Crystal structure of aqua­(2-{[2-({2-[bis­(carboxyl­ato-κO-meth­yl)amino-κN]eth­yl}(carboxyl­ato-κO-meth­yl)amino-κN)eth­yl](carb­oxy­meth­yl)aza­niumyl}acetato)­gallium(III) trihydrate

Wallin, M.; Turner, P.; Katsifis, A.; Yang, M.; Chan, H.-K.

doi:10.1107/S2056989018009428

research communications

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 74| Part 8| August 2018| Pages 1054-1057

https://doi.org/10.1107/S2056989018009428

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Crystal structure of aqua(2-{[2-({2-[bis(carboxylato-κO-methyl)amino-κN]ethyl}(carboxylato-κO-methyl)amino-κN)ethyl](carboxymethyl)azaniumyl}acetato)gallium(III) trihydrate

Martin Wallin,^a Peter Turner,^b ^* Andrew Katsifis,^c Mingshi Yang ^d and Hak-Kim Chan ^a ^*

^aAdvanced Drug Delivery Group, School of Pharmacy, University of Sydney, NSW, 2006, Australia, ^bSchool of Chemistry, University of Sydney, NSW 2006, Australia, ^cDepartment of PET & Nuclear Medicine, Royal Prince Alfred Hospital, NSW 2050, Australia, and ^dDepartment of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark
^*Correspondence e-mail: peter.turner@sydney.edu.au, kim.chan@sydney.edu.au

Edited by H. Ishida, Okayama University, Japan (Received 5 June 2018; accepted 30 June 2018; online 6 July 2018)

In the title Ga^III complex compound with pentetic acid, [Ga(C₁₄H₂₀N₃O₁₀)(H₂O)]·3H₂O, the Ga^III centre is bound in a slightly distorted octahedral coordination sphere by two amine N atoms, three carboxylate O atoms and one water O atom. The complex molecule exists as a zwitterion. In the crystal, the complexes are linked to each other via O—H⋯O and C—H⋯O hydrogen bonds, forming layers parallel to (001). Three uncoordinating water molecules link the complex layers via O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional network.

Keywords: crystal structure; gallium radioisotopes; chelating agents; pentetic acid; DTPA.

CCDC reference: 1852608

1. Chemical context

The use of gallium-68 (⁶⁸Ga) for molecular imaging of diseases has become increasingly popular and the number of ⁶⁸Ga-related articles has increased drastically in the past 10 years, as pointed out by Velikyan (2014 ). The application span is wide and covers the diagnosis of cancer, cardiovascular disease, infection and inflammatory conditions (Brasse & Nonat, 2015 ; Jalilian & Akhlaghi, 2013 ; Banerjee & Pomper, 2013 ; Schultz et al., 2013 ). The increase in popularity and use can be ascribed to several factors. On the one hand, ⁶⁸Ga produces high-quality PET images. On the other hand, it has a half-life of 68 min, which makes it suitable for use in patients as the radiation dose can be kept at a minimum (Hofman & Hicks, 2016 ). ⁶⁸Ga can be eluted from a ⁶⁸Ge/⁶⁸Ga generator multiple times a day, which makes it easy for hospitals to prepare gallium solutions for patients on demand. It is vital that gallium ions are complexed, as free ions may cause undesirable effects in vivo. First, free gallium can cause iron release from transferrin, which may cause free-radical toxicity. Second, gallium ions may cause an additional and unnecessary radiation dose. 2-(Bis{2-[bis(carboxymethyl)amino]ethyl}amino)acetic acid (pentetic acid or DTPA) is an amino-polycarboxylic acid consisting of a diethylenetriamine backbone with five carboxy groups. A complex is easily formed between gallium and DTPA and it has a stability constant of 10^23.32, which makes the complex stable against exchange with transferrin (Moerlein & Welch, 1981 ; Green & Welch, 1989 ). DTPA-peptides labelled with ⁶⁸Ga have been used for liver-function imaging, determination of low-density lipoprotein metabolism, bone-marrow function and molecular identification of metastatic tumours (Haubner et al., 2013 ; Moerlein et al., 1991 ; Vera et al., 2012 ; Pitalúa-Cortés et al., 2017 ), but the molecular structure of our compound has not yet been reported. Here we present and describe the molecular structure of the title compound (Fig. 1).

Figure 1
OLEX2 generated depiction of the title compound, with displacement ellipsoids drawn at the 75% probability level. Dashed lines show O—H⋯O and N—H⋯O hydrogen bonds.

2. Structural commentary

The complex molecule (abbreviated as Ga-DTPA) is a zwitterion and has a slightly distorted octahedral coordination geometry with one water and one amine in the axial positions, and three carboxylate groups and one amine in the equatorial positions. The complex consists of three five-membered Ga/N/C/C/O chelate rings and one five-membered Ga/N/C/C/N chelate ring. The Ga—N bonds [Ga1—N1 = 2.081 (4) Å and Ga1—N2 = 2.156 (3) Å] are significantly longer than the Ga—O bonds [Ga1—O1 = 1.933 (3) Å, Ga1—O3 = 1.925 (3) Å, Ga1—O5 = 1.964 (3) Å and Ga1—O1W = 1.916 (3) Å]. The C—O bond lengths coordinating to the Ga^III atom vary little, with the shortest and longest bonds differing by only 0.019 Å [C2—O1 = 1.286 (5) Å, C4—O3 = 1.305 (5) Å and C8—O5 = 1.293 (5) Å]. The three trans angles, N1—Ga1—O1W, O1—Ga1—O5 and O3—Ga1—N2, are 174.57 (16), 174.05 (12) and 164.97 (13)°, respectively. The O—Ga—O, O—Ga—N and N—Ga—N bite angles in the chelate rings deviate somewhat from 90°, ranging from 81.75 (12) to 95.91 (12)°.

3. Supramolecular features

Packing depictions viewed along the a and b axes provided in Figs. 2 and 3, respectively, show pairs of layers containing the complexes parallel to the (001) plane. In the layer, the complexes are linked to each other by O—H⋯O and C—H⋯O hydrogen bonds (Table 1). Three uncoordinating water molecules link the complex layers via O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional network.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O10—H10O⋯O8ⁱ	0.87 (6)	1.67 (6)	2.525 (4)	169 (6)
O1W—H1WA⋯O6ⁱⁱ	0.71 (5)	1.93 (5)	2.636 (5)	174 (6)
O1W—H1WB⋯O7ⁱⁱⁱ	0.99 (6)	1.54 (6)	2.524 (5)	174 (5)
O2W—H2WA⋯O3W	0.84 (7)	1.94 (7)	2.741 (5)	158 (6)
O2W—H2WB⋯O4W	0.77 (6)	2.09 (6)	2.828 (5)	160 (6)
O3W—H3WA⋯O2ⁱ	0.79 (10)	2.47 (10)	2.934 (5)	119 (9)
O3W—H3WA⋯O10^iv	0.79 (10)	2.37 (10)	3.096 (5)	153 (9)
O3W—H3WB⋯O8^v	0.81 (7)	2.60 (6)	3.215 (5)	134 (5)
O3W—H3WB⋯O9^v	0.81 (7)	2.28 (6)	2.934 (5)	138 (6)
O4W—H4WA⋯O2	0.80 (6)	2.00 (6)	2.806 (5)	175 (6)
O4W—H4WB⋯O9^v	0.83 (7)	2.09 (7)	2.911 (5)	168 (7)
N3—H3N⋯O2W	0.90 (5)	1.91 (5)	2.737 (5)	152 (4)
C1—H1A⋯O4W^vi	0.99	2.43	3.417 (6)	173
C3—H3A⋯O7^vii	0.99	2.25	3.197 (5)	159
C3—H3B⋯O10^viii	0.99	2.52	3.225 (5)	128
C6—H6B⋯O3W	0.99	2.53	3.254 (5)	130
C7—H7B⋯O3ⁱ	0.99	2.28	3.227 (5)	161
C9—H9B⋯O8	0.99	2.53	3.207 (5)	126
C10—H10A⋯O6^ix	0.99	2.46	3.271 (5)	139
C10—H10B⋯O1ⁱ	0.99	2.53	3.300 (5)	134
C11—H11A⋯O4^x	0.99	2.45	3.438 (5)	176
C13—H13A⋯O1ⁱ	0.99	2.54	3.367 (5)	140
C13—H13A⋯O2ⁱ	0.99	2.41	3.368 (5)	162
C13—H13B⋯O6^ix	0.99	2.34	3.150 (5)	139
Symmetry codes: (i) x-1, y, z; (ii) $[-x+1, y+{\script{1\over 2}}, -z]$ ; (iii) $[-x+1, y-{\script{1\over 2}}, -z]$ ; (iv) $[-x, y-{\script{1\over 2}}, -z+1]$ ; (v) $[-x+1, y-{\script{1\over 2}}, -z+1]$ ; (vi) $[-x+2, y-{\script{1\over 2}}, -z+1]$ ; (vii) x, y-1, z; (viii) x+1, y-1, z; (ix) $[-x, y+{\script{1\over 2}}, -z]$ ; (x) x-1, y+1, z.

Figure 2
A packing diagram of the title compound, viewed along the a axis. Dashed lines show O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds.

Figure 3
A packing diagram of the title compound, viewed along the b axis. Dashed lines show O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds.

4. Database survey

In our survey of the Cambridge Structural Database (CSD version 5.39, update November 2017; Groom et al., 2016 ), we found 64 crystal structures of metal complexes with DTPA. In another search, we found 72 crystal structures of gallium complexes hexa-coordinated by two N and four O atoms.

5. Synthesis and crystallization

DTPA (50 mg) in acetate buffer (2 mL) adjusted to pH = 4.2 was heated with stirring for dissolution. Gallium nitrate (39.9 mg) was then added to the DTPA solution and the mixture was stirred for at least 10 min at 353 K. The solution was concentrated under ambient pressure at room temperature. When almost all of the solvent had evaporated, methanol was added dropwise to precipitate Ga-DTPA. The precipitate was collected on a 0.22 µm polyamide filter and dried at room temperature. The obtained Ga-DTPA (1.30 mg) was re-dissolved in ultra-pure water (1 mL) and single crystals suitable for X-ray diffraction were obtained after four weeks by slow diffusion of tetrahydrofuran into the aqueous solution, as illustrated in Fig. 4.

Figure 4
Vapor liquid diffusion technique illustration. (a) a HPLC vial containing Ga-DTPA dissolved in water was placed inside a bigger vial. The closed bigger vial contained THF. (b) THF diffused slowly into the small vial. After four weeks, visible Ga-DTPA crystals were formed.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. N- and O-bound H atoms were located in difference-Fourier maps and freely refined. C-bound H atoms were positioned geometrically (C—H = 0.99 Å) and refined using a riding model with U_iso(H) = 1.2U_eq(C).

Table 2
Experimental details

Crystal data
Chemical formula	[Ga(C₁₄H₂₀N₃O₁₀)(H₂O)]·3H₂O
M_r	532.11
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	100
a, b, c (Å)	7.1477 (2), 11.0616 (3), 13.3460 (4)
β (°)	104.929 (3)
V (Å³)	1019.58 (5)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	1.43
Crystal size (mm)	0.13 × 0.06 × 0.03

Data collection
Diffractometer	Oxford Diffraction SuperNova Dual Source diffractometer with an Atlas detector
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2015 $[Rigaku OD (2015). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.915, 1.00
No. of measured, independent and observed [I > 2σ(I)] reflections	23585, 6213, 5124
R_int	0.073
(sin θ/λ)_max (Å⁻¹)	0.714

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.073, 1.05
No. of reflections	6213
No. of parameters	329
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.73, −0.44
Absolute structure	Flack x determined using 2002 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	−0.009 (7)
Computer programs: CrysAlis PRO (Rigaku OOD, 2015 $[Rigaku OD (2015). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL2018 (Sheldrick, 2015b ), OLEX2 (Dolomanov et al., 2009 ), WinGX (Farrugia, 2012 ).

Supporting information

CCDC reference: 1852608

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989018009428/is5497sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989018009428/is5497Isup2.hkl

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OOD, 2015); cell refinement: CrysAlis PRO (Rigaku OOD, 2015); data reduction: CrysAlis PRO (Rigaku OOD, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: WinGX (Farrugia, 2012).

Aqua(2-{[2-({2-[bis(carboxylato-κO-methyl)amino-κN]ethyl}(carboxylato-κO-methyl)amino-κN)ethyl](carboxymethyl)azaniumyl}acetato)gallium(III) trihydrate top

Crystal data top

[Ga(C₁₄H₂₀N₃O₁₀)(H₂O)]·3H₂O	F(000) = 552
M_r = 532.11	D_x = 1.733 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 5696 reflections
a = 7.1477 (2) Å	θ = 3.7–28.0°
b = 11.0616 (3) Å	µ = 1.43 mm⁻¹
c = 13.3460 (4) Å	T = 100 K
β = 104.929 (3)°	Blade, colourless
V = 1019.58 (5) Å³	0.13 × 0.06 × 0.03 mm
Z = 2

Data collection top

Oxford Diffraction SuperNova Dual Source diffractometer with an Atlas detector	6213 independent reflections
Radiation source: micro-focus sealed X-ray tube	5124 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.073
Detector resolution: 10.5861 pixels mm^-1	θ_max = 30.5°, θ_min = 3.2°
ω scans	h = −10→10
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2015)	k = −15→15
T_min = 0.915, T_max = 1.00	l = −19→19
23585 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.044	w = 1/[σ²(F_o²) + (0.02P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.073	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.73 e Å⁻³
6213 reflections	Δρ_min = −0.44 e Å⁻³
329 parameters	Absolute structure: Flack x determined using 2002 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: −0.009 (7)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Ga1	0.67818 (6)	0.35920 (4)	0.14406 (3)	0.00910 (10)
C1	0.8057 (6)	0.3244 (4)	0.3657 (3)	0.0126 (9)
H1A	0.919556	0.274628	0.399527	0.015*
H1B	0.729278	0.337981	0.416943	0.015*
O1	0.8169 (4)	0.4789 (3)	0.2405 (2)	0.0112 (6)
O2	0.9839 (4)	0.5070 (3)	0.4037 (2)	0.0192 (7)
C2	0.8752 (6)	0.4454 (4)	0.3358 (3)	0.0119 (9)
O3	0.9021 (4)	0.2641 (3)	0.1407 (2)	0.0143 (7)
C3	0.7772 (6)	0.1419 (4)	0.2575 (3)	0.0143 (9)
H3A	0.676921	0.084101	0.220995	0.017*
H3B	0.844674	0.105973	0.325046	0.017*
O4	1.0435 (5)	0.0862 (3)	0.1905 (3)	0.0312 (9)
C4	0.9226 (6)	0.1631 (4)	0.1929 (4)	0.0164 (10)
O5	0.5143 (4)	0.2406 (3)	0.0522 (2)	0.0101 (6)
C5	0.4793 (6)	0.2422 (4)	0.2793 (3)	0.0120 (9)
H5A	0.474766	0.213062	0.348815	0.014*
H5B	0.413340	0.181905	0.227326	0.014*
O6	0.2129 (4)	0.1952 (3)	−0.0352 (2)	0.0132 (6)
C6	0.3768 (5)	0.3630 (5)	0.2572 (3)	0.0113 (7)
H6A	0.237081	0.351202	0.251339	0.014*
H6B	0.428383	0.418161	0.316320	0.014*
O7	0.5490 (4)	0.9137 (3)	0.1386 (2)	0.0133 (6)
C7	0.2595 (5)	0.3761 (4)	0.0650 (3)	0.0086 (9)
H7A	0.237373	0.439360	0.010694	0.010*
H7B	0.134525	0.359646	0.081351	0.010*
O8	0.5857 (4)	0.7981 (3)	0.2800 (2)	0.0120 (6)
C8	0.3304 (6)	0.2617 (4)	0.0239 (3)	0.0098 (8)
O9	0.2242 (4)	0.9005 (3)	0.3733 (2)	0.0154 (7)
O10	−0.0876 (4)	0.8862 (3)	0.3686 (2)	0.0134 (7)
H10O	−0.199 (8)	0.861 (7)	0.331 (4)	0.054 (18)*
O1W	0.6862 (5)	0.4657 (3)	0.0320 (3)	0.0124 (7)
C14	0.0674 (5)	0.8541 (5)	0.3389 (3)	0.0106 (7)
C13	0.0341 (6)	0.7512 (4)	0.2622 (3)	0.0100 (8)
H13A	−0.010336	0.678992	0.293384	0.012*
H13B	−0.068191	0.773773	0.199606	0.012*
H1WA	0.717 (7)	0.527 (5)	0.037 (4)	0.013 (15)*
H1WB	0.596 (8)	0.451 (5)	−0.036 (5)	0.039 (17)*
N1	0.6840 (5)	0.2560 (3)	0.2752 (3)	0.0108 (8)
N2	0.4008 (5)	0.4211 (3)	0.1594 (3)	0.0084 (7)
N3	0.2166 (5)	0.7221 (3)	0.2324 (3)	0.0091 (7)
H3N	0.306 (7)	0.719 (4)	0.293 (4)	0.017 (13)*
C9	0.3931 (6)	0.5548 (4)	0.1691 (3)	0.0108 (8)
H9A	0.416736	0.592496	0.106217	0.013*
H9B	0.497536	0.581169	0.229345	0.013*
C10	0.1989 (6)	0.5987 (4)	0.1829 (3)	0.0115 (9)
H10A	0.103663	0.602054	0.114376	0.014*
H10B	0.150619	0.540629	0.226776	0.014*
C12	0.4880 (5)	0.8448 (4)	0.1976 (3)	0.0098 (8)
C11	0.2714 (6)	0.8182 (4)	0.1662 (3)	0.0110 (9)
H11A	0.199397	0.893211	0.171991	0.013*
H11B	0.233493	0.791951	0.092846	0.013*
O2W	0.4169 (6)	0.6478 (4)	0.4259 (3)	0.0250 (9)
H2WA	0.373 (9)	0.581 (6)	0.441 (5)	0.05 (2)*
H2WB	0.526 (9)	0.660 (6)	0.449 (5)	0.04 (2)*
O3W	0.3776 (6)	0.4191 (4)	0.4967 (3)	0.0260 (9)
H3WA	0.278 (14)	0.409 (10)	0.511 (8)	0.15 (5)*
H3WB	0.452 (9)	0.390 (6)	0.547 (5)	0.06 (2)*
O4W	0.8110 (5)	0.6367 (3)	0.5369 (3)	0.0239 (8)
H4WA	0.865 (8)	0.603 (6)	0.499 (5)	0.04 (2)*
H4WB	0.806 (9)	0.574 (7)	0.571 (5)	0.06 (2)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Ga1	0.00710 (17)	0.00922 (19)	0.01104 (19)	0.0001 (2)	0.00244 (14)	−0.0001 (2)
C1	0.014 (2)	0.013 (2)	0.009 (2)	−0.0019 (17)	−0.0004 (17)	0.0032 (16)
O1	0.0069 (14)	0.0131 (16)	0.0119 (15)	−0.0001 (12)	−0.0005 (12)	0.0006 (12)
O2	0.0205 (17)	0.0209 (18)	0.0129 (16)	−0.0102 (14)	−0.0018 (14)	−0.0009 (14)
C2	0.0083 (19)	0.014 (2)	0.014 (2)	0.0032 (17)	0.0043 (18)	0.0001 (18)
O3	0.0074 (14)	0.0141 (16)	0.0213 (17)	0.0017 (13)	0.0038 (13)	0.0035 (13)
C3	0.012 (2)	0.011 (2)	0.018 (2)	0.0029 (17)	−0.0011 (18)	0.0037 (18)
O4	0.0219 (18)	0.023 (2)	0.054 (3)	0.0120 (16)	0.0190 (18)	0.0114 (18)
C4	0.0086 (19)	0.016 (2)	0.024 (3)	−0.0025 (18)	0.0021 (19)	−0.0013 (19)
O5	0.0080 (13)	0.0093 (15)	0.0128 (15)	0.0013 (12)	0.0022 (12)	−0.0041 (12)
C5	0.0103 (19)	0.012 (2)	0.013 (2)	−0.0014 (17)	0.0031 (17)	0.0054 (17)
O6	0.0120 (14)	0.0107 (15)	0.0154 (16)	−0.0012 (12)	0.0007 (13)	−0.0020 (12)
C6	0.0110 (16)	0.0127 (18)	0.0110 (17)	0.001 (2)	0.0044 (14)	0.000 (2)
O7	0.0138 (14)	0.0143 (15)	0.0121 (15)	−0.0054 (13)	0.0039 (13)	0.0009 (12)
C7	0.0068 (16)	0.010 (2)	0.0087 (17)	−0.0003 (16)	0.0006 (14)	−0.0033 (16)
O8	0.0088 (14)	0.0130 (15)	0.0131 (15)	−0.0006 (12)	0.0009 (12)	0.0017 (12)
C8	0.0118 (19)	0.009 (2)	0.009 (2)	−0.0005 (17)	0.0037 (17)	0.0019 (16)
O9	0.0086 (13)	0.0172 (16)	0.0187 (16)	−0.0016 (12)	0.0006 (12)	−0.0037 (13)
O10	0.0080 (13)	0.018 (2)	0.0136 (15)	0.0008 (12)	0.0023 (12)	−0.0027 (12)
O1W	0.0157 (16)	0.0096 (17)	0.0120 (17)	0.0001 (14)	0.0041 (13)	0.0004 (13)
C14	0.0104 (16)	0.0093 (17)	0.0118 (17)	0.004 (2)	0.0025 (14)	0.007 (2)
C13	0.0051 (18)	0.012 (2)	0.013 (2)	0.0008 (17)	0.0033 (16)	−0.0022 (17)
N1	0.0086 (17)	0.0101 (18)	0.0131 (19)	−0.0016 (15)	0.0018 (15)	0.0001 (15)
N2	0.0074 (16)	0.0080 (17)	0.0097 (17)	0.0015 (14)	0.0021 (14)	−0.0005 (14)
N3	0.0052 (16)	0.0086 (17)	0.0129 (19)	−0.0008 (14)	0.0013 (15)	−0.0005 (14)
C9	0.0082 (19)	0.009 (2)	0.016 (2)	−0.0019 (16)	0.0042 (17)	−0.0022 (17)
C10	0.0079 (19)	0.009 (2)	0.018 (2)	−0.0036 (16)	0.0033 (17)	−0.0022 (17)
C12	0.0094 (16)	0.008 (2)	0.0131 (18)	−0.0030 (18)	0.0046 (15)	−0.0025 (18)
C11	0.0099 (19)	0.0107 (19)	0.012 (2)	0.0005 (16)	0.0029 (17)	0.0030 (16)
O2W	0.0194 (19)	0.026 (2)	0.026 (2)	−0.0052 (17)	−0.0019 (17)	0.0104 (17)
O3W	0.0217 (19)	0.033 (2)	0.021 (2)	−0.0020 (17)	0.0021 (17)	0.0110 (17)
O4W	0.0231 (19)	0.020 (2)	0.026 (2)	0.0017 (16)	0.0015 (17)	0.0028 (17)

Geometric parameters (Å, º) top

Ga1—O1W	1.916 (3)	C7—H7A	0.9900
Ga1—O3	1.925 (3)	C7—H7B	0.9900
Ga1—O1	1.933 (3)	O8—C12	1.251 (5)
Ga1—O5	1.964 (3)	O9—C14	1.211 (5)
Ga1—N1	2.081 (4)	O10—C14	1.318 (4)
Ga1—N2	2.156 (3)	O10—H10O	0.87 (6)
C1—N1	1.499 (5)	O1W—H1WA	0.71 (5)
C1—C2	1.517 (6)	O1W—H1WB	0.99 (6)
C1—H1A	0.9900	C14—C13	1.508 (6)
C1—H1B	0.9900	C13—N3	1.493 (5)
O1—C2	1.286 (5)	C13—H13A	0.9900
O2—C2	1.236 (5)	C13—H13B	0.9900
O3—C4	1.305 (5)	N2—C9	1.486 (5)
C3—N1	1.474 (5)	N3—C11	1.497 (5)
C3—C4	1.530 (6)	N3—C10	1.507 (5)
C3—H3A	0.9900	N3—H3N	0.90 (5)
C3—H3B	0.9900	C9—C10	1.526 (5)
O4—C4	1.219 (5)	C9—H9A	0.9900
O5—C8	1.293 (5)	C9—H9B	0.9900
C5—N1	1.486 (5)	C10—H10A	0.9900
C5—C6	1.516 (6)	C10—H10B	0.9900
C5—H5A	0.9900	C12—C11	1.525 (5)
C5—H5B	0.9900	C11—H11A	0.9900
O6—C8	1.236 (5)	C11—H11B	0.9900
C6—N2	1.505 (5)	O2W—H2WA	0.84 (7)
C6—H6A	0.9900	O2W—H2WB	0.77 (6)
C6—H6B	0.9900	O3W—H3WA	0.79 (10)
O7—C12	1.252 (5)	O3W—H3WB	0.81 (7)
C7—N2	1.483 (5)	O4W—H4WA	0.80 (6)
C7—C8	1.517 (6)	O4W—H4WB	0.83 (7)

O1W—Ga1—O3	97.21 (13)	O5—C8—C7	117.1 (3)
O1W—Ga1—O1	89.15 (14)	C14—O10—H10O	117 (4)
O3—Ga1—O1	95.91 (12)	Ga1—O1W—H1WA	125 (4)
O1W—Ga1—O5	93.24 (14)	Ga1—O1W—H1WB	118 (3)
O3—Ga1—O5	89.19 (12)	H1WA—O1W—H1WB	111 (5)
O1—Ga1—O5	174.05 (12)	O9—C14—O10	122.6 (4)
O1W—Ga1—N1	174.57 (16)	O9—C14—C13	123.2 (4)
O3—Ga1—N1	83.30 (14)	O10—C14—C13	114.2 (3)
O1—Ga1—N1	85.42 (13)	N3—C13—C14	110.3 (3)
O5—Ga1—N1	92.17 (13)	N3—C13—H13A	109.6
O1W—Ga1—N2	95.26 (13)	C14—C13—H13A	109.6
O3—Ga1—N2	164.97 (13)	N3—C13—H13B	109.6
O1—Ga1—N2	92.62 (12)	C14—C13—H13B	109.6
O5—Ga1—N2	81.75 (12)	H13A—C13—H13B	108.1
N1—Ga1—N2	85.08 (13)	C3—N1—C5	114.1 (3)
N1—C1—C2	113.2 (3)	C3—N1—C1	111.7 (3)
N1—C1—H1A	108.9	C5—N1—C1	113.2 (3)
C2—C1—H1A	108.9	C3—N1—Ga1	104.3 (3)
N1—C1—H1B	108.9	C5—N1—Ga1	106.3 (2)
C2—C1—H1B	108.9	C1—N1—Ga1	106.4 (2)
H1A—C1—H1B	107.7	C7—N2—C9	112.0 (3)
C2—O1—Ga1	116.2 (3)	C7—N2—C6	112.9 (3)
O2—C2—O1	123.3 (4)	C9—N2—C6	109.5 (3)
O2—C2—C1	118.6 (4)	C7—N2—Ga1	104.7 (2)
O1—C2—C1	118.0 (4)	C9—N2—Ga1	112.3 (2)
C4—O3—Ga1	115.8 (3)	C6—N2—Ga1	105.1 (2)
N1—C3—C4	111.1 (4)	C13—N3—C11	112.6 (3)
N1—C3—H3A	109.4	C13—N3—C10	109.4 (3)
C4—C3—H3A	109.4	C11—N3—C10	112.9 (3)
N1—C3—H3B	109.4	C13—N3—H3N	104 (3)
C4—C3—H3B	109.4	C11—N3—H3N	109 (3)
H3A—C3—H3B	108.0	C10—N3—H3N	108 (3)
O4—C4—O3	124.5 (4)	N2—C9—C10	112.5 (3)
O4—C4—C3	119.8 (4)	N2—C9—H9A	109.1
O3—C4—C3	115.7 (4)	C10—C9—H9A	109.1
C8—O5—Ga1	117.3 (3)	N2—C9—H9B	109.1
N1—C5—C6	109.5 (3)	C10—C9—H9B	109.1
N1—C5—H5A	109.8	H9A—C9—H9B	107.8
C6—C5—H5A	109.8	N3—C10—C9	111.5 (3)
N1—C5—H5B	109.8	N3—C10—H10A	109.3
C6—C5—H5B	109.8	C9—C10—H10A	109.3
H5A—C5—H5B	108.2	N3—C10—H10B	109.3
N2—C6—C5	112.8 (3)	C9—C10—H10B	109.3
N2—C6—H6A	109.0	H10A—C10—H10B	108.0
C5—C6—H6A	109.0	O8—C12—O7	126.7 (3)
N2—C6—H6B	109.0	O8—C12—C11	117.3 (4)
C5—C6—H6B	109.0	O7—C12—C11	115.9 (3)
H6A—C6—H6B	107.8	N3—C11—C12	112.1 (3)
N2—C7—C8	111.7 (3)	N3—C11—H11A	109.2
N2—C7—H7A	109.3	C12—C11—H11A	109.2
C8—C7—H7A	109.3	N3—C11—H11B	109.2
N2—C7—H7B	109.3	C12—C11—H11B	109.2
C8—C7—H7B	109.3	H11A—C11—H11B	107.9
H7A—C7—H7B	107.9	H2WA—O2W—H2WB	117 (6)
O6—C8—O5	123.4 (4)	H3WA—O3W—H3WB	101 (8)
O6—C8—C7	119.5 (3)	H4WA—O4W—H4WB	93 (6)

Ga1—O1—C2—O2	171.5 (3)	C2—C1—N1—C3	116.1 (4)
Ga1—O1—C2—C1	−8.7 (4)	C2—C1—N1—C5	−113.6 (4)
N1—C1—C2—O2	−176.8 (4)	C2—C1—N1—Ga1	2.9 (4)
N1—C1—C2—O1	3.5 (5)	C8—C7—N2—C9	150.0 (3)
Ga1—O3—C4—O4	172.0 (4)	C8—C7—N2—C6	−85.8 (4)
Ga1—O3—C4—C3	−5.9 (5)	C8—C7—N2—Ga1	28.0 (4)
N1—C3—C4—O4	163.3 (4)	C5—C6—N2—C7	83.8 (4)
N1—C3—C4—O3	−18.7 (5)	C5—C6—N2—C9	−150.7 (3)
N1—C5—C6—N2	51.6 (4)	C5—C6—N2—Ga1	−29.8 (4)
Ga1—O5—C8—O6	178.6 (3)	C14—C13—N3—C11	−70.5 (4)
Ga1—O5—C8—C7	−0.2 (5)	C14—C13—N3—C10	163.1 (3)
N2—C7—C8—O6	160.4 (4)	C7—N2—C9—C10	63.9 (4)
N2—C7—C8—O5	−20.7 (5)	C6—N2—C9—C10	−62.1 (4)
O9—C14—C13—N3	−3.2 (6)	Ga1—N2—C9—C10	−178.5 (3)
O10—C14—C13—N3	179.4 (3)	C13—N3—C10—C9	−169.5 (3)
C4—C3—N1—C5	146.3 (4)	C11—N3—C10—C9	64.3 (4)
C4—C3—N1—C1	−83.8 (4)	N2—C9—C10—N3	158.1 (3)
C4—C3—N1—Ga1	30.7 (4)	C13—N3—C11—C12	138.0 (4)
C6—C5—N1—C3	−158.9 (3)	C10—N3—C11—C12	−97.6 (4)
C6—C5—N1—C1	72.0 (4)	O8—C12—C11—N3	−9.5 (6)
C6—C5—N1—Ga1	−44.5 (4)	O7—C12—C11—N3	171.9 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O10—H10O···O8ⁱ	0.87 (6)	1.67 (6)	2.525 (4)	169 (6)
O1W—H1WA···O6ⁱⁱ	0.71 (5)	1.93 (5)	2.636 (5)	174 (6)
O1W—H1WB···O7ⁱⁱⁱ	0.99 (6)	1.54 (6)	2.524 (5)	174 (5)
O2W—H2WA···O3W	0.84 (7)	1.94 (7)	2.741 (5)	158 (6)
O2W—H2WB···O4W	0.77 (6)	2.09 (6)	2.828 (5)	160 (6)
O3W—H3WA···O2ⁱ	0.79 (10)	2.47 (10)	2.934 (5)	119 (9)
O3W—H3WA···O10^iv	0.79 (10)	2.37 (10)	3.096 (5)	153 (9)
O3W—H3WB···O8^v	0.81 (7)	2.60 (6)	3.215 (5)	134 (5)
O3W—H3WB···O9^v	0.81 (7)	2.28 (6)	2.934 (5)	138 (6)
O4W—H4WA···O2	0.80 (6)	2.00 (6)	2.806 (5)	175 (6)
O4W—H4WB···O9^v	0.83 (7)	2.09 (7)	2.911 (5)	168 (7)
N3—H3N···O2W	0.90 (5)	1.91 (5)	2.737 (5)	152 (4)
C1—H1A···O4W^vi	0.99	2.43	3.417 (6)	173
C3—H3A···O7^vii	0.99	2.25	3.197 (5)	159
C3—H3B···O10^viii	0.99	2.52	3.225 (5)	128
C6—H6B···O3W	0.99	2.53	3.254 (5)	130
C7—H7B···O3ⁱ	0.99	2.28	3.227 (5)	161
C9—H9B···O8	0.99	2.53	3.207 (5)	126
C10—H10A···O6^ix	0.99	2.46	3.271 (5)	139
C10—H10B···O1ⁱ	0.99	2.53	3.300 (5)	134
C11—H11A···O4^x	0.99	2.45	3.438 (5)	176
C13—H13A···O1ⁱ	0.99	2.54	3.367 (5)	140
C13—H13A···O2ⁱ	0.99	2.41	3.368 (5)	162
C13—H13B···O6^ix	0.99	2.34	3.150 (5)	139

Symmetry codes: (i) x−1, y, z; (ii) −x+1, y+1/2, −z; (iii) −x+1, y−1/2, −z; (iv) −x, y−1/2, −z+1; (v) −x+1, y−1/2, −z+1; (vi) −x+2, y−1/2, −z+1; (vii) x, y−1, z; (viii) x+1, y−1, z; (ix) −x, y+1/2, −z; (x) x−1, y+1, z.

Acknowledgements

The authors would like to thank Professor David Hibbs for his help regarding the crystal structure of Ga-DTPA. The authors would also like to thank Dr Lea Gagnon and Dr Philip Chi Lip Kwok for their editorial support. HKC is grateful to Mr Richard Stenlake for his generous financial support. Finally, the authors want to thank Dr Leo Corcilius for his input for this work.

Funding information

Funding for this research was provided by: Australian Research Council (grant No. 160102577 to Hak-Kim Chan).

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