containing nucleic acid bases

The complex formation between a poly(N-β-methacryloyloxyethyl) derivative of adenine with one of thymine or uracil was studied in dimethyl sulfoxide and ethylene glycol mixture by ultraviolet (UV) spectroscopy. For the polymer pairs containing complementary nucleic acid bases both hypochromicity and hyperchromicity were found. Stereoregularity of the polymers, as well as the conditions for measurement of, for example, solvent, temperature, and time, affected the complex formation. Both inter- and intramolecular interaction of polymers in solution were discussed in some detail.     

Functional monomers and polymers. XCVII. Synthesis of oligomer models of polyethyleneimine derivatives containing pendant thymine bases

A series of oligomer models of polyethyleneimine derivatives having pendant thymine bases were prepared by the reaction of carboxyethyl derivatives of thymine with oligomer amines using an activated-ester method. It was found that the hypochromicity values obtained from UV spectra and pKa values obtained from spectrophotometric titrations depend on the chain length of the oligomers and the thymine content of the polymers.     

Vinylsulfonylethyl derivatives of nucleic acid bases and their graft polymers on polyethyleneimine

Vinylsulfonylethyl (VSE) derivatives of the nucleic acid bases adenine, thymine, cytosine, and the nucleosides inosine and uridine have been prepared via a simple Michael reaction with divinyl sulfone. The VSE derivatives were grafted on a polyethyleneimine (PEI) backbone. PEI of different molecular weights (1400, 1800 and 50,000–100,000) were used and also two different molar ratios (1:1 and 1:2) of monomer to PEI were employed. From the ¹H-NMR and elemental analysis, it appeared that in almost all instances the grafting was quantitative. In one case, both 1-VSE-thymine and 9-VSE-adenine were grafted on the same PEI backbone. Interactions between some of these polymers were investigated by UV spectroscopy. The expected complementary base pairing was observed only in DMSO–ethylene glycol solvent system but not in DMSO. The adenine polymer showed a one-to-one interaction with the thymine polymer.     

Functional monomers and polymers. CLIV. Application of nucleic acid base containing polymers to high performance liquid chromatography

Poly-L -lysine (PLL) derivatives containing pendant nucleic acid base, such as thymine or adenine, were bonded successfully to 3-aminopropylsilanized silica (APS-silica) and silica gel. These resins were found to be useful as the column of high performance liquid chromatography (HPLC) for the selective separation of oligoethyleneimine derivatives having pendant thymine or adenine bases.     

Transient absorption spectra and quenching of coumarin excited states by nucleic acid bases.

Triplet-triplet absorption spectra of coumarin show different profiles and maxima in ethanol from those in water, which are very similar to those reported in benzene. Long-lived transient species other than triplet states were generated as initial photoproducts between coumarins and nucleic acid bases. The excited singlet and triplet states of coumarins were quenched by nucleic acid bases. Adenine base quenched the excited singlet state of coumarins more efficiently than thymine base. However, photocycloadducts of furocoumarins are formed predominantly with thymine, and not with adenine. Moreover, it is reported that the poly[dA-dT].poly[dA-dT] sequence region is the most favourable site for the photocycloaddition reaction of furocoumarins. The results imply that adenine contributes to singlet-state photocycloaddition reaction of furocoumarins with thymine, probably through an adenine-furocoumarin-thymine termolecular interaction.     

Spectroscopic examination of linear poly(ethylenimine) containing nucleic acid pendants as polynucleotide analogs

The NMR spectra and UV absorptions of polynucleotide analogs with a poly(ethylenimine) (PEI) backbone containing adenine, cytosine, and hypoxanthine pendants have been examined. As has been shown in single-stranded polynucleotides, these polymers also exhibited base stacking behavior in aqueous solution as well as in 2,2,2-trifluoroethanol. Such stacking resulted in significant UV hypochromicities and observed differences in the NMR spectra compared to the corresponding model compounds. From continuous variation mixing experiments, well-defined base pairing interactions were observed between complementary graft polymers in aqueous solutions. Enhanced UV hypochromicity due to such interactions was also observed.     

Synthetic models related to DNA intercalating molecules: Preparation of 9-aminoacridines linked to the nucleotide bases adenine,guanine and thymine

A series of novel compounds were prepared in which the aromatic ring of the drug quinacrine (2-methoxy-6-chloro-9-alkylaminoacridine) is linked to the nucleotide bases adenine, guanine and thymine by penta-and hexamethylene bridges.     

Synthetic models related to dna-intercalating molecules a study of the ring-ring stacking interactions between 8-alkoxypsoralen and thymine.

As a contribution to the problem of the intercalation and photobinding of psoralens to DNA, model compounds were prepared in which the psoralen ring is linked to thymine by a polymethylene bridge. The ring-ring intramolecular interaction in the models was assessed by hypochromism measurement in the UV.     

INTERACTIONS AND PHOTOREACTIVITY OF 8-ALKOXYPSORALENS WITH THYMINE. A MODEL APPROACH

Abstract— To investigate the interactions and the photoreactions in solution between thymine and psoralen, model compounds have been synthesized in which a thymine molecule is linked to a psoralen ring by a polymethylene bridge. Two series of compounds have been studied and compared as models for the two major drugs 5-MOP and 8-MOP. We report here the results obtained in the 8-alkoxypso-ralen series. In water, intramolecular ring-ring stacking interactions were evidenced using UV and ¹H NMR spectroscopies. In organic solvents such as ethanol, these interactions disappear completely. The photoreactivity of the models was examined in relation to their ground state interaction properties. in water and in ethanol. Slow photolysis of the pyrone ring of psoralen occurs whatever the length of the linking chain (3 to 12 methylenes). No intramolecular thymine-psoralen photoaddition nor psoralen photodimerization were observed. These results are discussed with regards to the behavior of the 5-alkoxy models which lead selectively to the 3,4 psoralen-thymine photoadduct.     

Synthesis and Properties of Hydrophilic Copolymers Containing 5-Fluorouracil,Thymine, or Adenine

Hydrophilic copolymers containing 5-fluorouracil (5-FU), thymine, or adenine were prepared by the free-radical copolymerization of methacryloyl-type monomers containing them with water-soluble vinyl monomers such as acrylic acid, methacrylic acid, vinylpyrroli-done, acrylamide, and 4(5)-vinylimidazole with AIBN as initiator. Complex formation between the copolymers and RNA and between the copolymers having complementary nucleic acid bases in aqueous solution and a DMSO-ethylene glycol was studied by means of UV spectroscopy. These copolymers were found to release the N-hydroxyethyl derivatives of 5-FU, thymine, or adenine by hydrolysis of the ester of the polymer side chain under mild conditions. The effects of the kind of water-soluble comonomer, temperature, pH, and the imidazole group as catalyst on the hydrolysis of the ester are discussed.     

Functional monomers and polymers. CXXI. Methylation and interaction studies on adenine containing polymethacrylate derivatives

Studies of the methylation of polymethacrylate derivatives with adenine bases were made in comparison to those with uracil bases. The polymethacrylate derivatives with adenine bases were methylated by using methyl iodide in dimethyl sulfoxide solution to produce polymers that contained N¹-methyladenine and N¹, N⁶-dimethyladenine units. The products were identified by spectroscopic data and by preparing their model compounds. The methylated polymers obtained were further applied in a study of polymer complex formation with uracil-base polymers.     

Copolymers containing alternating sequences of nucleic acid base pairs. II. Polymerization studies

The objective of this project was to utilize the alternating copolymerizability of electrondonor monomers with electron-acceptor monomers to selectively introduce nucleic acid bases into copolymers in a controlled sequence distribution. To this end, maleimide monomers containing the adenine, thymine, cytosine, and 6-chloropurine moieties were converted to their hompolymers. The homopolymer of 1-(vinyloxyethoxy)thymine was also prepared. Alternating copolymers of the adenine maleimide monomer and the corresponding 6-chloropurine maleimide monomer with 1-(vinyloxyethoxy)thymine were prepared. The latter copolymer was converted to the alternating adenine–thymine copolymer by reaction with ammonia. Characterization of the polymers and copolymers via spectroscopic methods and physical measurements confirm their proposed structures. Monomer syntheses and characterization, as well as studies designed to establish the extent and nature of adenine–thymine interactions in the copolymers, are reported in accompanying papers.     

Mixed‐Valent Molecular Triple Deckers

Two phenothiazine (PTZ) moieties were connected via naphthalene spacers to a central arene to result in stacked PTZ‐arene‐PTZ structure elements. Benzene and tetramethoxybenzene units served as central arenes mediating electronic communication between the two PTZ units. Based on cyclic voltammetry, UV/Vis‐NIR absorption, EPR spectroscopy, and computational studies, the one‐electron oxidized forms of the resulting compounds behave as class II organic mixed‐valence species in which the unpaired electron is partially delocalized over both PTZ units. The barrier for intramolecular electron transfer depends on the nature of the central arene sandwiched between the two PTZ moieties. These are the first examples of rigid organic mixed‐valent triple‐decker compounds with possible electron‐transfer pathways directly across a stacked structure, and they illustrate the potential of oligo‐naphthalene building blocks for long‐range electron transfer and a future molecular electronics technology.     

Protonation studies of modified adenine and adenine nucleotides by theoretical calculations and (15)N NMR

The acid/base character of nucleobases affects phenomena such as self-association, interaction with metal ions, molecular recognition by proteins, and nucleic acid base-pairing. Therefore, the investigation of proton-transfer equilibria of natural and synthetic nucleos(t)ides is of great importance to obtain a deeper understanding of these phenomena. For this purpose, a set of ATP prototypes was investigated using (15)N NMR spectroscopy, and the corresponding adenine bases were investigated by theoretical calculations. (15)N NMR measurements provided not only acidity constants but also information on the protonation site(s) on the adenine ring and regarding the ratio of the singly protonated species in equilibrium. Substituents of different nature and position on the adenine ring did not change the preferred protonation site, which remained N1. However, for 2-thioether-ATP derivatives a mixed population of N1 and N7 singly protonated species was observed. Reduction of basicity of 0.4-1 pK(a) units relative to ATP was also observed for all evaluated ATP derivatives, except for 2-Cl-ATP, for which K(a) was ca. 10,000-fold lower. To explain the substitution-dependent variations in the experimental pK(a) values of the ATP analogues, gas-phase proton affinities (PA), Delta Delta G(hyd), and pK(a) values of the corresponding adenine bases were calculated using quantum mechanical methods. The computed PA and Delta Delta G(hyd) values successfully explained the experimental pK(a) values. A computational procedure for the prediction of accurate pK(a) values was developed using density functional theory and polarizable continuum model calculations. In this procedure, we developed a set of parameters for the polarizable continuum model that was fitted to reproduce experimental pK(a) values of nitrogen heterocycles. This method is proposed for the prediction of pK(a) values and protonation site(s) of purine analogues that have not been synthesized or analyzed.     

Functional monomers and polymers. XXXXVI. A copolymerization study of methacryloyl-type monomers containing nucleic acid bases in chloroform solution

Behavior of the free radical copolymerization of N-β-methacryloyloxyethyl derivatives of adenine with that of thymine was studied in chloroform solution, taking account of the specific base-base interaction of these monomers. Hydrogen bonding interaction between such monomers was observed by NMR spectroscopy. The acceleration of copolymerization was found to be greater either at lower monomer concentration or at lower polymerization temperature. When N-β-methacryloyloxyethylcarbazole was used as a comonomer, the rate of copolymerization showed a similar trend as in the case of usual free radical copolymerizations. From r₁ and r₂ values obtained, the copolymerization was found to be alternating, particularly in the case of copolymerization between monomers having complementary nucleic acid bases. The results suggest that the hydrogen bonding interaction between adenine and thymine plays a role in the propagation step.