I : N : LW = I 2 (2I 1) N (0.37%), 19 F (100%), 29 Si (4.7%), 31 P (100%) 77. Se (7.58%), 111 Cd (12.75%), 119 Sn (8.58%) 125

Transcription

1 MR MR H C MR ( ) ( ) S = I(I+)ν 0 ( C ) R = ( C ) R = I ( I + ) ( + ) I ( I + ) ( + ) I : ν 0 : : ν 0 νc ν 0 νc α 0 αc (IET ) (line width factor) LW = (I + )Q I (I ) (0/06/06) I : Q : I=/ (0.7%), 9 F (00%), 9 Si (4.7%), (00%) 77 Se (7.8%), Cd (.7%), 9 Sn (8.8%) Te (6.99%), 9 t (.8%), 07 b (.6%) I=/ H (I =, 0.0%), 7 Li (I = /, 9.6%) B (I = /, 8.%), 4 (I =, 99.6%) 7 O (I = /, 0.07%) 0 Rh (I = /, 00%) 07 Ag (I = /,.8%), 09 Ag (I = /, 48.8%) MR,, ISB:

2 MR ΔE = hν ν = γ B 0 π γ ( H 00 MHz ) H ~ ppm C ~ 00 ppm B ~ 0 ppm ~ 40 ppm 77 Se ~ 000 ppm 9 t ~ 6700 ppm 9 Co ~ 8000 ppm H (= 9 F H ) ( ) high frequency low frequency

3 MR H MR H, I =, 0.0%, γ = =.8 0, = Si(CD ) 4 = 0 H MR styrene-d 8 8 MeReO H MR spectrum (C 6 D 6 ) H MR spectrum (C 6 D 6 ) J. Mol. Cat. B: Enzymatic 0, 7, 7. Chem. Commun. 00, 66.

4 MR 7 Li, 6 Li MR 7 Li, I = /, 9.6%, γ = 0.96 LiCl/D = 4 0, =.4 0 O = 0 0~ ppm 6 Li, I =, 7.4%, γ =.97 = 8 0 4, =.8 7 Li vs. 6 Li 7 Li Me Si RI(rapid injection)mr 6 Li (h 6 Li) (h 6 Li) 4 Et O 6 Li C MR rof. Hans J. Reich@U Wisconsin J. Am. Chem. Soc. 007, 9, 49. J. Am. Chem. Soc. 998, 0, 70. 4

5 MR B MR B, I = /, 80.4%, γ = BF OEt = 0 = 4. 0, = ~90 ppm (0~90 ppm) vs. ( 0~0 ppm) BBr : 8. ppm, BBr pyridine: 7. ppm B MR B MR B Energy Environ. Sci. 009,, δ B 9 Science 0, 6, 40. δ B 47 Science 006, 4,. Et Et δ B 7 δ B 0 Science 00, 8, 4. t δ B. Science 0,, 60. B B Dur Dur at. Chem. 0,,.

6 多核MR各論 MRスペクトル, 核スピンI = /, 天然存在比0.7%, 磁気回転比γ =.76 化学シフト基準はCHO = 0 四極子モーメント = なし, 相対総合感度 =.9 0 範囲は約 600~600 ppm アミノ酸の構成元素であるため 生体材料の解析に非常に有用 最近の応用例 窒素分子錯体の同定 Cl Mo Cl + + a!hg H- HSQC THF (6 equiv) ( atm) Cl room temp. h t = Bu {H} Mo Mo α β δ 9.0 J yield Hz, terminal α) (dt, J&6% = 6.&.4 δ 6. (d, J = 6. Hz, terminal β) δ 8. H), (s, bridging ) MR (THF-d8): " 94.6 (s). H MR (THF-d ): " 7.07 (t, J = 7. Hz, ArH, 8 全体をC,で標識した at. Chem. 0,, (d, J = 7. Hz, ArH, H), タンパクのアミノ酸配列を 直接決定可能.7 (br, CHtBu, 4H),.8 (pseudo t, CHtBu, 6H). IR (KBr, cm!): 96 (#). Raman (THF, cm!): 890 (#). 6 cf. (gas): cm!

7 多核MR各論 9F The potential clinical applicability of TAET-CD/-FC involves not only i.tu. application but also the systemic delivery of the enzyme/ prodrug system. Intratumoural production of -FU following i.v. injection of TAET-CD and i.p. injection of -FC (00 mg/kg) was measured in vivo in the HCT6 colon tumour (Figure A). The FC concentration in the tumours following i.p. injection was comparable to the i.tu. administration (-4 mm). A clear conversion of -FC to -FU was seen with this systemic application of TAET-CD/-FC, although the -FU signals were less than with the i.tu. delivery route (compare Figure and Figure A). Because of the reduced -FU signal, the conversion quality was further analysed and confirmed with in vitro high resolution 9F MRS (8.4 Tesla) of extract preparations from these tumours. Intratumoural concentrations of -FU were about mm (n ¼ 6) for the i.tu. and mm (n ¼ 7) for the systemically TAET-CD plus -FC treated tumours respectively. A representative example of this analysis (Figure B) illustrates the efficacy of the TAET-CD/-FC conversion to -FU in this i.v./i.p. administration modality. Within the total in vivo experimental time, no metabolic activity was observed in the tumours, ie, the concentrations of the catabolites and anabolites of -FU were below the detection threshold of the in vivo 9F MRS. Using the much more sensitive in vitro MRS on tumour extracts, we observed a small catabolite signal around!7 p.p.m. (i.tu mm (n ¼ 4), i.p mm (n ¼ )) and in some cases also a very small anabolite signal between. and. p.p.m. (B0.0 mm) (an example is shown in Figure 4). Those tumours, which were not further investigated with in vitro MRS, were analysed for bacterial colonization. Levels of # 087 # 08 cfu per gram tissue were found. MRスペクトル 9, 核スピンI = /, 天然存在比00%, 磁気回転比γ =.8 化学シフト基準はCFCl = 0 四極子モーメント = なし, 相対総合感度 = 範囲は約 00~900 ppm 全ての核の中でHに次いで高感度 使用例 含フッ素ポリマーの構造解析 二次元9F MR CFH三重共鳴プローブが必要 9Fのつながりを可視化可能 4 Chem Figure 4 In vitro 9F MRS WALTZ-6 decoupling) of the shown in Figure, snap-froze large conversion of -FC to -F between in vivo 9F MRS (B4 p.p.m.) and catabolite sign -FC 最近の応用例 ネズミの腫瘍に F-cytosineを注射 そのままF-uracilを検出 B A It is obviously important to evaluate normal tissue in parallel with tumour tissue, as both ultimately determine the therapeutic window of treatment. Besides the perchloric acid extracts of A -FU -FU Chemical shift (ppm) Chemic tumours, also extracts of with in vitro 9F MRS. In a detected in the tumour ( catabolite signals of a-fluo!7. p.p.m. and a-fluoroobserved in the liver extrac to -FU that was observed i -FC application was stron catabolite levels in the liv ( mm (n ¼ )) ( mm (n ¼ 6)). -FC -FC 4 Figure In vitro 9F MRS spe 6 decoupling) of the perchlo liver of a mouse (Figure ) tr injected i.tu. with -FC on day vivo evaluation (ie, about 4 h aft a mouse treated i.v. with TA snap-frozen immediately after -FC administration). In vitro 9F MRS of liver CA extracts of mice treated with TAET-CD/-FC B 0 - DISCUSSIO Chemical shift (ppm) 0 Figure (A) In vivo 9F MRS spectrum obtained after weeks (0 min/ spectrum; TR ¼ 0.7 s; S 6) of a mouse treated an i.v. injection Brit. J.¼Cancer 004, 89,with 796. of the TAET-CD system (day 0) followed with an i.p. -FC injection (00 mg/kg). Spectrum obtained. h after -FC inoculation. (B) In vitro 9F MRS spectra of the perchloric acid extract of the whole tumour from the mouse in Figure A, snap-frozen immediately after the in vivo evaluation (TR ¼. s; A ¼ 8; H decoupling). 7 In the present 9F MRS st detection of the dynamic human HCT6 colon tum cytosine deaminase- (CD (TAET-CD). The results s to -FU within 0 min w measurement time extend injection. This suggests tha of -FU is greater than the

8 多核MR各論 9Si MRスペクトル 9Si, 核スピンI = /, 天然存在比4.7%, 磁気回転比γ =.90 化学シフト基準はSiMe = 0 四極子モーメント = なし, 相対総合感度 = 範囲は約 00~00 ppm 使用例 固体 Si MRによる Al,Si含有ゼオライトの分析 最近の例 特殊な環境の Si核を含む化合物 Downloaded from on June 4, with a Si"Si double bond, tetramesityldisilene (9), and Brook et al. synthesized a compound with a Si"C double bond (0). The reaction of,,,-tetrabromo-,,4,4-tetrakis[bis(trimethylsilyl)methyl]as for triple bonds, ower and co-workers,4-diisopropyltetrasilane with four equivalents of potassium graphite (KC8) in recently prepared alkyne analogs of the tetrahydrofuran produces,,4,4-tetrakis[bis(trimethylsilyl)methyl]-,4-diisoheavier group 4 elements: germanium, tin, propyl--tetrasilyne, a stable compound with a silicon-silicon triple bond, which and lead ( ). However, despite bearing can be isolated as emerald green crystals stable up to 00 C in the absence of nominal triple bonds, these compounds acair. The Si!Si triple-bond length (and its estimated standard deviation) is tually exhibited a highly 4 pronounced non.06(9) angstroms, which shows half the magnitude of the bond shortening bonding electron density character at the of alkynes compared with that of alkenes. Unlike alkynes, the substituents at central atoms, resulting in a decrease in the the Si!Si group are not arranged in a linear fashion, but are trans-bent with bond order on descending group 4 (4, 9 a bond angle of 7.44(4). ). In light of these results, isolation of the silicon analog of alkynes has been a comwww.nature.com/scientificreports Hydrocarbons containing C"C double pelling goal. Although the theoretical analed the synthesis of the stable distannene bonds (alkenes) and C!C triple bonds ysis predicted the experimental accessibil[(me Si) CH] Sn"Sn[CH(SiMe ) ], where Me is methyl, which has a Sn"Sn 9ity of disilynes with a silicon-silicon triple (alkynes) form an abundant and structurally Siに結合した diverse class of organic compounds. HowAlの数を判別できる ever, the ability of heavier congeners of carbon (where element E is Si, Ge, Sn, and b) to form double bond of the type #E"E$ and triple bond of the type -E!Edocuments/o4_4.htm was for a long time doubted ( 4). The first attempts to generate such species were unδ 90 successful, resulting in the formation of Fig.. Schematic representations of molecular orbital diagrams of CBD. (A)SiSquare-shaped triplet. (B) polymeric substances. This led to the often- Rectangular-shaped Reaction. Science 004,(C) 0, 7. singlet from covalent second-order Jahn-Teller (J-T) distortion. Rhombic-shaped cited double-bond rule : Those elements singlet from polar second-order J-T distortion. Fig.. Molecular strucwww.nature.com/scientificreports with a principal quantum number equal to ture of,,4,4-tetor greater than three are not capable of rakis[bis(trimethylforming multiple bonds because of the consilyl)methyl]-, 4-disiderable auli repulsion between the elecisopropyl--tetrasilyne () (0% probability trons of the inner shells ( 7). Such a ellipsoids for Si and viewpoint prevailed despite the accumulac). Selected bond tion of a vast amount of experimental data lengths (Å): Si Si " supporting the existence of multiply bond.06(9), Si Si " ed species as reactive intermediates ( 4)..698(6), Si C " This conflict was resolved nearly 0 years.99(), Si C8 ".90(), and Si ago, when Lappert and Davidson report- Akira Sekiguchi,* Rei Kinjo, Masaaki Ichinohe Fig.. Theoretically puckered Dd structu tetrasilatetrahedrane, energy minima; a pl ture with two Si=Si rhombic Ch structu point structures (Fig. the valence isomers have been isolated isotropically bulky tb butyl) or dendriticall (where Me is methyl) (0, ). A square diene has also been r transition metal comp that bulky,,,, s-hydrindacen-4-yl might have the ability C ".980(6). Selected bond angles nar tetrasilacyclobutad Department of Chemistry, Graduate School of ure ( ): Si Si Si " observations of highly and Applied Sciences, University of Tsukuba, Tsukuba, 7.44(4), Si Si C frameworks comprisi Ibaraki 0 87, Japan. " 08.97(), Si Si C8 " 08.8(), Si Si C " 06.47(), C Si C8 " 06.8(6), C8 Si C " 4.77(7), and bonds (4, ). *To whom correspondence should be addressed. EWe now report th C Si C ".0(7). Estimated standard 0, deviations00, are in parentheses. mail: sekiguch@staff.chem.tsukuba.ac.jp δsi, 08 zation of the silicon (), stabilized by the Science 0,, SCIECE VOL 0 7 SETEMBER 004,,7,7-tetraethyl-,, 4-yl (EMind) group. has a planar rhomb pyramidal and plana silicon atoms. Clearly, groups on the silicon a 9 Sci. 0,, 64. rhombic four-membe Figure 9Si single pulse (S) andrep. Si-H cross polarization (C) magic angle sample spinning (MAS) spectra of non-aminosilanised diamagnetic silica nanoparticles. (a); condensed/polymerised ATS (b); silica nanoparticles aminosilanised in water (c) and silica nanoparticles aminosilanised via which is in contrast to TRE (d). Ch structure theoretic (SiH)4. silica-magnetite nanoparticles aminosilanised via TRE and water sequence was then subjected to CR and visualised by agarose gel The reduction o 使用例 ビーズ表面に形成した シロキサンの状態分析 8

9 MR MR, I = /, 00%, γ = %H O 4 = 0 =, = ~600 ppm (a) + xantphos ( eq), 80 C, min, in C 6 D 6, under H / (/, 0. Ma) h O h h h Ru δ h O h h h Ru 0 δ. H- (b) + xantphos ( eq), 0 C, min, in DMA, under H / (/, 0. Ma) (c) Rh(acac)() + xantphos ( eq) + (. eq), 0 C, min, in DMA, under H / (/, 0. Ma) H h h O Rh 7 δ 9. J Rh = Hz δ 7.7 free xantphos (d) Rh(acac)() + xantphos ( eq), 0 C, min, in DMA, under H / (/, 0. Ma) O two unidentified doublets δ 0.7, J = 48 Hz O δ 8., J = Hz Rh Ar = 4-nitrophenyl (e) Rh(acac)() + xantphos ( eq), 0 C, min, in DMA, under (0. Ma) (f) Rh(acac)() + xantphos ( eq), 80 C, min, in C 6 D 6, under H / (/, 0. Ma) (g) Rh(acac)() + xantphos ( eq), 0 C, min, in DMA, under Ar (0. Ma) O O O Rh Rh Rh O O O ' The MR spectra of admixtures of Rh(acac)(), xantphos, and. Angew. Chem. Int. Ed. 00, 49, M Fig. 4 MR traces for the time course of transesterification of p-nitrophenyl uridine H-phosphonate 4a with EtOH ( equiv.). ote the immediate consumption of L -4a in the first minute of the reaction. ew J. Chem. 00, 4, 84. 9