¹¹B NMR Sensing of d-Block Metal Ions in Vitro and in Cells Based on the Carbon–Boron Bond Cleavage of Phenylboronic Acid-Pendant Cyclen (Cyclen = 1,4,7,10-Tetraazacyclododecane)

Abstract

Noninvasive magnetic resonance imaging (MRI) including the "chemical shift imaging (CSI)" technique based on (1)H NMR signals is a powerful method for the in vivo imaging of intracellular molecules and for monitoring various biological events. However, it has the drawback of low resolution because of background signals from intrinsic water protons. On the other hand, it is assumed that the (11)B NMR signals which can be applied to a CSI technique have certain advantages, since boron is an ultratrace element in animal cells and tissues. In this manuscript, we report on the sensing of biologically indispensable d-block metal cations such as zinc, copper, iron, cobalt, manganese, and nickel based on (11)B NMR signals of simple phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane), L(6) and L(7), in aqueous solution at physiological pH. The results indicate that the carbon-boron bond of L(6) is cleaved upon the addition of Zn(2+) and the broad (11)B NMR signal of L(6) at 31 ppm is shifted upfield to 19 ppm, which corresponds to the signal of B(OH)(3). (1)H NMR, X-ray single crystal structure analysis, and UV absorption spectra also provide support for the carbon-boron bond cleavage of ZnL(6). Because the cellular uptake of L(6) was very small, a more cell-membrane permeable ligand containing the boronic acid ester L(7) was synthesized and investigated for the sensing of d-block metal ions using (11)B NMR. Data on (11)B NMR sensing of Zn(2+) in Jurkat T cells using L(7) is also presented.

11B NMR/MRI Sensing of Copper(II) Ions In Vitro by the Decomposition of a Hybrid Compound of anido‐o‐Carborane and a Metal Chelator

“…The intracellular uptake of 3 , 4 , 7 , and 9 was determined by ICP‐AES (249.733 nm) or ICP‐MS, and the results are shown in Figure . Cellular uptake of other closo ‐ o ‐carborane derivatives 3 , 7 , and 9 was observed to some extents, while the uptake of 4 by Jurkat T cells was quite low (0.022 fmol as molecule [0.20 fmol as boron atom per cell]).…”

Dynamic cyclen–metal complexes for molecular sensing and chirality signaling

“…Sharp 11 B NMR signals of B(OH) 3 of 9 appeared in the in-cell NMR spectrum in response to the Zn(II) concentration in Jurkat T cells. 23 When an armed cyclen forms a transition metal complex, all the coordination sites of the metal center are not occupied by the donors of the armed cyclen. Since the remaining coordination site can accommodate a solvent molecule or a co-existing anion, this site can be occupied externally by more coordinative species in solution.…”

Asymmetric Aldol Reactions between Acetone and Benzaldehydes Catalyzed by Chiral Zn2+ Complexes of Aminoacyl 1,4,7,10‐Tetraazacyclododecane: Fine‐Tuning of the Amino‐Acid Side Chains and a Revised Reaction Mechanism

“…The ligands for ZnL complexes [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] were synthesized from 3Boc-cyclen (Boc = tert-butoxycarbonyl) [12] with N-Boc-protected amino-acid derivatives, as described in our previous paper. [10,11] The ZnL complexes were prepared in situ immediately before use by reacting the acidfree ligand with Zn 2+ ions.…”

“…[16][17][18] For instance, the Zn 2+ -bound HO À group in the class-II aldolase model complex 35 b (ZnL 20 A C H T U N G T R E N N U N G (OH À )) is considered to deprotonate the a proton to the carbonyl group of the phenacyl side chain to give Zn 2+ À enolate 35 c (ZnA C H T U N G T R E N N U N G (H -1 L 20 )) in aqueous solution (Scheme 4). [16][17][18] For instance, the Zn 2+ -bound HO À group in the class-II aldolase model complex 35 b (ZnL 20 A C H T U N G T R E N N U N G (OH À )) is considered to deprotonate the a proton to the carbonyl group of the phenacyl side chain to give Zn 2+ À enolate 35 c (ZnA C H T U N G T R E N N U N G (H -1 L 20 )) in aqueous solution (Scheme 4).…”

“…These results were applied to the one-pot synthesis of optically active 1,3-diols (9 a-9 c) through a combination of enantioselective aldol reactions catalyzed by l-and d-phenylalanylpendant cyclens 3 and 4 (l-ZnL 3 and d-ZnL 3 ), thus affording 1,2-adducts 8 a-8 c with their successive reduction by the recombinant oxidoreductase system Chiralscreeen OH. We synthesized various ZnL complexes that contained aliphatic, aromatic, anionic, cationic, and dipeptide side chains (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). We synthesized various ZnL complexes that contained aliphatic, aromatic, anionic, cationic, and dipeptide side chains (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”