• Bulletin of the Korean Chemical Society
• /
• v.30 no.4
• /
• pp.849-852
• /
• 2009

The work describes EPR and 17O NMR measurements followed by theoretical calculation of the rotational correlation time $({\tau}_R)$, the water residence time $({\tau}_m)$, and the longitudinal electronic spin relaxation time $(T_{le})$(T_1e) for two new gadolinium complexes 1 and 2 of the type [$Gd(L)(H_2O)$] (L = tranexamic esters) in order to investigate their efficiency as a paramagnetic contrast agent (PCA). Of three correlation times, τR plays a major and predominant role to the unusually high relaxivity of 1 and 2 as compared with that of clinically approved MR CAs such as [$Gd(DTPA)(H_2O)]2‐ (Magnevist${\circledR}$), [Gd(DTPA-BMA)(H2O)] (Omniscan${\circledR}$), and $[Gd(DOTA)(H_2O)]^-$ (Dotarem${\circledR}$). The presence of bulky tranexamic ester in the ligand seems to be responsible for the conformational rigidity, which in turn causes such great an increase in ${\tau}_R$.

• Bulletin of the Korean Chemical Society
• /
• v.28 no.8
• /
• pp.1256-1260
• /
• 2007

Two β-diketone derivatives bearing triphenylene (1-naphthalene-2-yl-3-triphenylen-2-yl-propane-1,3-dione (NTPD)) and naphthalene (1,3-di-naphthalene-2-yl-propane-1,3-dione (DNPD)) and their Ln(III) complexes (Ln = Er or Gd) were synthesized and their photophysical properties were investigated. The sensitized emission of Er3+ ion in Er3+-[NTPD]3(terpy) and Er3+-[DNPD]3(terpy) was observed upon excitation at absorption maximum of ligands. Their photophysical studies indicate the sensitization of Er3+ luminescence by energy transfer through the excited triplet state of β-diketone ligand. The energy transfer rate through the excited triplet state of β-diketone ligand to Er3+ ion occurs faster than that of the oxygen quenching rate.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.10
• /
• pp.2900-2904
• /
• 2013

We present the synthesis and characterization of DTPA-bis(histidylamide) (1a), DTPA-bis(aspartamide) (1b), and their gadolinium complexes of the type $[Gd(L)(H_2O)]$ (2a:L = 1a; 2b:L = 1b). Thermodynamic stabilities and $R_1$ relaxivities of 2a-b compare well with Omniscan$^{(R)}$, a well-known commercial, extracellular (ECF) MRI CA which adopts the DTPA-bis(amide) framework for the chelate: $R_1$ = 5.5 and 5.1 $mM^{-1}$ for 2a and 2b, respectively. Addition of the Cu(II) ion to a solution containing 2b triggers relaxivity enhancement to raise $R_1$ as high as 15.3 $mM^{-1}$, which corresponds to a 300% enhancement. Such an increase levels off at the concentration beyond two equiv. of Cu(II), suggesting the formation of a trimetallic ($Gd/Cu_2$) complex in situ. Such a relaxivity increase is almost negligible with Zn(II) and other endogenous ions such as Na(I), K(I), Mg(II), and Ca(II). In vivo MR images and the signal-to-noise ratio (SNR) obtained with an aqueous mixture of 2b and Cu(II) ion in an 1:2 ratio demonstrate the potentiality of 2 as a copper responsive MRI CA.

• Bulletin of the Korean Chemical Society
• /
• v.18 no.11
• /
• pp.1158-1161
• /
• 1997

The potentiometric methods have been used to determined the protonation constants (logKiH) for the synthesized 1,7,13-trioxa-4,10,16-triazacyclooctadecane-N,N',N''-tri(methylacetic acid) [N3O3-tri(methylacetic acid)] and the stability constants (logKML) of the complexes of divalent and trivalent metal ions with the ligand N3O3-tri(methylacetic acid). The protonation constants of N3O3-tri(methylacetic acid) were 9.70 for logK1H, 9.18 for logK2H, 7.27 for logK3H, 3.38 for logK4H, and 2.94 for logK5H. The stability constants for the complexes of divalent metal ions with N3O3-tri(methylacetic acid) were 10.39 for Co2+, 10.68 for Ni2+, 13.45 for Cu2+, and 13.00 for Zn2+. The order of the stability constants for the complexes of the divalent metal ions with N3O3-tri(methylacetic acid) was Co2+ < Ni2+ < Zn2+ < Cu2+. The stability constants for the complexes of trivalent metal ions with N3O3-tri(methylacetic acid) were 16.20 for Ce3+, 16.40 for Eu3+, 16.27 for Gd3+, and 15.80 for Yb3+. The results obtained in this study were compared to those obtained for similar ligands, 1,7-dioxa-4,10,13-triazacyclopentadecane-N,N',N"-tri(methylacetic acid) and 1,7,13-trioxa-4,10,16-triazacyclooctadecane-N,N',N"-triacetic acid, which have been previously reported.

• Investigative Magnetic Resonance Imaging
• /
• v.10 no.1
• /
• pp.20-25
• /
• 2006

Purpose : To evaluate the NMR relaxation properties of newly developed high performance paramagnetic complexes. Materials and methods : 4-aminomethylcyclohexane carboxylic acid (0.63g, 4 mmol) was mixed with the suspension solution of DMF (15mL) and DTPA-bis-anhydride (0.71g, 2 mmol) to synthesize the ligand. The ligand was then mixed with Gd2O3 (0.18g, 0.5 mmol) to synthesize Gd-chelate. For the measurement of magnetic relaxivity of paramagnetic compounds, the compounds were diluted to 1mM and then the relaxation times were measured at 1.5T(64 MHz). Inversion-recovery pulse sequence was employed for T1 relaxation measurement and CPMG(Carr-Purcell-Meiboon-Gill) pulse sequence was employed for T2 relaxation measurement. Using MATLAB(Version 7.1) program, T1 magnetic relaxation map, R1 map, T2 magnetic relaxation map and R2 map were developed to represent magnetic relaxation time and magnetic relaxivity as image. Results : Compared to $R1=4.9mM^{-1}sec^{-1}$ and $R2=4.8mM^{-1}sec^{-1}$ of Omniscan (Gadodiamide), which is commercially available paramagnetic MR agent, R1 of SUK090(Gd-C32H74N5O24) was $12.46mM^{-1}sec^{-1}$ and R1 of SUK091(Gd-C34H78N5O24) was $12.77mM^{-1}sec^{-1}$. However, R1 of SUK092(Gd-C30H56N5O17) was decreased to $2.09mM^{-1}sec^{-1}$. In case of R2, SUK090(Gd-C32H74N5O24) was $8.76mM^{-1}sec^{-1}$ and SUK091(Gd-C34H78N5O24) was $7.60mM^{-}1sec^{-1}$ whereas SUK092(Gd-C30H56N5O17) was decreased to $1.82mM^{-1}sec^{-1}$. Conclusion : Among three new paramagnetic complexes, SUK090(Gd-C32H74N5O24) and SUK091(Gd-C34H78N5O24) showed higher T1, T2 magnetic relaxation rates than that of commercially available paramagnetic MR agent and thus expected to have more contrast enhancement effect.

• Bulletin of the Korean Chemical Society
• /
• v.28 no.8
• /
• pp.1249-1255
• /
• 2007

We have investigated the photophysical properties of dansyl-N-methylaminobenzoic acid (DABAH) as a ligand and its lanthanide (Ln3+)-cored complexes (Ln3+-(DABA)3(terpy)) in order to determine the main energy transfer pathway for sensitized near infrared emission of Ln3+ ions (Ln3+ = Nd3+ and Er3+) in Ln3+- (DABA)3(terpy). The fluorescence spectrum of DABAH shows a large Stokes shift with increasing solvent polarity. This large Stokes shift might be due to the formation of a twisted intramolecular charge transfer (TICT) state, as demonstrated by the large dipole moment in the excited state. It is in good agreement with the result that the phosphorescence even in the Gd3+-cored complex based on the DABAH ligand was not observed, maybe due to the highly forbidden character of the S1 → T1 transition in the DABAH ligand. A short decay component (ca. 1 ns) was observed in Er3+-(DABA)3(terpy) whereas the fluorescence lifetimes of DABAH and its Gd3+-(DABA)3(terpy) are observed about ~10 ns. The short component could be originated from the energy transfer process between the ligand and the Ln3+ ion. Based on the fluorescence of DABAH its Ln3+- (DABA)3(terpy), the sensitization of Ln3+ luminescence in the Ln3+-(DABA)3(terpy) takes place by the energy transfer via the TICT state of DABAH in the excited singlet state rather than via the excited triplet state.

• The Korean Journal of Nuclear Medicine
• /
• v.39 no.4
• /
• pp.215-223
• /
• 2005

Current interest in the regioselective N-functionalization of tetraazacycloalkanes (cyclen and cyclam) stems mainly from their complexes with radioactive metals for applications in diagnostic ($^{64}Cu,\;^{111}In,\;^{67}Ga$) and therapeutic ($^{90}Y$) medicine, and with paramagnetic ions for magnetic resonance imaging ($Gd^{+3}$). Selective methods for the N-substitution of cyclen and cyclam is a crucial step in most syntheses of cyclen and cyclam-based radiometal complexes and bifunctional chelating agents. In addition, mixing different pendent groups to give hetero-substituted cyclen derivatives would be advantageous in many applications for fine-tuning the compound's physical properties. So far, numerous approaches for the regioselective N-substitution of tetraazacycloalkanes and more specifically cyclen and cyclam are reported. Unfortunately, none of them are general and every strategy has its own strong points and drawbacks. Herein, we categorize numerous regioselective N-alkylation methods into three strategies, such as 1) direct substitution of the macrocycle, 2) introductiou of the functional groups prior to cyclization, and 3) protection/iunclionallrationideproteclion. Our discussion is also split into the methods of mono- and tri-functionalization and di-functionalizataion based on number of substituents. At the end, we describe new trials for the new macrocycles which iorm more stable metal complexes with various radiometals, and briefly mention the commercially available tetraazacycloalkanes which are used for the biconjugation of biomolecules.

• Investigative Magnetic Resonance Imaging
• /
• v.3 no.2
• /
• pp.159-166
• /
• 1999

Purpose : To evaluate the effect of rotational correlation time (${\tau}_R$) and the possible related changes of other parameters, ${\tau}_M,{\;}{\tau}_S,{\;}and{\;}(\tau}_V$ of gadolinium (Gd) chelate on T1 relaxation enhancement in two pool model. Materials and Methods : The NMRD (Nuclear Magnetic Relaxation Dispersion) profiles were simulated from 0.02 MHz to 800 MHz proton Larmor frequency for different values of rotational correlation times based on Solomon-Bloembergen equation for inner-sphere relaxation enhancement. To include both unbound pool (pool A) and bound pool (pool B), the relaxivity was divided by contribution from unbound pool and bound pool. The rotational correlation time for pool A was fixed at the value of 0.1 ns, which is a typical value for low molecular weight complexes such as Gd-DTPA in solution and ${\tau}_R$ for pool B was changed from 0.1 ns to 20 ns to allow the slower rotation by binding to macromolecule. The fractional factor of was also adjusted from 0 to 1.0 to simulate different binding ratios to macromolecule. Since the binding of Gd-chelate to macromolecule cab alter the electronic environment of Gd ion and also the degree of bulk water access to hydration site of Gd-chelate, the effects of these parameters were also included. Results : The result shows that low field profiles, ranged from 0.02 to 40 MHz, and dominated by contribution from bound pool, which is bound to macromolecule regardless of binding ratios. In addition, as more Gd-chelate bound to macromolecule, sharp increase of relaxivity at higher field occurs. The NMRD profiles for different values of ${\tau}_S$ show the enormous increase of low field profile whereas relaxivity at high field is not affected by ${\tau}_S$. On the other hand, the change in ${\tau}$V does not affect low field profile but strongly in fluences on both inflection fie이 and the maximum relaxivity value. The results shows a fluences on both inflection field and the maximum relaxivity value. The results shows a parabolic dependence of relaxivity on ${\tau}_M$. Conclusion : Binding of Gd-chelate to a macromolecule causes slower rotational tumbling of Gd-chelate and would result in relaxation enhancement, especially in clinical imaging field. However, binding to macromolecule can change water enchange rate (${\tau}_M$) and electronic relaxation ($T_le$) vis structural deformation of electron environment and the access of bulk water to hydration site of metal-chelate. The clinical utilities of Gd-chelate bound to macromolecule are the less dose requirement, the tissue specificity, and the better perfusion and intravascular agents.

• Bulletin of the Korean Chemical Society
• /
• v.31 no.5
• /
• pp.1283-1288
• /
• 2010

A novel polyaminopolycarboxylate ligand with many coordination sites, N,N,$N^1,N^1,N^2,N^2$-[( 2,4,6-tri(aminomethyl)-pyridine]hexakis(acetic acid) (TPHA), was designed and synthesized and its lanthanide complexes $Na_6Tb_2$(TPHA)$Cl_6{\cdot}14H_2O$, $Na_6Eu_2$(TPHA)$Cl_6{\cdot}8H_2O$, $Na_6Gd_2$(TPHA)$Cl_6{\cdot}11H_2O$ and $Na_6Sm_2$(TPHA)$Cl_6{\cdot}9H_2O$ were successfully prepared. The ligand and the complexes were characterized by elemental analysis, IR, mass, NMR and TG-DTA. The TG-DTA studies indicated that the complexes had a high thermal stability, whose initial decomposition temperature was over $270^{\circ}C$. The luminescence properties of the complexes in solid state were investigated and the results suggested that $Tb^{3+}$ and $Eu^{3+}$ ions could be sensitized efficiently by the ligand, especially the Tb(III) complex displayed a very strong luminescence intensity (> 10000) and only displayed characteristic metal-centered luminescence. Also, the correlative comparison between the structure of ligand and luminescence properties showed how the number of the coordination atoms of ligand can be a prominent factor in the effectiveness of ligand-to-metal energy transfer.

• The Journal of Natural Sciences
• /
• v.7
• /
• pp.37-46
• /
• 1995

Electrochemical behavior of $Ln^{3+},$-ALC complexes($Gd^{3+},$ $Tb^{3+},$ $Dy^{3+},$ $Ho^{3+},$ $Er^{3+},$ $Yb^{3+}$ and $Lu^{3+}$-alizarin complex-one) has been investgated by d.c polarography, differential pulse polarography and cyclic voltammetry. The reduction mechanism of ALC comes to the conclusion that the two electron make one step of reversible processes, and that there is few adsorption in the electrode reaction. The new complex is made from one lanthanide ion and one ALC. This complex is proven to make an adsorptive complex wave, by the experiments of differential pulse polarography and cyclic voltammetry. The reduction potential of complex wave($P_2$)turns up more negatively than ligand wave($P_1$) does. Linear calibration curves of the decreasing P1 and increasing $P_2$ is obtained when the lanthanide concentration varys from $2.5X10^5$M to $1X10^4M$.