Kazuya Koumoto

Gel formation properties of a uracil-appended cholesterol gelator and cooperative effects of the complementary nucleobases

Abstract We designed and synthesized a uracil-appended cholesterol gelator ( 1 ) in order to control the gel stability and the gel morphology by addition of the complementary and non-complementary nucleobase derivatives. Compound 1 forms columnar stacks in cyclohexane due to the van der Waals interaction (cholesterol–cholesterol interaction) and the intergelator hydrogen bonding between uracil moieties. Addition of a ‘monomeric’ adenosine ( 3 ) into the gel only decreases the stability with increasing the concentration. The destabilization is ascribed to a lack of intergelator hydrogen bonding accompanied with forming the complementary base pairs between 1 and 3 . In contrast, addition of adenine-appended cholesterol ( 7 ) induces a different behavior; with increasing 7 concentration the mixed gel is initially stabilized and then destabilized, giving rise to a maximum at the ratio of 1 / 7 =1:1 for the Tgel plot. One may consider, therefore, that when the additive has a common, column-forming cholesterol moiety, the cholesterol–cholesterol interaction can operate cooperatively with the complementary base pairing. In addition, the gel fiber structure is clearly changed by the addition of 7 . Taking the fact that there is no report for such an additive effect inducing a structural change with maintaining the gel stability into consideration, our attempt combining cholesterol columnar stacks with the nucleobase additives provides a new methodology to control the stability and the morphology of organogels.

Sol–gel phase transition induced by fiber–vesicle structural changes in sugar-based bolaamphiphiles

The research objects of this paper were to design bolaamphiphilic gelators utilizing a sugar family as a source of solvophilic groups and an azobenzene segment as a solvophobic group and to monitor the aggregation mode utilizing the spectroscopic properties of the azobenzene chromophore. The results indicated that the bolaamphiphiles act, although only for specific DMSO–water mixtures, as gelators and form a unique supramolecular helical structure in the gel phase. The UV-Vis and CD spectra showed that the azobenzene segments adopt H-type face-to-face orientation and the dipole moments are arranged in the right-handed (R)-helicity. Since the fibrils as observed by electron microscope possess the right-handed helical structure, one may consider that the microscopic azobenzene–azobenzene orientation is reflected by the macroscopic supramolecular structure. When boronic acid-appended poly(L-lysine) was added, the gel phase was changed into the sol phase in the macroscopic level and the fibrous aggregate was changed into the vesicular aggregate in the microscopic level. These changes, which are usually induced by a temperature change, are due to the specific boronic acid–sugar interaction occurring at the constant temperature. Interestingly, when D-fructose which shows high affinity with the boronic acid group was added, the sol phase and the vesicular aggregate were changed back to the gel phase and the fibrous aggregate, respectively. This means that the phase and morphological changes in the sugar-integrated bolaamphiphiles can be controlled reversibly.

Efficient glucoside extraction mediated by a boronic acid with an intramolecular quaternary ammonium ion

Abstract To develop an efficient sugar extractant on the basis of the mechanistic view a phenylboronic acid bearing a trioctylammonium group at the ortho position ( 4 ) was synthesized. To avoid the complexity we employed a simple two-phase solvent-extraction system which corresponds to the first step in membrane transport, i.e. , extraction from a donating aqueous phase to an organic liquid membrane phase. The extraction rates and equilibria were estimated using α - p -nitrophenyl-D-glucopyranoside as a sugar and 1,2-dichloroethane as an organic phase and compared with those of a 2-methylphenylboronic acid ( 5 ) / trioctylmethylammonium chloride (TOMAC) 1:1 binary system. The extraction rates for 4 were faster by 2.5 – 29 fold than those for 5 + TOMAC. The distribution coefficients were also enhanced by 5 – 8 fold. The results indicate that the intramolecular quaternary ammonium group is very effective to neutralize the anionic charge developed in the boron atom upon sugar-binding and create extractable zwitterionic sugar complexes.

Schizophyllans carrying oligosaccharide appendages as potential candidates for cell-targeted antisense carrier.

Schizophyllans carrying beta-lactoside and alpha-mannoside appendages were prepared from native schizophyllan through NaIO4 oxidation followed by reductive amination using aminoethyl-beta-lactoside and alpha-mannoside, respectively. The resulting schizophyllans form stable macromolecular complexes with polynucleotides, such as poly(C) and poly(dA). Specific affinity between these macromolecular complexes and saccharide-binding proteins was demonstrated by surface plasmon resonance and agarose gel staining assays. beta-lactoside-appended schizophyllan enhanced an antisense activity in hepatocytes which express lactoside-binding proteins on their cell surfaces.

Design of a Visualized Sugar Sensing System Utilizing a Boronic Acid-azopyridine Interaction

Abstract The boronic acid-amine (B-N) interaction was applied to the molecular design of a visualized sensing system for saccharides. 3-Nitrophenyl-boronic acid (3b) interacts with the pyridine nitrogen of 4-(4-dimethyl-aminophenyl-azo) pyridine (2) in methanol and changes its color from yellow to orange. Added saccharides form complexes with 3b and enhance the acidity of the boronic acid group. As a result, the B-N interaction becomes stronger and the intensified intramolecular charge-transfer band changes the solution color to red. By combined 1H-NMR and absorption spectroscopic studies, four association constants governing the present ternary complex system have been determined. In case of D-fructose, the 3b·D-fructose complex can interact with 2 240 times more strongly than 3b and the 2·3b complex can associate D-fructose 241 times more strongly than 3b. Clearly, the B-N interaction not only enables the colorimetric saccharide sensing but also enhances the association ability (i.e., sensitivity). Thus...

Lactose-appended schizophyllan is a potential candidate as a hepatocyte-targeted antisense carrier.

A schizophyllan (beta-1,3-glucan) derivative carrying lactose-appendages prepared by reductive amination can form stable macromolecular complexes with polynucleotides, shows excellent affinity with a lactose-binding lectin, and effectively mediates gene transfection into hepatocytes.

TEM and SEM observations of super-structures constructed in organogel systems from a combination of boronic-acid-appended bola-amphiphiles with chiral diols

Two bola-amphiphilic α,ω-diboronic acids separated by a (CH2)11 or (CH2)12 group were synthesized. Complexation with chiral diols readily gave new amphiphiles end-capped with the chiral substituents. Some of these acted as good gelators of organic solvents. Transmission electron microscope and scanning electron microscope observations established that a variety of super-structures are created in the organogels, depending on the solvents and the structure of the chiral end-cap groups. In most cases, the fibrous aggregates, the network structure which is the driving-force for gelation, showed a helical higher-order structure reflecting the chirality of the end-cap groups. The results indicate that the combinatorial approach utilizing boronic acid functions and diol compounds is useful in creating a variety of new super-structures in the gel phase.

Polysaccharide-polynucleotide complexes. Part 7. Hydrogen-ion and salt concentration dependence of complexation between schizophyllan and single-stranded homo RNAs

Schizophyllan belongs to a beta-1,3-D-glucan family, which exists as a random coil in dimethyl sulfoxide (DMSO) and as a triple helix in water, respectively. The schizophyllan single chain forms a complex with single-stranded homo RNAs in water/DMSO mixed solvents. Using circular dichroism, we studied the complexation and its stability as a function of apparent pH (pH(*)) in a mixed solvent system and as a function of the salt concentration. The complex is formed in the pH(*) range 6.5-10, and dissociated in the pH(*) range 4-6. Both poly(A) and poly(C) adopt a double strand in the pH(*) range 4-6 and a single strand in the pH(*) range 6.5-10. Therefore, the conformational change of each polynucleotide is responsible for dissociation/association of the complex, i.e., the single strand of the polynucleotides can form complexes, whereas the double one cannot. This result indicates that hydrogen bonding and similarity of the helix parameters are essential for the complex formation. The melting temperature of the complex reaches the maximum around 0.05 M of NaCl and KCl, and the value of the maximum temperature depends on the cation species.

SUPER-STRUCTURES CAN BE CONSTRUCTED IN ORGANOGELS FROM COMBINATION OF A BORONIC-ACID-APPENDED BOLAAMPHIPHILE WITH CHIRAL DIOLS

Abstract A bolaamphiphile bearing two boronic acid groups at the two ends was synthesized. Complexation with chiral diols readily afforded new amphiphiles end-capped with the chiral substituents. Some of them acted as gelators of organic solvents. TEM and SEM observations established that a variety of super-structures are created in the organogels, depending on the solvents and the structure of the end-cap groups.

Polysaccharide–polynucleotide complexes (15): thermal stability of schizophyllan (SPG)/poly(C) triple strands is controllable by α-amino acid modification

Schizophyllan (SPG), a beta-1,3-glucan polysaccharide which is known to form macromolecular complexes with certain polynucleotides, was modified by a reductive amination method with alpha-amino acids (Arg, Lys, and Ser). The thermal stability of the complexes as estimated by T(m) was enhanced in SPG-Arg and SPG-Lys conjugates which have pI values higher than the pH of the medium (8.0). The T(m) shift increased with the increase in the percentage of alpha-amino acid introduced and the highest T(m) values attained were 64 degrees C for SPG-Arg conjugate and 62 degrees C for SPG-Lys conjugate, which are higher by 13 and 11 degrees C, respectively, than those of the unmodified SPG+poly(C) complex. In the SPG-Ser conjugate with a pI lower than the medium pH (8.0), the T(m) values decreased with an increase in the percentage of Ser. Formation of the macromolecular complex was no longer detected above 13.2% Ser. The findings indicate that the T(m) values are easily controllable by the type and percentage of the introduced alpha-amino acids. We believe, therefore, that the present conjugates, consisting of naturally originated SPG and alpha-amino acids, provide an important lead for developing nontoxic artificial vectors and to control the affinity with polynucleotides in response to medium pH and temperature.