【正文】 ters can provide a wealth of diagnostic addition, the desired crosssection for acquiring multiangle and multiplanar images of various parts of the entire body can be freely chosen by adjusting the MRI magnetic eld。most of them have focused on the development of targeted, high relaxivity and bioactivated contrast responsive gadolinium(III)based MRI contrast agents can be modulated by particular in vivo stimuli including pH,28–35 metal ion concentration36–43 and enzyme –50 Notably, a number of copperresponsive MRI contrast agents have been reported to detect uctuations of copper ions in –58 These activated contrast agents exploit the modulation of the number of coordinated water molecules to generate distinct enhancements in longitudinal relaxivity in response to copper ions(Cu+ or Cu2+).In this study, we designed and synthesized a binuclear gadoliniumbased MRI contrast agent, [Gd2(DO3A)2BMPNA], that is specically responsive to Cu2+ over other biologicallyrelevant metal new copperresponsive MRI contrast agent prises two GdDO3A cores connected by a 2,6bis(3methyl1Hpyrazol1yl)isonicotinic acid scaffold59,60(BMPNA), which functions as a receptor for copperinduced relaxivity synthetic strategy for [Gd2(DO3A)2BMPNA] is depicted in Scheme , the T1 relaxivity of [Gd2(DO3A)2BMPNA] was studied at 25 C and 60 MHz in the absence or presence of Cu2+.Experiments to determine the selectivity of [Gd2(DO3A)2BMPNA] towards Cu2+ over other biologicallyrelevant ions were carried out as lifetime was measured to determine the number of coordinated water molecules(q)of [Gd2(DO3A)2BMPNA] in the absence or presence of Cu2+.In addition, T1weighted phantom images were collected to visualize the relaxivity enhancement caused by Cu2+, suggesting potential in vivo sectionMaterials and instrumentsAll materials for synthesis were purchased from mercial suppliers and used without further and 13C NMR spectra were taken on an AMX600 Bruker FTNMR spectrometer with tetramethylsilane(TMS)as an internal measurements were performed on a Hitachi Fluorescence timeresolved luminescence emission spectra were recorded on a PerkinElmer LS55 uorimeter with the following conditions: excitation wavelength, 295 nm。cycle time, 20 ms。 50 ns)as the excitation(Continuum Sunlite OPO).Mass spectra(MS)were obtained on an auto ex III TOF/TOF MALDIMS and anIonSpec ESIFTICR mass analyses were performed on a Vario EL Element Synthesis of pound 2,6bis(3(bromomethyl)1Hpyrazol1yl)isonicotinate(Compound1)59,60 and 4,7,10tris(2(tertbutoxy)2oxoethyl)4,7,10triazaazoniacyclododecan1ium bromide(Compound 2)61 were prepared following thereported 2( g, mmol)was suspended in 2 ml anhydrous acetonitrile with 6 equivalents of NaHCO3( g)and the mixture was stirred at room temperature for 1( g, mmol)was added, and the mixture was slowly heated to reflux(80 C)and stirred the reaction was terminated, the mixture was cooled to room temperature, and the solution was precipitate was washed several times with anhydrous acetonitrile, and the collected ltrate solution was evaporated under reduced residue was puried using silicagel column chromatography eluted with CH2Cl2–nhexane–CH3OH(10 : 3 : 1, v/v/v)to afford Compound 3( g, 53%)as a pale yellow NMR(600 MHz, DMSO): (s, 2H), (s, 2H), (s, 2H), (s, 4H), (s, 3H), (m, 4H), (m, 8H), (s, 8H), (m, 24H), (s, 54H)(?).13C NMR(151 MHz, CDCl3): d , , , , , , , , , , , , , , , , , , (?).HRMS(ESI): m/z C67H111N13O14 [M + 2H]2+ , [M + H + Na]2+ , [M + 2Na]2+ , found [M + 2H]2+ , [M+ H + Na]2+ , [M + 2Na]2+ (?).Synthesis of pound 3( g, mmol)was stirred with triuoroacetic acid in methylene chloride solution(2 ml)at room temperature for 24 solvent was then evaporated under reduced pressure, and the residue was washed three times in CH3OH and CH2Cl2 to eliminate excess obtained residue was dissolved with a minimum volume of CH3OH and precipitated with cold precipitate was ltered to afford a brown yellow solid( g).1H NMR(600 MHz, DMSO): (s, 2H), (s, 2H), (s, 2H), (s, 4H), (s, 3H), (b, 20H), (m, 24H)(?).13C NMR(151 MHz, D2O): d , , , , , , , , , , , , , , , , (?).MALDITOFMS spectrum(CH3OH): m/z C43H63N13O14 [M H] , found (?).Anal C43H63N13O14$3CF3COOH$2H2O: C, 。H, 。 50 ns)as the excitation(Continuum Sunlite OPO).Samples were excited at 290 nm, and the emission maximum(545 nm)was used to determine luminescence Tb(III)based emission spectra were measured using mM solutions of Tb plex analog in 100 mM HEPES buffer at pH in H2O and D2O in the absence and presence of Cu2+.The number of coordinated water molecules(q)was calculated according to eqn(2):62,63 q= 188。TE= 13 ms。however, studies with analogous Gd3+DO3A plexes demonstrated that this ligand is more kinetically inert to metalion To ensure the kinetic stability of the plex, we used MS to monitor [Gd2(DO3A)2BMPNA] in the presence of 1 Zn2+.No metalion exchange was observed at room temperature after 7 days(?).Relaxivity interference experiments for [Gd2(DO3A)2BMPNA] in the presence of both Cu2+( mM)and other biologicallyrelevant metal ions were also conducted。the image intensity was a bit darker than that of our contrast In conclusion, we designed and synthesized a novel bismacrocyclic DO3Atype Cu2+responsive MRI contrast agent, [Gd2(DO3A)2BMPNA].The new Cu2+responsive MRI contrast agent prised two GdDO3A cores connected by a 2,6bis(3methyl1Hpyrazol1yl)isonicotinic acid scaffold(BMPNA)that functioned as a Cu2+ receptor switch to induce a distinct relaxivity enhancement in response to Cu2+。 Sons, Ltd., New York, , , and , ., 2010, 110, , and , ., 1998, 27, , and , ., 2006, 35, , ., 1987, 87, , and , ., 2005, 57, , ., 1955, 99, , ., 1957, 27, and , ., 1961, 34, and , ., 2010, 39, and 180。oth, , , 180。opez, , 180。在這個(gè)世界里，喝一口水就能縮得如同老鼠大小，吃一塊蛋糕又會(huì)變成巨人，在這個(gè)世界里，似乎所有吃的東西都有古怪?！稅埯惤z穿鏡奇幻記》講述的是小姑娘愛麗絲剛下完一盤國際象棋，又對(duì)鏡子里反映的東西好奇不已，以致穿鏡而入，進(jìn)入了鏡子中的象棋世界。看來只有發(fā)明家兼廢品收藏家白騎士無法歸類，但他恰好是作者本人的化身。道奇遜，與安徒生、格林兄弟齊名的世界頂尖兒童文學(xué)大師。1832年