SUPPLEMENTARY MATERIAL - CSIRO Publishing · 10.1071/CH17334_AC CSIRO 2018 Australian Journal of Chemistry 2018, 71(2 & 3), 81-86 SUPPLEMENTARY MATERIAL A Novel Strategy to Introduce

10.1071/CH17334_AC

CSIRO 2018

Australian Journal of Chemistry 2018, 71(2 & 3), 81-86

SUPPLEMENTARY MATERIAL

A Novel Strategy to Introduce 18F Positron Emitting Radionuclide in Gallium Nitrate

Complex: Synthesis, NMR, X-Ray Crystal Structure, and Preliminary Studies on

Radiolabelling with 18F

Taracad K. Venkatachalam,A,C Paul V. Bernhardt,B Damion H. R. Stimson,A Gregory K.

Pierens,A Rajiv Bhalla,A and David C. ReutensA

ACenter for Advanced Imaging, The University of Queensland, Brisbane, Qld 4072, Australia. BSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld

4072, Australia. CCorresponding author. Email: [email protected]

Table S1: Crystal parameters for compound 2

Identification code 1704v4

Empirical formula C20 H22 Ga N7 O3 S2.C4 H8 O

Formula weight 614.39

Temperature 190(2) K

Wavelength 0.71073 Å

Crystal system Triclinic

Space group P1

Unit cell dimensions a = 9.6254(8) Å = 91.738(7)°.

b = 10.5932(8) Å = 104.572(7)°.

c = 14.1321(13) Å = 91.280(6)°.

Volume 1393.3(2) Å3

Z 2

Density (calculated) 1.464 Mg/m3

Absorption coefficient 1.181 mm-1

F(000) 636

Crystal size 0.5 x 0.2 x 0.2 mm3

Theta range for data collection 3.45 to 25.00°.

Index ranges -11<=h<=8, -12<=k<=12, -16<=l<=16

Reflections collected 9328

Independent reflections 4900 [R(int) = 0.0338]

Completeness to theta = 25.00° 99.7 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 1 and 0.95931

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 4900 / 0 / 343

Goodness-of-fit on F2 1.033

Final R indices [I>2sigma(I)] R1 = 0.0413, wR2 = 0.0885

R indices (all data) R1 = 0.0558, wR2 = 0.0972

Largest diff. peak and hole 0.366 and -0.310 e.Å-3

Table S2: Selected bond lengths (Å) for Compound 2

N(2)-N(3) 1.365(3) N(3)-Ga(1) 2.037(3) N(4)- N(5) 1.370(3) N(4)-Ga(1) 2.056(2) N(7)-O(3) 1.212(3) N(7)-O(2) 1.231(4) N(7)-O(1) 1.312(3) O(1)-Ga(1) 2.2808(9) S(1)-Ga(1) 2.2808(9) S(2)-Ga(1) 2.2874(9)

Table S3. Selected bond angles (˚) for Compound 2

C(2)-N(3)-Ga(1) 118.1(2) N(2)-N(3)-Ga(1) 120.89(16) C(3)-N(4)-N(5) 120.9(3) C(3)-N(4)-Ga(1) 117.48(19) N(5)-N(4)-Ga(1) 121.12(19) C(4)-N(5)-N(4) 111.7(2) C(4)-N(6)-C(15) 130.6(3) O(3)-N(7)-O(2) 124.1(3) O(3)-N(7)-O(1) 117.3(3) O(2)-N(7)-O(1) 118.6(3) N(7)-O(1)-Ga(1) 116.7(2) C(21)-O(4)-C(24) 106.9(4) C(1)-S(1)-Ga(1) 94.62(11) C(4)-S(2)-Ga(1) 94.65(10) O(1)-Ga(1)-N(3) 93.04(9) O(1)-Ga(1)-N(4) 90.53(9) N(3)-Ga(1)-N(4) 75.82(10) O(1)-Ga(1)-S(1) 107.02(7) N(3)-Ga(1)-S(1) 83.69(8) N(4)-Ga(1)-S(1) 153.73(7) O(1)-Ga(1)-S(2) 108.89(7) N(3)-Ga(1)-S(2) 149.31(7) N(4)-Ga(1)-S(2) 82.60(7) S(1)-Ga(1)-S(2) 108.84(3)

Crystal packing diagram for symmetrical diethyl diphenyl dithiosemicarbazone gallium nitrate

(Compound 2)

Table S4. Crystal data and structure refinement for Compound 4

Identification code 1710v10

Empirical formula C19 H20 F Ga N6 S2

Formula weight 485.25

Temperature 190(2) K

Wavelength 0.71073 Å

Crystal system Monoclinic

Space group P21/n

Unit cell dimensions a = 12.8771(8) Å = 90°.

b = 12.0711(7) Å = 115.102(8)°.

c = 14.9367(12) Å = 90°.

Volume 2102.5(2) Å3

Z 4

Density (calculated) 1.533 Mg/m3

Absorption coefficient 1.534 mm-1

F(000) 992

Crystal size 0.2 x 0.1 x 0.1 mm3

Theta range for data collection 3.23 to 25.00°.

Index ranges -13<=h<=15, -14<=k<=14, -17<=l<=17

Reflections collected 8950

Independent reflections 3688 [R(int) = 0.0667]

Completeness to theta = 25.00° 99.8 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 1 and 0.98401

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 3688 / 0 / 264

Goodness-of-fit on F2 1.047

Final R indices [I>2sigma(I)] R1 = 0.0651, wR2 = 0.1214

R indices (all data) R1 = 0.1119, wR2 = 0.1408

Largest diff. peak and hole 0.649 and -0.477 e.Å-3

Table S5. Bond lengths [Å] and angles [°] for compound 4.

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C(1)-N(2) 1.304(6)

C(1)-N(1) 1.364(6)

C(1)-S(1) 1.765(6)

C(2)-N(3) 1.290(7)

C(2)-C(3) 1.467(7)

C(2)-C(5) 1.530(8)

C(3)-N(4) 1.283(7)

C(3)-C(6) 1.502(7)

C(4)-N(5) 1.313(7)

C(4)-N(6) 1.349(7)

C(4)-S(2) 1.753(6)

C(6)-C(7) 1.508(10)

C(8)-C(13) 1.370(7)

C(8)-C(9) 1.396(7)

C(8)-N(1) 1.407(7)

C(9)-C(10) 1.367(8)

C(10)-C(11) 1.349(8)

C(11)-C(12) 1.387(8)

C(12)-C(13) 1.376(8)

C(14)-C(15) 1.382(8)

C(14)-C(19) 1.391(8)

C(14)-N(6) 1.430(6)

C(15)-C(16) 1.397(7)

C(16)-C(17) 1.356(8)

C(17)-C(18) 1.382(9)

C(18)-C(19) 1.387(7)

N(2)-N(3) 1.382(6)

N(3)-Ga(1) 2.042(5)

N(4)-N(5) 1.364(6)

N(4)-Ga(1) 2.035(4)

F(1)-Ga(1) 1.948(3)

S(1)-Ga(1) 2.2984(14)

S(2)-Ga(1) 2.2911(18)

N(2)-C(1)-N(1) 120.2(5)

N(2)-C(1)-S(1) 127.1(4)

N(1)-C(1)-S(1) 112.7(4)

N(3)-C(2)-C(3) 113.4(5)

N(3)-C(2)-C(5) 124.2(5)

C(3)-C(2)-C(5) 122.2(5)

N(4)-C(3)-C(2) 114.3(5)

N(4)-C(3)-C(6) 123.2(5)

C(2)-C(3)-C(6) 122.4(6)

N(5)-C(4)-N(6) 119.9(5)

N(5)-C(4)-S(2) 126.6(5)

N(6)-C(4)-S(2) 113.5(5)

C(3)-C(6)-C(7) 112.6(6)

C(13)-C(8)-C(9) 119.5(5)

C(13)-C(8)-N(1) 124.9(5)

C(9)-C(8)-N(1) 115.6(5)

C(10)-C(9)-C(8) 119.9(6)

C(11)-C(10)-C(9) 120.9(6)

C(10)-C(11)-C(12) 119.6(6)

C(13)-C(12)-C(11) 120.6(6)

C(8)-C(13)-C(12) 119.6(5)

C(15)-C(14)-C(19) 120.1(5)

C(15)-C(14)-N(6) 124.5(5)

C(19)-C(14)-N(6) 115.3(5)

C(14)-C(15)-C(16) 118.4(6)

C(17)-C(16)-C(15) 122.0(6)

C(16)-C(17)-C(18) 119.5(6)

C(17)-C(18)-C(19) 120.0(6)

C(18)-C(19)-C(14) 120.0(6)

C(1)-N(1)-C(8) 131.2(5)

C(1)-N(2)-N(3) 111.4(4)

C(2)-N(3)-N(2) 121.4(5)

C(2)-N(3)-Ga(1) 116.9(4)

N(2)-N(3)-Ga(1) 121.5(3)

C(3)-N(4)-N(5) 120.9(5)

C(3)-N(4)-Ga(1) 117.1(4)

N(5)-N(4)-Ga(1) 121.9(4)

C(4)-N(5)-N(4) 112.3(5)

C(4)-N(6)-C(14) 130.1(5)

C(1)-S(1)-Ga(1) 94.32(18)

C(4)-S(2)-Ga(1) 94.5(2)

F(1)-Ga(1)-N(4) 102.67(15)

F(1)-Ga(1)-N(3) 99.97(17)

N(4)-Ga(1)-N(3) 75.92(18)

F(1)-Ga(1)-S(2) 105.08(11)

N(4)-Ga(1)-S(2) 83.24(15)

N(3)-Ga(1)-S(2) 150.34(14)

F(1)-Ga(1)-S(1) 106.69(9)

N(4)-Ga(1)-S(1) 146.23(14)

N(3)-Ga(1)-S(1) 82.84(13)

S(2)-Ga(1)-S(1) 104.50(6)

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1H NMR spectrum of Compound 1 in d6-DMSO

1HNMR compound 2 in d6-DMSO.

Overlay of 1H NMR of (1) starting symmetrical diethyl diphenyl dithiosemicarbazone gallium

nitrate (Compound 2) and (2) 19F exchanged symmetrical diethyl diphenyl dithiosemicarbazone

gallium fluoride complex (Note the change in the chemical shift values for the NH and one of the

ortho protons of the phenyl ring. Other tall peaks are due to residual methanol/H2O solvent

signals.)

1H NMR spectrum of 19F exchanged with compound 2.

Radio HPLC of exchange of nitrate complex of symmetrical diethyl diphenyl dithiosemicarbazone gallium (Compound 2) to the corresponding 18F complex (note: the peak at 22.5 minutes represents the radiolabeled product.

HPLC profile for UV trace during exchange reaction of nitrate to 18F in gallium complex. (the UV peak of the 18F substituted compound is buried under the nitrate compound at 22.5 minutes).

Radio and UV trace after exchange with 18F (the largest peak at 2 minutes is due to free 18F-

HPLC radio chromatogram for exchange of 18F with unsymmetrical methyl-ethyl-diphenyl-

dithiosemicarbazone nitrate complex (Compound 1).

ORTEP View of compound 2

ESI Mass spec compound 4