Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrier: an 17 O and 1 H relaxation study of its Gd(III) coplex Petra Lebdušková, ab Angélique Sour, b Lothar Hel,* b Éva Tóth, bc Jan Kotek, a Ivan Lukeš * a and André E. Merbach b a Departent of Inorganic Cheistry, Charles University, Hlavova 030, 1840 Prague, Czech Republic. Fax: +40 195 153; Tel: +40 195 159; E-ail: lukes@natur.cuni.cz b Institut des Sciences et Ingénierie Chiiques, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Fax: +41 1 693 98 75; Tel: +41 1 693 98 76; E-ail: lothar.hel@epfl.ch c Centre de biophysique oléculaire, CNRS, rue Charles-Sadron, 45071 Orléans, Cedex, France. Suppleentary inforation Appendix. Equations used in the analysis of 17 O NMR and 1 H NMRD data. Table S1. Proton relaxivities (r 1 / M -1 s -1 ) of G5-(Gd(DTTAP)) 63, c(gd III )=5.3 M, ph=6.5, at variable teperature. Table S. Proton relaxivities (r 1 / M -1 s -1 ) of [Gd(DTTAP-bz-NH )(H O)] -, c(gd III )=4. M, ph=6.75, at variable teperature. Table S3. Proton relaxivities (r 1 / M -1 s -1 ) of [Gd(DTTAP-bz-NO )(H O)] -, c(gd III )=3.8 M, ph=6.59, at variable teperature. Table S4. Variable teperature reduced transverse and longitudinal 17 O relaxation rates of G5- (Gd(DTTAP)) 63, c(gd III )=39 M, ph=5.69, P =7.95 10-4 at 9.4 T. Reference was G5-(Y(DTTAP)) 63, c(y III )=34 M, ph=5.83. Table S5. Variable teperature reduced transverse and longitudinal 17 O relaxation rates of G5- (Gd(DTTAP)) 63, c(gd III )=39 M, ph=5.69, P =7.95 10-4 at 4.7 T. Reference was G5-(Y(DTTAP)) 63, c(y III )=34 M, ph=5.83. Table S6. Variable teperature reduced transverse and longitudinal 17 O relaxation rates of [Gd(DTTAP-bz-NH )(H O)] -, c(gd III )=46 M, ph=5.51, P =8.19 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. Table S7. Variable teperature reduced transverse and longitudinal 17 O relaxation rates of [Gd(DTTAP-bz-NO )(H O)] -, c(gd III )=3 M, ph=5.91, P =5.73 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. Table S8. Calculation of the nuber of chelating groups per dendrier. Figure S1. Variable teperature reduced 17 O cheical shifts of [Gd(DTTAP-bz-NO )(H O)] -, c(gd III )=3 M, ph=5.91, P =5.73 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. Figure S. Variable teperature reduced 17 O cheical shifts of [Gd(DTTAP-bz-NH )(H O)] -, c(gd III )=46 M, ph=5.51, P =8.19 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. Figure S3. Variable teperature reduced 17 O cheical shifts of G5-(Gd(DTTAP)) 63, c(gd III )=39 M, ph=5.69, P =7.95 10-4 at 4.7 T and 9.4 T. Reference was G5-(Y(DTTAP)) 63, c(y III )=34 M, ph=5.83. Table S9. Fitted paraeters of G5-(Gd(DTTAP)) 63. Table S10. Fitted paraeters of [Gd(DTTAP-bz-NO )(H O)] - and [Gd(DTTAP-bz-NH )(H O)] -. The underlined paraeters were fixed during the fitting. 1
Equations. 17 O NMR relaxation: Fro the easured 17 O NMR relaxation rates and angular frequencies of the paraagnetic solutions, 1/T 1, 1/T and ω, and of the acidified water reference, 1/T 1A, 1/T A and ω A, one can calculate the reduced relaxation rates, 1/T 1r, 1/T r (Eq. [1] and []), where 1/T 1, 1/T are the relaxation rates of the bound water and Δω is the cheical shift difference between bound and bulk water, τ is the ean residence tie or the inverse of the water exchange rate k ex and P is the ole fraction of the bound water. 1, 1 1 1 1 1 1 = T1r P T1 T = + [1] 1A T1 + τ T1 OS 1 1 1 1 1 T + τ T +Δω 1 T P T T + +Δ T S 1 1 = = + 1 1 r A τ τ ω O ( T ) The ters 1/T 1OS and 1/T OS describe relaxation contributions fro water olecules not directly bound to the paraagnetic centre. In previous studies it has been shown that 17 O outer sphere relaxation ters due to water olecules freely diffusing on the surface of Gd-polyainocarboxylate coplexes are negligible. For coplexes with phosphate groups relaxation ters due to nd sphere water olecules can however be iportant for longitudinal relaxation 1/T 1r and have therefore to be included. 1 1 = + = + [3] 1st nd nd T1r T1r T1r T1 + τ T1r 1 1 T + τ T +Δω = = [4] 1st 1 1 Tr T r τ τ + T +Δω ( ) First sphere contribution to 17 O relaxation: The 17 O longitudinal relaxation rates in Gd(III) solutions are the su of the contributions of the dipole-dipole and quadrupolar (in the approxiation developed by Halle for non-extree narrowing conditions) echaniss as expressed by Eq. [6]-[7], where γ S is the electron and γ I is the nuclear gyroagnetic ratio (γ S = 1.76 1011 rad s -1 T -1, γ I =-3.66 10 7 rad s -1 T -1 ), r GdO is the effective distance between the electron charge and the 17 O nucleus, I is the nuclear spin (5/ for 17 O), χ is the quadrupolar coupling constant and η is an asyetry paraeter: = + [5] T T T 1 1dd 1q 0 I S 6 rgdo 1 = S( S 1) 3 J ( I; d1) 7 J ( S; d) ; J ( ; ) T1 dd 15 μ γ γ ω τ ω τ ω τ τ 4π + + = [6] 1 + ( ωτ ) 1 τ = d1 τ + T + 1e τr O 1 3π I + 3 η τ = χ 1 + 0. J1( ωi; τro) + 0.8 J ( ωi; τro) ; Jn ( ω; τ) = [7] T1 q 10 I ( I 1) 3 1 + ( nωτ ) In the transverse relaxation the scalar contribution, 1/T sc, is doinating, Eq. [8]. 1/τ s1 is the su of the exchange rate constant and the electron spin relaxation rate. 1 1 S( S + 1) A = τ [8] S1 T TSC 3 = + [9] τ τ S1 T1 e []
For slowly rotating species with internal degrees of freedo, the spectral density functions J are described the Lipari-Szabo approach. 3,4 In this odel we distinguish two statistically independent otions; a rapid local otion with a correlation tie τ l and a slower global otion with a correlation tie τ g. Supposing the global olecular reorientation is isotropic, the relevant spectral density functions are expressed as in Eq. [10]-[13], where the general order paraeter S describes the degree of spatial restriction of the local otion. If the local otion is isotropic, S =0; if the rotational dynaics is only governed by the global otion, S =1. S τ ( 1 S ) τ dig di J ( ωτ ; di ) = + 1+ ωτdig 1+ ωτ di [10] 1 τ τ τ 1 O T τ τ τ T ; i = 1, [11] dig g ie = + O O τ τ τ J n ( ω) g l S τ g = + 1 + ( nωτ g ) 1 + di ie O ( 1 S ) τ O ( nωτ ) [1] [13] Second sphere contribution to 17 O relaxation: nd nd 1 q 1 q 1 1 = nd 1st nd 1st + nd nd T1 q T1 q T1dd T 1q 1 3τ =C + nd,o nd,o nd,o d1 d nd dd T1dd 1+ ωτ 1+ ωτ 7τ nd,o nd,o ( I d1 ) ( S d ) nd,o μ 17 0 h γ γ O S C dd = S S+1 nd 6 15 4π r ( GdO ) ( ) 1 3π I + 3 0.τ 0.8τ ( ) T I I 1 1+ ωτ 1+ ωτ nd,o nd,o = χ 1+η 3 + nd 1q 10 ( ) = + 1 τ τ τ τ O,nd O O g l l τ τ nd =k nd,o ex + + O,nd di T ie [14] nd,o nd,o ( I ) ( I ) [15] [16] [17] [18] 1 H NMRD: obs The easured longitudinal proton relaxation rate, R 1 is the su of a paraagnetic and a diaagnetic contribution as expressed in Eq. [19], where r 1 is the proton relaxivity: obs d p d 3 R = R + R = R + r Gd + [19] 1 1 The relaxivity is here given by the su of inner sphere, second sphere and outer sphere contributions: r = r + r + r [0] 1 1is 1,nd 1os Inner sphere 1 H relaxation: The inner sphere ter is given in Eq. [1], where q 1st is the nuber of inner sphere water olecules. 5 3
1st 1 q 1 r1 is = [1] H 1000 55.55 T1 + τ The longitudinal relaxation rate of inner sphere protons, 1/T H 1 is expressed by Eq. [], where r GdH is the effective distance between the electron charge and the 1 H nucleus, ω I is the proton resonance frequency and ω S is the Laror frequency of the Gd(III) electron spin. 1 μ0 γ Iγ S = S 6 ( S 1) 3 J( I; d1) 7 J( S; H + ω τ + ω τd ) T 15 4π r [] 1 GdH ( 1 S ) S τ τ dig di J ( ωτ ; di ) = + ; i = 1, [3] 1+ ωτdig 1+ ωτ di 1 τ = τ + τ + T ; 1 H τ = τ + τ + T ; i = 1, [4] dig g ie = + H H τ τg τl dig ie The spectral density functions are given by Eq. [3]. Second sphere 1 H relaxation: [5] nd nd nd 1 q 1 1 q 1 1 T nd,h nd,h 1dd + τ nd T 1dd r = 1000 55.55 1000 55.55 1 3τ nd,h nd,h nd,o d1 d =C nd,h dd + T1dd 1+ ωτ 1+ ωτ 7τ nd,h nd,h ( I d1 ) ( S d ) nd,h μ 1 0 h γ γ H S C dd = S S+1 nd 6 15 4π r ( GdO ) =k + + nd nd,h ex H τdi τ Tie = + H H τ τg τl ( ) [6] [7] [8] [9] [30] Outer sphere 1 H relaxation: The outer-sphere contribution can be described by Eq. [31] where N A is the Avogadro constant, and J os is its associated spectral density function. 6,7 3N Aπ μ0 γ Sγ I 1os = + os I 1e + os S e 405 4π agdh DGdH ( 1) 3 ( ω ; ) 7 ( ω ; ) r S S J T J T [31] 1/ 1 τ GdH 1+ iωτgdh + 4 Tje Jos ( ω, Tje ) = Re ; j = 1, [3] 1/ 3/ τ GdH 4 τ GdH 1 τ GdH 1+ iωτgdh + + iωτgdh + + iωτ GdH + T je 9 T je 9 T je agdh τ GdH = [33] DGdH a GdH is the distance of closes approach and D GdH is the diffusion coefficient for the diffusion of a water proton relative to the Gd(III) coplex. 4
Electron spin relaxation: The longitudinal and transverse electronic relaxation rates, 1/T 1e and 1/T e are described by Soloon- Bloebergen-Morgan theory odified by Powell (Eqs. [34]-[35]), where τ V is the correlation tie for the odulation of the zero-field-splitting interaction. ZFS 1 1 1 4 { 4S( S 1) 3} = Δ τ v + + T1 e 5 1 + ωsτv 1 + 4ωSτv ZFS 1 5.6 7.18 =Δ τ v + T e 1 + 0.37ωSτv 1 + 1.4ω S τ v [34] [35] Teperature dependences of water exchange rates and correlation ties: The exchange rates are supposed to follow the Eyring equation. In Eq. [36] ΔS and ΔH are the entropy and enthalpy of activation for the water exchange process, and k 98 ex is the exchange rate at 98.15 K. In Eq. [37] ΔH nd is the enthalpy of activation for the second sphere water exchange process and k nd,98 ex is the corresponding exchange rate at 98 K. 98 1 kt B ΔS ΔH kex T ΔH 1 1 kex = = exp = exp [36] τ h R RT 98.15 R 98.15 T nd,98 nd nd kex ΔH 1 1 [37] kex = exp 98.14 T 98.15 T All correlation ties and the diffusion constant are supposed to obey an Arrhenius law: 98 E 1 1 exp a τ = τ R T 98.15 [38] 98 EGdH 1 1 DGdH = DGdH exp R 98.15 T [39] 5
Table S1: Proton relaxivities (r 1 / M -1 s -1 ) of G5-(Gd(DTTAP)) 63, c(gd III )=5.3 M, ph=6.5, at variable teperature. ν ( 1 H)/MHz 5 C 15 C 5 C 37 C 50 C 0.010.6 3..5 0. 18.1 0.014.7 3.4.3 0.3 18.1 0.01.4 3.4.5 0.1 18.0 0.030.4 3.4.4 0. 18.1 0.043. 5 3.4.4 0.3 18.1 0.06.5 3.3.5 0.3 18.0 0.089.5 3.3.5 0.1 18.0 0.17.5 3.3.3 0.1 17.9 0.183.4 3..3 0.1 17.9 0.64.3 3.. 0.1 17.8 0.379.0.8 1.9 19.8 17.5 0.546 1.8.4 1.6 19.4 17. 0.784 1.1 1.8 1.0 18.8 16.7 1.13 0.6 1.3 0.4 18. 16. 1.6 19.9 0.5 19.6 17.7 15.6.34 19.1 19.9 18.8 16.7 15.0 3.36 18.5 19.0 18.0 16. 14.4 4.83 17.9 18.8 17.3 15.6 13.7 6.95 17.5 19.0 17. 15.5 13.4 10.0 1.4. 1.5 18.8 16.4 11.5.8-3.0 0.0 17.7 1.0-3.9 - - - 13. 3.8-4.7 1.6 18.9 13.6-4.9 - - - 15. 5.1-6.5 3.5 0.3 15.5-6.4 - - - 17.4 6.0-8.3 5.. 17.6-7.6 - - - 0 7.6 8.8 30.4 6.8 3.5 30 6.0 9.4 30.6 8.5 4.1 40 4.7 7.9 8.9 7.3 3.5 60 0.6.4 3.0. 0 19.8 100 14.8 14.8 14.7 14.1 13. 00 9.10 8.74 8.34 7.83 7.55 6
Table S: Proton relaxivities (r 1 / M -1 s -1 ) of [Gd(DTTAP-bz-NH )(H O)] -, c(gd III )=4. M, ph=6.75, at variable teperature. ν ( 1 H)/MHz 5 C 5 C 37 C 50 C 0.010 14.0 9.58 8.0 6.6 0.014 14.0 9.56 8.07 6.6 0.01 14.0 9.63 7.99 6.30 0.030 13.8 9.61 7.93 6.6 0.043 13.9 9.64 8.15 6.5 0.06 13.9 9.61 8.06 6. 0.089 14.0 9.56 8.04 6. 0.17 14.0 9.59 8.05 6.5 0.183 13.9 9.59 8.04 6. 0.64 14.0 9.58 8.07 6.5 0.379 13.9 9.53 8.11 6.5 0.546 13.5 9.56 7.98 6.18 0.784 13.7 9.48 7.99 6.17 1.13 13.5 9.37 7.85 6.15 1.6 13. 9.7 7.86 6.07.34 1.7 9.11 7.68 6.00 3.36 1.3 8.76 7.49 5.87 4.83 11.6 8.7 7.0 5.64 6.95 10.9 7.81 6.7 5.36 10.0 11.1 7.7 5.97 4.80 10.0 11.0 - - - 11.6 10.9 7.08 5.68 4.55 13.4 10.8 6.87 5.39 4.34 15.5 10.8 6.6 5.0 4.09 18 10.8 6.44 4.97 3.93 0 10.7 6.34 5.0 4.08 30 10.6 6.34 4.75 3.76 40 10.6 6. 4.60 3.61 60 10.6 6.3 4.51 3.46 100 10.3 6.08 4.43 3.4 00 9.48 5.88 4.6 3.3 400 7.9 5.49 4.19 3.4 7
Table S3: Proton relaxivities (r 1 / M -1 s -1 ) of [Gd(DTTAP-bz-NO )(H O)] -, c(gd III )=3.8 M, ph=6.59, at variable teperature. ν ( 1 H)/MHz 5 C 5 C 37 C 50 C 0.010 14. 10.1 8. 6.8 0.014 14. 10.1 8.4 6.84 0.01 14.3 10.1 8.4 6.81 0.030 14.3 10.1 8.1 6.84 0.043 14. 10.1 8. 6.80 0.06 14. 10.1 8.4 6.81 0.089 14. 10.1 8. 6.80 0.17 14. 10.1 8.1 6.81 0.183 14. 10.1 8.19 6.79 0.64 14.1 10.1 8.18 6.79 0.379 14.1 10.1 8.0 6.78 0.546 14.0 10.1 8.15 6.74 0.784 13.8 9.99 8.13 6.75 1.13 13.6 9.81 8.04 6.68 1.63 13.3 9.67 7.96 6.59.34 1.8 9.43 7.7 6.48 3.36 1.4 9.07 7.48 6.6 4.83 11.6 8.58 7.08 5.94 6.95 11.0 7.77 6.54 5.49 10.0 10.9 7.58 6.07 5.16 11.5 10.7 7.7 5.84 4.93 13. 10.8 7.04 5.61 4.68 15. 10.6 6.87 5.34 4.45 17.4 10.6 6.7 5.16 4.31 0 10.7 6.76 5.4 4.34 30 10. 6.34 4.74 3.76 40 10. 6.7 4.60 3.61 60 10.3 6.3 4.51 3.47 100 9.90 6.01 4.45 3.39 00 9.36 5.84 4.3 3.3 400 8.3 5.46 4.3 3.3 8
Table S4: Variable teperature reduced transverse and longitudinal 17 O relaxation rates of G5-(Gd(DTTAP)) 63, c(gd III )=39 M, ph=5.69, P =7.95 10-4 at 9.4 T. Reference was G5-(Y(DTTAP)) 63, c(y III )=34 M, ph=5.83. t / C T / K 1000/T / K -1 T 1 (Gd)/s T 1 (Y)/s T (Gd)/s T (Y)/s ln(1/t 1r ) ln(1/t r ) 5.4 78.6 3.59.41E-03.80E-03 9.15E-04.00E-03 11.19 13.5 10.7 83.9 3.5.91E-03 3.39E-03 8.38E-04.47E-03 11.0 13.81 18.3 91.5 3.43 3.47E-03 4.31E-03 6.80E-04 3.4E-03 11.16 14.0 3.6 96.8 3.37 3.93E-03 5.0E-03 6.87E-04 3.9E-03 11.15 14.3 30.3 303.5 3.30 4.59E-03 6.11E-03 7.0E-04 5.00E-03 11.13 14.5 40. 313.4 3.19 5.60E-03 7.83E-03 9.5E-04 6.77E-03 11.07 13.98 49. 3.4 3.10 6.73E-03 9.6E-03 1.16E-03 8.6E-03 10.93 13.75 59.7 33.9 3.00 7.99E-03 1.19E-0 1.66E-03 1.10E-0 10.86 13.38 70.5 343.7.91 9.6E-03 1.47E-0.49E-03 1.40E-0 10.7 1.94 81.3 354.5.8 1.17E-0 1.78E-0 3.76E-03 1.71E-0 10.51 1.47 Table S5: Variable teperature reduced transverse and longitudinal 17 O relaxation rates of G5-(Gd(DTTAP)) 63, c(gd III )=39 M, ph=5.69, P =7.95 10-4 4.7 T. Reference was G5-(Y(DTTAP)) 63, c(y III )=34 M, ph=5.83. t / C T / K 1000/T / K -1 T 1 (Gd)/s T 1 (Y)/s T (Gd)/s T (Y)/s ln(1/t 1r ) ln(1/t r ) 6.0 79. 3.58.05E-03.68E-03 8.98E-04 1.93E-03 11.89 13.53 10.3 83.5 3.53.31E-03 3.14E-03 9.1E-04.30E-03 11.88 13.63 14.3 87.5 3.48.48E-03 3.5E-03 7.81E-04.67E-03 11.9 13.95 18.8 9.0 3.43.74E-03 4.11E-03 8.41E-04 3.13E-03 11.94 13.91 4.1 97.3 3.36 3.15E-03 4.88E-03 8.5E-04 3.83E-03 11.86 13.95 9.6 30.8 3.30 3.57E-03 5.64E-03 8.47E-04 4.58E-03 11.77 14.01 37. 310.4 3. 4.3E-03 6.94E-03 1.06E-03 5.90E-03 11.66 13.78 47.9 31.1 3.11 5.7E-03 8.86E-03 1.7E-03 7.90E-03 11.48 13.63 58.7 331.9 3.01 6.5E-03 1.14E-0 1.81E-03 1.05E-0 11.3 13.6 71.1 344.3.90 8.58E-03 1.45E-0.7E-03 1.35E-0 10.99 1.8 81.8 355.0.8 1.09E-0 1.74E-0 3.86E-03 1.68E-0 10.66 1.43 at 9
Table S6: Variable teperature reduced transverse and longitudinal 17 O relaxation rates of [Gd(DTTAP-bz-NH )(H O)] -, c(gd III )=46 M, ph=5.51, P =8.19 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. t / C T / K 1000/T / K -1 T 1 (Gd)/s T 1 (H O)/s T (Gd)/s T (H O)/s ln(1/t 1r ) ln(1/t r ) 5.8 79.0 3.58 3.8E-03 3.99E-03 7.85E-04 4.0E-03 11.09 14.04 1.5 85.7 3.50 4.16E-03 5.0E-03 6.68E-04 5.00E-03 10.8 14.7 19.6 9.8 3.4 5.15E-03 6.17E-03 6.47E-04 6.6E-03 10.58 14.34 9.1 30.3 3.31 6.63E-03 7.95E-03 7.1E-04 7.95E-03 10.33 14.6 39. 31.4 3.0 8.60E-03 1.0E-0 9.70E-04 1.03E-0 9.99 13.95 45.9 319.1 3.13 9.95E-03 1.16E-0 1.9E-03 1.16E-0 9.76 13.65 55.4 38.6 3.04 1.0E-0 1.39E-0 1.77E-03 1.39E-0 9.58 13.31 59.9 333.1 3.00 1.30E-0 1.51E-0.14E-03 1.50E-0 9.49 13.10 64.5 337.7.96 1.40E-0 1.64E-0.56E-03 1.63E-0 9.47 1.90 75.4 348.6.87 1.70E-0 1.95E-0 4.10E-03 1.94E-0 9.1 1.37 85.7 358.9.79 1.96E-0.5E-0 5.9E-03.5E-0 8.99 11.93 Table S7: Variable teperature reduced transverse and longitudinal 17 O relaxation rates of [Gd(DTTAP-bz-NO )(H O)] -, c(gd III )=3 M, ph=5.91, P =5.73 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. t / C T / K 1000/T / K -1 T 1 (Gd)/s T 1 (H O)/s T (Gd)/s T (H O)/s ln(1/t 1r ) ln(1/t r ) 5.8 79.0 3.58 3.43E-03 3.99E-03 1.07E-03 4.0E-03 11.16 13.99 1.5 85.7 3.50 4.39E-03 5.0E-03 9.4E-04 5.00E-03 10.81 14.5 19.6 9.8 3.4 5.39E-03 6.17E-03 8.37E-04 6.6E-03 10.63 14.41 9.1 30.3 3.31 6.93E-03 7.95E-03 9.13E-04 7.95E-03 10.38 14.34 39. 31.4 3.0 8.95E-03 1.0E-0 1.0E-03 1.03E-0 10.05 14.07 45.9 319.1 3.13 1.0E-0 1.16E-0 1.50E-03 1.16E-0 9.93 13.83 55.4 38.6 3.04 1.4E-0 1.39E-0.09E-03 1.39E-0 9.63 13.47 59.9 333.1 3.00 1.35E-0 1.51E-0.45E-03 1.50E-0 9.53 13.30 64.5 337.7.96 1.46E-0 1.64E-0 3.0E-03 1.63E-0 9.47 13.06 75.4 348.6.87 1.75E-0 1.95E-0 4.63E-03 1.94E-0 9.0 1.57 85.7 358.9.79.04E-0.5E-0 6.66E-03.5E-0 9.01 1.13 10
Table S8. Calculation of the nuber of chelating groups per dendrier. G5-(Gd(DTTAP)) 63 n = nuber of ols of chelate per gra of product 9.89 10-4 obtained fro coplexoetric titration Total percentage of C obtained fro 48.9 eleental analysis Percentage of carbon in the chelate 4.9 (DTTAP-bz-NCS = C 1 H 9 N 4 O 10 S) calculated fro n Percentage of carbon in PAMAM skeleton 48.9-4.9 = 4.0 Forula of PAMAM skeleton G5-(NH ) 18 C 16 H 58 N 506 O 5 x = nuber of chelate bound on the dendrier 63 Percentage of substituted aino groups 49% Total percentage of N calculated by using x 16.6 Total percentage of N obtained by eleental analysis 17.3 Total percentage of S calculated by using x 3.1 Total percentage of S obtained by eleental analysis.8 Total percentage of P calculated by using x 3.0 Total percentage of P obtained by eleental analysis.7 Figure S1. Variable teperature reduced 17 O cheical shifts of [Gd(DTTAP-bz-NO )(H O)] -, c(gd III )=3 M, ph=5.91, P =5.73 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. x10 5 1x10 5 0-1x10 5 -x10 5 ω r / rad s -1-3x10 5-4x10 5-5x10 5-6x10 5-7x10 5-8x10 5.8 3.0 3. 3.4 3.6 1000/T / K -1 11
Figure S. Variable teperature reduced 17 O cheical shifts of [Gd(DTTAP-bz-NH )(H O)] -, c(gd III )=46 M, ph=5.51, P =8.19 10-4 at 9.4 T. Reference was acidified H O, ph=3.3. x10 5 1x10 5 0-1x10 5 ω r / rad s -1 -x10 5-3x10 5-4x10 5-5x10 5-6x10 5-7x10 5-8x10 5.8 3.0 3. 3.4 3.6 1000/T / K -1 Figure S3. Variable teperature reduced 17 O cheical shifts of G5-(Gd(DTTAP)) 63, c(gd III )=39 M, ph=5.69, P =7.95 10-4 at 4.7 T ( ) and 9.4 T ( ). Reference was G5-(Y(DTTAP)) 63, c(y III )=34 M, ph=5.83. x10 5 1x10 5 0 ω r / rad s -1-1x10 5 -x10 5-3x10 5-4x10 5-5x10 5-6x10 5.8.9 3.0 3.1 3. 3.3 3.4 3.5 3.6 3.7 1000/T / K -1 1
Table S9. Fitted paraeters of G5-(Gd(DTTAP)) 63. The underlined paraeters were fixed during the fitting. Paraeter G5-(Gd(DTTAP)) 63 k 98 ex [10 6 s -1 ] 5.0±0. ΔH [kj ol -1 ] 56.±1.0 ΔS [J ol -1 K -1 ] +71.9±3 A/ħ [10 6 rad s -1 ] -3.8 τ 98 go [ps] 4417±340 Ε go [kj ol -1 ] 1± τ 98 lo [ps] 71±3 Ε lo [kj ol -1 ] 1± S 0.8±0.01 τ 98 V [ps] 1± Ε V [kj ol -1 ] 5.5±5.4 Δ [10 0 s - ] 0.6±0.11 δg L [10 - ] 1.7±0.1 r GdO [Å].5 r GdHouter [Å] 3.5 χ(1+η /3) 1/ [MHz] 7.58 q 1 q nd 98 τ M nd [ps] 50 ΔH nd [kj ol -1 ] 35.0 r nd GdH [Å] 3.5 r nd GdO [Å] 4.1 13
Table S10. Fitted paraeters of [Gd(DTTAP-bz-NO )(H O)] - and [Gd(DTTAP-bz-NH )(H O)] -. The underlined paraeters were fixed during the fitting. Paraeter [Gd(DTTAP-bz-NH )(H O)] - [Gd(DTTAP-bz-NO )(H O)] - k 98 ex [10 6 s -1 ] 8.9±1.3 8.3±0.6 ΔH [kj ol -1 ] 48.1±3 48.5± ΔS [J ol -1 K -1 ] +49.8±10 +50.3±8 A/ħ [10 6 rad s -1 ] -3.8-3.8 τ 98 RO [ps] 116± 117±10 Ε R [kj ol -1 ] 0.5±0.8 18±1 τ 98 V [ps] 8.±0.5 6.3±0.4 Ε V [kj ol -1 ] 1 1 Δ [10 0 s - ] 0.403±0.003 0.40±0.01 D 98 GdH [10-10 s -1 ] 5± 5± Ε DGdH [kj ol -1 ] 30±1 30±1 δg L [10 - ] 3.3±0.6.8±0.5 τ 98 98 RH / τ RO 0.81±0.04 0.85±0.08 r GdO [Å].5.5 r GdH [Å] 3.1 3.1 r GdHouter [Å] 3.5 3.5 χ(1+η /3) 1/ [MHz] 7.58 7.58 q 1 1 q nd 98 τ M nd [ps] 50 50 ΔH nd [kj ol -1 ] 35.0 35.0 r nd GdH [Å] 3.5 3.5 r nd GdO [Å] 4.1 4.1 References for equations. 1 T. J. Swift, R. E. Connick, J. Che. Phys., 196, 37, 307. J. R. Zierann, W. E. Brittin, J. Phys. Che., 1957, 61, 138. 3 G. Lipari, S. Szabó, J. A. Che. Soc., 198, 104, 4546. 4 G. Lipari, S. Szabó, J. A. Che. Soc., 198, 104, 4559. 5 Z. Luz, S. Meiboo, J. Che. Phys., 1964, 40, 686. 6 J. H. Freed, J. Che. Phys., 1978, 68, 4034. 7 S. H. Koenig, R. D. Brown III, Prog. Nucl. Magn. Reson. Spectrosc., 1991,, 487. 14