Misaki Nakai

Integrated Palladium-Catalyzed Arylation of Heavier Group 14 Hydrides

A convenient procedure has been developed for the preparation of Group 14 compounds by integrated palladium-catalyzed cross-coupling of aromatic iodides with the corresponding Group 14 hydrides in the presence of a base. The reaction conditions can be applied to the cross-coupling of tertiary, secondary, and primary Group 14 compounds. In most cases, the desired arylated products were obtained in synthetically useful yields. Even in the case of aryl iodides containing OH, NH(2), CN, or CO(2)R groups, the reactions proceeded with good to high yields with tolerance of these reactive functional groups. A possible application of this method is the unique synthesis of a fungicidal diarylmethyl(1H-1,2,4-triazol-1-ylmethyl)silane derivative.

Syntheses, Characterization, and Antitumor Activities of Platinum(II) and Palladium(II) Complexes with Sugar-Conjugated Triazole Ligands

Four platinum(II) and palladium(II) complexes with sugar‐conjugated bipyridine‐type triazole ligands, [PtIICl2(AcGlc‐pyta)] (3), [PdIICl2(AcGlc‐pyta)] (4), [PtIICl2(Glc‐pyta)] (5), and [PdIICl2(Glc‐pyta)] (6), were prepared and characterized by mass spectrometry, elemental analysis, 1H‐ and 13C‐NMR, IR as well as UV/VIS spectroscopy, where AcGlc‐pyta and Glc‐pyta denote 2‐[4‐(pyridin‐2‐yl)‐1H‐1,2,3‐triazol‐1‐yl]ethyl 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranoside (1) and 2‐[4‐(pyridin‐2‐yl)‐1H‐1,2,3‐triazol‐1‐yl]ethyl β‐D‐glucopyranoside (2), respectively. The solid‐state structure of complex 6 was determined by single‐crystal X‐ray‐diffraction analysis. These complexes exhibited in vitro cytotoxicity against human cervix tumor cells (HeLa) though weaker than that of cisplatin.

Observation of electrochemical single-electron-transfer events of gold nanoparticles in aqueous solution in the presence of both ammonium and sulfonate surface-active agents.

Metal nanoparticles (MNPs) behave as quantum dots and have attracted much attention in the fields of molecular electronics, catalysis, 3] and sensors. 4] Recently, biomaterials chemistry has employed MNPs intensively, and MNPattached proteins and DNAs have been used as DNA sensors, immunosensors, sugar sensors, HIV drugs, and photosensors, and thus the importance of the physical and chemical properties of MNPs in aqueous solution is increasing. It is known that MNPs smaller than 2.0 nm in diameter have a capacitance CCLU of less than one attofarad (1 aF) per nanoparticle in electrolyte solution, which enables observation of single-electron-transfer events even at room temperature. This phenomenon is called quantized double-layer (QDL) charging, and CCLU is given by Equation (1), where e is

Synthesis and photodynamic properties of maltohexaose-conjugated porphyrins

A series of porphyrin derivatives with one to four maltohexaose moieties in their meso positions have been synthesized. Zinc or free-base m-THPP (5,10,15,20-tetrakis(m-hydroxyphenyl)-porphyrin) was used as the porphyrin platform. The reaction of m-THPP with 3-iodopropyl nonadecaacetylmaltohexaoside afforded a mixture of all possible combinations of glycoconjugated porphyrins having one to four maltohexaose moieties; monoglycosylated (Ac-1), bisglycosylated (Ac-cis-2 and Ac-trans-2), triglycosylated (Ac-3), and tetraglycosylated (Ac-4) porphyrins were obtained in 11–26% yield. Removal of acetyl groups at maltohexaose moiety afforded highly water-soluble glycoconjugated porphyrins 1–4. Zinc derivatives were synthesized in a similar manner. These maltohexaose-linked porphyrins exhibit remarkable water-solublity (530 mg/mL for 4). The singlet oxygen production ability upon visible light irradiation is not affected by the maltohexaose substitution. Photo- and dark cytotoxicities of the maltohexaose-conjugated porphyrins 1–4 and Zn-1–4 were examined against a HeLa cell line, which showed that the mono-maltohexaosylated derivative (1 and Zn-1) was the most effective photosensitizer for PDT.

DNA Interaction and Cytotoxicity of Cyclometalated Ruthenium(II) Complexes as Potential Anticancer Drugs

To evaluate the anticancer activity of the cyclometalated ruthenium(II) complexes [Ru(bpy)2(C^N)]Cl, we have studied the interaction of these complexes using calf thymus DNA (CT-DNA) and cytotoxicity assays with two tumor (L1210 and HeLa) and a non-tumor (BALB/3T3 clone A31) cell lines. It is suggested that the complexes act as intercalators and/or DNA minor groove binders. Moreover, the complexes display favorable cytotoxicity activities with L1210 and HeLa, which in all cases were significantly more favorable than cisplatin. In contrast, the complexes exhibit appreciably lower cytotoxicity toward BALB/3T3 clone A31.

Syntheses and photodynamic properties of glucopyranoside-conjugated indium(III) porphyrins as a bifunctional agent

The glucopyranoside-conjugated porphyrins, H2TPP{p-O-(CH2)2-O-OAcGlc} (1), [InTPP{p-O-(CH2)2-O-OAcGlc}]NO3 (2), H2TPP{p-O-(CH2)2-O-Glc} (3), [InTPP{p-O-(CH2)2-O-Glc]-NO3 (4) and ZnTPP{p-O-(CH2)2-O-OAcGlc} (5) were synthesized, and characterized by 1H NMR, 13C NMR, ESI-MS, UV-vis spectroscopies and elemental analyses. In the 1H NMR spectrum of 2, two sets of signals were observed for H-atoms of the phenyl group of porphyrin, indicating that 2 has the axial chirality due to a NO3 ion coordinating to the indium atom. Abilities of the singlet oxygen production of these porphyrins, investigated by using 1,3-diphenylisobenzofuran (DPBF) as a quencher, were higher than those of the free-based and zinc porphyrins, reflecting the heavy atom effect. The photodynamic properties of these porphyrin derivatives were investigated against COLO 679. All of the glucopyranoside-conjugated porphyrins exhibited the high photocytotoxicity compared with Laserphyrin®. Above all, 4 exhibited the highest photocytotoxicity, coinciding with the high abilities of this complex for the singlet oxygen production and the cell permeability.

Synthesis of Glucopyranosyl Schiff Base Zinc(II) Complexes Capable of Interacting with Mononucleotides, and Their DNA-Cleavage Activities

New glucopyranosyl Schiff base zinc complexes, [Zn(GlcSal)2] (1; GlcSalH=N‐(2‐deoxy‐β‐D‐glucopyranos‐2‐yl‐salicylaldimine) and [Zn(AcOGlcSal)2] (2; AcOGlcSalH=N‐(2‐deoxy‐β‐D‐1,3,4,6‐tetraacetylglucopyranos‐2‐yl‐salicylaldimine) were synthesized, and characterized by spectral and analytical methods. The interaction between the Zn complexes and mononucleotides was investigated by 1H‐NMR, 31P‐NMR and UV/VIS spectroscopies. Mononucleotides, cytidine 5′‐monophosphate (CMP) and uridyl 5′‐monophosphate (UMP), interacted with these complexes to form a 1 : 1 complex with 1 and a 1 : 2 complex with 2, depending on the presence of the OH group of glucopyranosyl substituents. The DNA‐cleavage activities of 1 and 2 were studied using plasmid DNA (pBR322) in a medium of 5 mM Tris⋅HCl/50 mM NaCl buffer in the presence of H2O2. The DNA‐cleavage activity decreased in the order of 2>1>Zn(OAc)2, indicating the significant promoting effect of the glucopyranosyl Schiff base ligand and the participation of the glucopyranosyl OH groups in the cleavage mechanism. The mechanism of the DNA cleavage by 1 and 2 was investigated by evaluation of the effect of a HO. radical scavenger and a singlet‐oxygen (1O2) quencher under aerobic conditions. The former exhibited little effect, excluding the HO. radical as an active species and supporting the hydrolysis mechanism for the main process of the DNA cleavage. The latter quencher somewhat hindered the cleavage, indicating the partial participation of a 1O2 as a competitive active species in the present system.

Evaluation of 99m Tc-sulfonamide and sulfocoumarin derivatives for imaging carbonic anhydrase IX expression

With the aim to prepare hypoxia tumor imaging agents, technetium(I) and rhenium(I) tricarbonyl complexes with dipyridylamine (L1 = N-{[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinylmethyl)-2-pyridinemethanamine; L3 = N-{[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinyl-methyl)-2-pyridinemethanamine), and iminodiacetate (H2L2 = N-{[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazole-4-yl]methyl}-N-(carboxy-methyl)-glycine; H2L4 = N-{[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazole-4-yl]methyl}-N-(carboxymethyl)-glycine) ligands appended to sulfonamide or sulfocoumarin carbonic anhydrase inhibitors were synthesized. The Re(I) complexes were characterized using 1H/13C NMR, MS, EA, and in one case the X-ray structure of [Et3NH][Re(CO)3(L2)] was obtained. As expected, the Re coordination geometry is distorted octahedral, with a tridentate iminodiacetate ligand in a fac arrangement dictated by the three strong-field CO ligands. Inhibition studies of human carbonic anhydrases (hCAs) showed that the Re sulfocoumarin derivatives were inactive against hCA-I, -II and -IV, but had moderate affinity for hCA-IX. The Re sulfonamides showed improved affinity against all tested hCAs, with [Re(CO)3(L4)]- being the most active and selective for the hCA-IX isoform. The corresponding 99mTc complexes were synthesized from fac-[99mTc(CO)3(H2O)3]+, purified by HPLC, and obtained with average 41-76% decay-corrected radiochemical yields and with >99% radiochemical purity. Uptake in HT-29 tumors at 1 h post-injection was highest for [99mTc(CO)3(L4)]- (0.14 ± 0.10%ID/g) in comparison to [99mTc(CO)3(L1)]+ (0.06 ± 0.01%ID/g), [99mTc(CO)3(L2)]- (0.03 ± 0.00%ID/g), and [99mTc(CO)3(L3)]+ (0.07 ± 0.03%ID/g). The uptake in tumors was further reduced at 4 h post-injection. For potential imaging application with single photon emission computed tomography, further optimization is needed to improve the affinity to hCA-IX and uptake in hCA-IX expressing tumors.