Synthesis of bifunctional biscatecholamine chelators for uranium decorporation

Article abstract of DOI:10.1016/j.poly.2016.09.006

New 1,3-dicarbonyl biscatecholamide ligands were synthesized to decorporate uranium for nuclear contamination. The derivatives were characterized via¹H NMR spectroscopy,¹³C NMR spectroscopy, FTIR spectroscopy and mass spectrometry. The complexation abilities of ligands 8a–8d with UO₂²⁺, Cu²⁺and Zn²⁺were determined through spectrophotometric and potentiometric titrations technology. The antioxidant capacities of the ligands were assessed through DPPH antioxidant assay. Results indicated that ligands 8a–8d are potential decorporating agents for uranyl ion (pUO₂up to 22.41) and copper(II) ion (pCu up to 17.71) without depletion of the essential element zinc (pZn lower than 7.48).

Full text of DOI:10.1016/j.poly.2016.09.006

Polyhedron 119 (2016) 387–395
Contents lists available at ScienceDirect
Polyhedron
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Synthesis of bifunctional biscatecholamine chelators for uranium
decorporation
a
b
a
a,b,
a
Shan Lei a, Bo Jin a,b, , Qingchun Zhang , Zhichao Zhang , Xiaofang Wang , Rufang Peng
, Shijin Chu
⇑
⇑
a State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, Southwest University of Science and Technology, Mianyang 621010, China
b Department of Chemistry, School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 May 2016
Accepted 4 September 2016
Available online 21 September 2016
New 1,3-dicarbonyl biscatecholamide ligands were synthesized to decorporate uranium for nuclear con-
tamination. The derivatives were characterized via 1H NMR spectroscopy, 13C NMR spectroscopy, FTIR
spectroscopy and mass spectrometry. The complexation abilities of ligands 8a–8d with UO22+, Cu2+ and
Zn2+ were determined through spectrophotometric and potentiometric titrations technology. The antiox-
idant capacities of the ligands were assessed through DPPH antioxidant assay. Results indicated that
ligands 8a–8d are potential decorporating agents for uranyl ion (pUO2 up to 22.41) and copper(II) ion
(pCu up to 17.71) without depletion of the essential element zinc (pZn lower than 7.48).
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Catecholamide
Uranyl ion
Spectrophotometric titration
Complexation
Antioxidation
1. Introduction
important complexing and masking agent for metal ions [18].
Subsequently, O’Brien et al. [19] found a catechol derivative
Uranium, commonly used as a nuclear fuel and constituent of
nuclear weapons for civilian and military purposes, can be intro-
duced into the living system by ingestion, inhalation or through
wounds [1]. Hexavalent uranyl ion (UO22+, U(VI)) is the most stable
form in aqueous solutions and serum in vivo [2–4]. Uranyl ion is
mainly complexed by blood transferrin and natural low-molecu-
lar-weight complexing agents, such as citrates, bicarbonates and
phosphates [5], forming stable complexes at the physiological
pH. However, the uranyl ion complexes retained in target organs,
especially in kidneys, liver and marrow after chelation within
blood, are a source of cancer and chemical intoxication [6,7]. Fur-
thermore, the alpha particles emitted by uranium can produce free
radicals that can kill cells [8–10]. Thus, the present study aims to
find nontoxic bifunctional chelating agents that can efficiently pro-
mote the excretion of uranyl ion and scavenge free radicals.
Among the common chelating agents that have been reported
[11–16], sulfocatecholamides can chelate lanthanides efficiently.
In 1950, Lusky et al. [17] first found Tiron (disodium salt of
1,2-dihydroxybenzene-3,5-disulfonic acid), which forms a stable
U(VI) complex within a pH range of 6–8. Given its reasonably small
size and high chelating capacity, Tiron has been used as an
(Enterobactin, Scheme 1) claimed to be the most effective natural
Fe(III) ligand in vivo. The similar coordination features of iron(III)
and uranium suggest that multidentate sulfocatecholamide
(CAMS) ligands are effective for U(VI) chelation. This inference
has been confirmed by some experimental studies. Leydier et al.
[20,21] synthesized a series of sulfocatecholamides to chelate
uranyl ion, in which the association constant (logK) of CYCAMS
(N,N-bis(2,3-dihydroxy-5-sulfonylbenzoyl)cyclohexane-(1,3)-bis-
methyamine) reaches 17.5 under neutral pH.
Catecholamide exerts an antioxidative effect, which may be
related to its hydroxy and amine groups [22,23]. As a result, cate-
cholamide can be used to scavenge free radicals generated in the
human body.
1,3-Dicarbonyl compounds are important in synthetic organic
chemistry because the obtained skeletons are intermediates for
the synthesis of various biologically active compounds [24–26].
Catecholamide ligands have attracted considerable attention
because of their high affinity and potential clinical applications
as decorporation agents for heavy metal ions [27–29]. Our previous
study showed that ethylenediamine derivatives demonstrate
higher complexation capability but lower antioxidant capacity
than aminoalcohol [30]. Therefore, we investigated ligands with a
high complexation capability and antioxidant capacity, and syn-
thesized a new family of 1,3-dicarbonyl biscatecholamide ligands
through efficient synthetic routes from different backbones
(Scheme 2). Moreover, the chelating abilities of UO22+, Cu2+ (free
⇑
Corresponding authors at: State Key Laboratory Cultivation Base for Nonmetal
Composites and Functional Materials, Southwest University of Science and Tech-
nology, Mianyang 621010, China.
E-mail addresses: jinbo0428@163.com (B. Jin), rfpeng2006@163.com (R. Peng).
http://dx.doi.org/10.1016/j.poly.2016.09.006
0277-5387/Ó 2016 Elsevier Ltd. All rights reserved.

388
S. Lei et al. / Polyhedron 119 (2016) 387–395
were determined at 25.0 0.1 °C under N2 atmosphere with stir-
OH
OH
ring. Solids reagents were weighed on a Sartorius BT25S analytical
balance accurate to 0.01 mg. Titration solutions were prepared
using distilled water from Ulupure ULUP-IV ultra water system
and degassed by ultrasonic device. The 0.1 M nitrate standard solu-
tion and 0.1 M KOH standard solution were commercial products
from Aladdin. Certain amount of KCl were weighed accurately
and dissolved with water to 1 L in volumetric flasks. The ligands
stock solutions were 2 ꢂ 10ꢁ4 M while the metal ions (made from
UO2(NO3)2ꢀ6H2O, Cu(NO3)2ꢀ3H2O and Zn(NO3)2ꢀ6H2O, respectively)
stock solutions were 0.01 M. Certain amounts of the ligands 8a–8d
were weighed accurately with 1 vol% ethanol dissolved, and then
diluted with 0.1 M KCl aqueous solution to 250 mL in volumetric
flasks. And the metal ions stock solutions were obtained by certain
amounts of metal salts directly diluted with 0.1 M KCl aqueous
solution to 25 mL in volumetric flasks.
HN
O
O
O
O
O
O
OH
O
HO
O
N
H
NH
O
HO
OH
Scheme 1. Chemical structure of Enterobactin.
The protonation constants of ligands 8a–8d were performed
with 25 mL ligands, and spectrophotometric titrations [32–35]
were used with the UV–Vis spectrophotometer until no significant
changes on spectrophotometric curves. The spectrophotometric
titrations were calculated by the HypSpec 2014 program [36] to
obtain the first two protonation constants because of the limitation
of the potential titrator at a high pH. Potentiometric titrations
[37–40] were used to obtain the last two protonation constants
by the Hyperquad 2013 program [41] holding the values previ-
ously determined by spectrophotometric titrations. For the titra-
tions, the ligand concentration was 2 ꢂ 10ꢁ4 M, and the
concentrations of base (KOH) were 0.1 and 0.01 M in spectrophoto-
metric and potentiometric titrations, respectively. The stability
H2N
XH
1
NH2
H2N
NH2
H2N
1a
1c
1b
NH2
O
H2N
H2N
OH
constants of ligands 8a–8d with metal ions (UO22+, Cu2+ and Zn2+
)
1d
were all determined by spectrophotometric titrations. To a mixture
of 0.5 mL metal ions stock solutions and 1.5 mL nitrate standard
solution (0.5 mL just for ligands with Zn2+), 25 mL ligands stock
solutions were added. The UV–Vis spectra were measured from
250 to 550 nm with the KOH solution gradually adding into the
titration cup. HypSpec 2014 program were used to calculate global
formation constants (logbpqr) in the presence of global protonation
constants. All the concentration distribution curves were gener-
ated with the HySS program [42]. The UV–Vis spectra of ligands
8a–8d in the presence of metal ions and concentration distribution
curves for the complexes of ligands 8a–8d with Cu2+ and Zn2+ are
included in Supporting Information.
Scheme 2. Diamine and aminoalcohol backbones.
copper ions in body induce the damages of various biomolecules)
[31] and Zn2+ (essential trace element) were studied through spec-
trophotometric titrations. The structures of all products were char-
acterized, and their antioxidant capacities were investigated using
DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant assay.
2. Experimental
2.1. General
2.3. Antioxidant method
All the organic reagents used were pure commercial products
from Aladdin expect UO2(NO3)2ꢀ6H2O (from HuBei ChuShengWei
Chemistry Co., Ltd.). Anhydrous solvents were purchased from
Chengdu Kelong Chemical Reagents Co., Ltd. and dry CH2Cl2 was
distilled after processed with anhydrous calcium chloride
overnight and refluxed in the presence of calcium hydride for
three hours. Flash chromatography was carried out on the
300–400 mesh silica gel from Qingdao Hailang. 1H NMR, 13C NMR
spectra were recorded on Bruker Avance 300, Avance 400 or
Avance 600 spectrometer. FTIR spectra were collected from Nicolet
380 FTIR spectrophotometer (Thermo Fisher Nicolet, USA) with a
The antioxidant activities of 8a–8d were determined using
DPPH antioxidant assay, i.e., 0.2 mL of 8a–8d aqueous solution
(2 ꢂ 10ꢁ4 mol/L) or 0.2 mL of water was added to 2.8 mL of DPPH
ethanol solution (1.15 ꢂ 10ꢁ4 mol/L). The absorbance was rapidly
determined for 4000 s at 1 s intervals at 517 nm because of the
intense absorption at the wavelength.
2.4. Compounds synthesis
2.4.1. Synthesis of (2-aminobutyl)carbamic acid tert-butyl ester (2a)
Di-tert-butyl dicarbonate (3.63 g, 0.017 mol, dissolved in 10 mL
resolution of 4 cmꢁ1 from 400 cmꢁ1 to 4000 cmꢁ1
. UV–Vis
spectrophotometer (Thermo Scientific Evolution 201, USA) with a
double-beam light source from 190 nm to 1100 nm was used. Mass
spectrometry (MS) was conducted using Varian 1200 LC/MS.
methanol) was added into
a solution of diamine 1a (3.0 g,
0.05 mol) in triethylamine and methanol (10% TEA in MeOH,
110 mL), and the obtained solution was stirred at room tempera-
ture overnight. The methanol and TEA were removed in vacuo to
yield an oily residue that was dissolved in dichloromethane
(100 mL) and washed with a solution of 10% aq sodium carbonate
(2 ꢂ 100 mL). The organic layer was dried over anhydrous Na2SO4,
filtered, and evaporated to dryness to give translucent oil. The
crude product was chromatographed on silica gel (NH4OH:
MeOH:CHCl3, 1:10:89) to give 2a as yellow oils (1.91 g, 70%).
2.2. Titration Methods
Potentiometric titrations were carried out on ZDJ-4B automatic
potential titrator (Shanghai INESA Scientific Instrument Co., Ltd.).
Spectrophotometric titrations were performed using a Thermo Sci-
entific Evolution 201 UV–Vis spectrophotometer. All titrations

S. Lei et al. / Polyhedron 119 (2016) 387–395
389
Rf = 0.4. 1H NMR (600 MHz, CDCl3, 298.0 K) d (ppm): 5.01 (br s, 1H,
NH–CO), 3.17 (t, J 5.4 Hz, 2H, CH2), 2.79 (t, J 6.0 Hz, 2H, CH2), 1.71
(br s, 2H, NH2), 1.44 (s, 9H, CH3); FTIR (KBr)
FTIR (KBr)
v
(cmꢁ1): 3353, 3062, 3030, 2980, 2931, 1686, 1638,
1577, 1498, 1448, 1368, 1270, 741; APCI-MS: m/z (M+1)+ = 477.
v
(cmꢁ1): 3355,
2975, 2932, 1694, 1522, 1392, 1366, 1276, 1252, 1046; APCI-MS:
2.4.6. Synthesis of N-(N’-tert-butyloxycarbonylpropane diamino)-2,3-
bis(benzyloxy)benzamide (4b)
m/z (M+1)+ = 161.
Using the same procedure as 4a. Purification on silica gel (ace-
tone:hexane, 1:3) afforded 4b as yellow solid (86%). Rf = 0.4. 1H
NMR (300 MHz, CDCl3, 298.0 K) d (ppm): 7.97 (br s, 1H, CO–NH),
7.69 (m, 1H, Ar–H), 7.50–7.00 (m, 12H, Ar–H), 5.16 (s, 2H, O–
CH2–Ar), 5.10 (s, 2H, O–CH2–Ar), 3.29 (q, J 6.4 Hz, 2H, CH2), 3.01
(q, J 6.1 Hz, 2H, CH2), 1.51–1.43 (m, 11H, CH3 and CH2); 13C NMR
(150 MHz, CDCl3, 298.0 K) d (ppm): 165.80 (C@O), 156.20 (C@O),
151.84 (Ar–C), 146.96 (Ar–CH), 136.57 (Ar–CH), 136.57 (Ar–CH),
136.55 (Ar–CH), 128.88 (Ar–CH), 128.83 (Ar–CH), 128.81
(Ar–CH), 128.39 (Ar–CH), 127.78 (Ar–CH), 117.23 (Ar–CH), 76.57
(CH2), 71.47 (CH2), 37.54 (CH2), 36.66 (CH2), 34.08 (CH2), 30.08
2.4.2. Synthesis of (3-aminobutyl)carbamic acid tert-butyl ester (2b)
Using the same procedure as 2a. Purification on silica gel
(NH4OH:MeOH:CHCl3, 1:10:89) afforded 2b as yellow oil (72%).
Rf = 0.4. 1H NMR (600 MHz, CDCl3, 298.0 K) d (ppm): 4.94 (br s, 1H,
NH–CO), 3.14 (t, J 6.3 Hz, 2H, CH2), 2.70 (t, J 6.9 Hz, 2H, CH2), 1.55
(m, 2H, CH2), 1.37 (s, 9H, CH3); FTIR (KBr)
v
(cmꢁ1): 3368, 2931,
2875, 1652, 1538, 1453, 1375, 1265; APCI-MS: m/z (M+1)+ = 175.
2.4.3. Synthesis of (4-aminobutyl)carbamic acid tert-butyl ester (2c)
Using the same procedure as 2a. Purification on silica gel
(NH4OH:MeOH:CHCl3, 1:10:89) afforded 2c as yellow oil (75%).
Rf = 0.4. 1H NMR (600 MHz, CDCl3, 298.0 K) d (ppm): 4.82 (br s,
1H, NH–CO), 3.08 (t, J 4.2 Hz, 2H, CH2), 2.70 (t, J 6.3 Hz, 2H, CH2),
(CH2), 28.57 (CH3); FTIR (KBr)
v
(cmꢁ1): 3433, 3346, 3068, 2938,
1673, 1620, 1573, 1536, 1452, 1275, 757; APCI-MS: m/z
(M+1)+ = 491.
1.48 (m, 2H, CH2), 1.40 (m, 11H, CH3 and CH2); FTIR (KBr)
v
2.4.7. Synthesis of N-(N’-tert-butyloxycarbonylbutane diamino)-2,3-
bis(benzyloxy)benzamide (4c)
(cmꢁ1): 3388, 2944, 2870, 1701, 1648, 1518, 1452, 1366, 1270,
1058; APCI-MS: m/z (M+1)+ = 189.
Using the same procedure as 4a. Purification on silica gel (etha-
nol:CH2Cl2, 1:50) afforded 4c as yellow solid (90%). Rf = 0.5. 1H
NMR (600 MHz, CDCl3, 298.0 K) d (ppm): 7.87 (br s, 1H, CO–NH),
7.64 (m, 1H, Ar–H), 7.46–7.00 (m, 12H, Ar–H), 5.07 (s, 2H,
O–CH2–Ar), 5.00 (s, 2H, O–CH2–Ar), 3.18 (q, J 6.4 Hz, 2H, CH2),
2.94 (m, 2H, CH2), 1.36 (s, 9H, CH3), 1.26 (m, 4H, CH2); 13C NMR
(150 MHz, CDCl3, 298.0 K) d (ppm): 165.22 (C@O), 156.05 (C@O),
151.88 (Ar–C), 147.04 (Ar–CH), 136.67 (Ar–C), 136.63 (Ar–CH),
128.83 (Ar–CH), 128.81 (Ar–CH), 128.80 (Ar–CH), 128.37
(Ar–CH), 127.78 (Ar–CH), 117.27 (Ar–CH), 76.52 (CH2), 71.57
(CH2), 39.43 (CH2), 28.58 (CH3), 27.61 (CH2), 26.78 (CH2); FTIR
2.4.4. Synthesis of 2,3-bis(benzyloxy)benzoic acid (3)
Benzyl bromide (22.2 g, 130 mmol) was added into a solution of
2,3-dihydroxybenzoic acid (10.15 g, 65.86 mmol) and K2CO3
(18.0 g, 130 mmol) in acetone (200 mL), and the mixture was
refluxed for 24 h. After filtration of the reaction mixture, the sol-
vent was evaporated under reduced pressure to obtain the crude
product as clear oil. The crude product was dissolved in 200 mL
methanol, and 15.07 g LiOHꢀH2O (359.1 mmol) was slowly added
with refluxing for 3 h. Then, the solution was acidified with 3 M
HCl until ca. pH = 2 and filtered to give 3 as a white solid
(17.62 g, 80%). 1H NMR (400 MHz, CDCl3, 298.0 K) d (ppm):
7.50–7.10 (m, 12H, Ar–H), 7.03 (t, J 8.0 Hz, 1H, Ar–H), 5.12 (s, 2H,
O–CH2–Ar), 5.09 (s, 2H, O–CH2–Ar); 13C NMR (150 MHz, CDCl3,
298.0 K) d (ppm): 165.38 (C@O), 151.54 (Ar–C), 147.32 (Ar–C),
136.07 (Ar–CH), 134.87 (Ar–CH), 129.25 (Ar–CH), 129.07
(Ar–CH), 129.03 (Ar–CH), 128.78 (Ar–CH), 128.01 (Ar–CH),
125.25 (Ar–CH), 124.67 (Ar–CH), 123.27 (Ar–CH), 119.21
(KBr)
v
(cmꢁ1): 3364, 2978, 2934, 1691, 1526, 1278, 781;
APCI-MS: m/z (M+1)+ = 505.
2.4.8. Synthesis of N-(aminoethyl)-2,3-bis(benzyloxy)benzamide, TFA
salt (5a)
A mixture of TFA (trifluoroacetic acid)/CH2Cl2 (20 vol%, 15 mL)
was dropped into a solution of N-(N-tert-butyloxycarbonylethane
diamino)-2,3-bis(benzyloxy)benzamide 4a (0.95 g, 2.0 mmol) in
CH2Cl2 (15 mL) at 0 °C, and the obtained solution was stirred at
room temperature for 3 h. Then, the solution was concentrated in
vacuo, and the residue was dissolved in 0.5 mL of hot ethanol with
30 mL ether added and the white crystal was precipitated. Then
the solution was filtered to give 5a as white solid (0.75 g, 77%).
1H NMR (300 MHz, CDCl3, 298.0 K) d (ppm): 8.42 (br s, 1H,
CO–NH), 7.56 (m, 1H, Ar–H), 7.50–7.00 (m, 12H, Ar–H), 5.14 (s,
2H, O–CH2–Ar), 5.11 (s, 2H, O–CH2–Ar), 3.33 (q, J 4.8 Hz, 2H,
CH2), 2.93 (t, J 4.8 Hz, 2H, CH2); 13C NMR (150 MHz, CD3OD,
298.0 K) d (ppm): 168.26 (C@O), 152.03 (Ar–C), 146.20 (Ar–C),
136.72 (Ar–CH), 128.66 (Ar–CH), 128.26 (Ar–CH), 128.22
(Ar–CH), 128.18 (Ar–CH), 127.95 (Ar–CH), 127.88 (Ar–CH),
127.62 (Ar–CH), 124.17 (Ar–CH), 121.46 (Ar–CH), 117.20
(Ar–CH), 75.94 (CH2), 70.86 (CH2), 39.37 (CH2), 37.19 (CH2); FTIR
(Ar–CH), 77.35 (CH2), 71.77 (CH2); FTIR (KBr)
v
(cmꢁ1): 3063,
3032, 2944, 2876, 1692, 1598, 1577, 1498, 1472, 1260, 1035,
766; APCI-MS: m/z (Mꢁ1)ꢁ = 333.
2.4.5. Synthesis of N-(N’-tert-butyloxycarbonylethane diamino)-2,3-
bis(benzyloxy)benzamide (4a)
A
mixture of 2,3-bis(benzyloxy)benzoic acid
2
(2.18 g,
6.5 mmol), N–hydroxybenzotriazole (HOBt, 0.14 g, 1.0 mmol) and
dicyclohexylcarbodiimide (DCC, 1.62 g, 7.8 mmol) was dissolved
in 80 mL CH2Cl2 and stirred for 30 min. Then 1.04 g (2-aminobutyl)
carbamic acid tert-butyl ester 2a (6.5 mmol) was added dropwise
and the reaction proceeded at room temperature overnight. The
obtained white solution was filtered to remove the dicyclohexy-
lurea, and the filtrate was concentrated in vacuo. The residue
was chromatographed on a silica gel column (ethanol:CH2Cl2,
1:10) to give 4a as yellow solid (2.72 g, 88%). Rf = 0.4. 1H NMR
(600 MHz, CDCl3, 298.0 K) d (ppm): 7.99 (br s, 1H, CO–NH), 7.64
(m, 1H, Ar–H), 7.46–7.00 (m, 12H, Ar–H), 5.09 (s, 2H, O–CH2–Ar),
5.02 (s, 2H, O–CH2–Ar), 3.29 (m, 2H, CH2), 3.09 (m, 2H, CH2), 1.33
(s, 9H, CH3); 13C NMR (150 MHz, CDCl3, 298.0 K) d (ppm): 166.17
(C@O), 156.22 (C@O), 153.15 (Ar–C), 151.91 (Ar–CH), 147.00
(Ar–C), 136.57 (Ar–CH), 129.06 (Ar–CH), 129.02 (Ar–CH), 128.98
(Ar–CH), 128.90 (Ar–CH), 128.49 (Ar–CH), 127.88 (Ar–CH),
124.62 (Ar–CH), 123.43 (Ar–CH), 117.36 (Ar–CH), 79.43 (CH2),
76.68 (CH2), 71.17 (CH2), 41.10 (CH2), 39.80 (CH2), 28.57 (CH3);
(KBr)
v
(cmꢁ1): 3379, 3064, 1688, 1576, 1453, 1273, 1200, 1056,
755, 741; APCI-MS: m/z (M+1)+ = 491.
2.4.9. Synthesis of N-(3-aminopropyl)-2,3-bis(benzyloxy)benzamide,
TFA salt (5b)
Using the same procedure as 5a, 5b was obtained as white solid
(76%). 1H NMR (600 MHz, CD3OD, 298.0 K) d (ppm): 7.90 (br s, 1H,
CO–NH), 7.49 (m, 1H, Ar–H), 7.45–7.10 (m, 12H, Ar–H), 5.19 (s, 2H,
O–CH2–Ar), 5.12 (s, 2H, O–CH2–Ar), 3.33 (m, 2H, CH2), 2.84 (t, J
7.2 Hz, 2H, CH2), 1.78 (m, 2H, CH2); 13C NMR (150 MHz, CD3OD,
298.0 K) d (ppm): 168.11 (C@O), 151.99 (Ar–C), 146.13 (Ar–C),

390
S. Lei et al. / Polyhedron 119 (2016) 387–395
136.83 (Ar–CH), 128.53 (Ar–CH), 128.36 (Ar–CH), 128.26 (Ar–CH),
128.18 (Ar–CH), 128.15 (Ar–CH), 127.87 (Ar–CH), 127.62 (Ar–CH),
124.13 (Ar–CH), 121.19 (Ar–CH), 116.91 (Ar–CH), 75.77 (CH2),
2.4.13. Synthesis of N,N’-bis(N’’-(aminopropyl)-2,3-bis(benzyloxy)
benzamide)malonamide (7b)
Using the same procedure as 7a. Purification on silica gel (etha-
nol:CH2Cl2, 1:20) afforded 7b as clear oil (83%). Rf = 0.5. 1H NMR
(600 MHz, CDCl3, 298.0 K) d (ppm): 8.02 (t, J 6.0 Hz, 2H, CO–NH),
7.67 (m, 2H, Ar–H), 7.70–7.20 (m, 22H, Ar–H), 7.13 (m, 2H, Ar–H),
5.15 (s, 4H, O–CH2–Ar), 5.09 (s, 4H, O–CH2–Ar), 3.28 (m, 4H, CH2),
3.26–3.10 (m, 6H, CH2 and CO–CH2–CO), 1.49 (t, J 6.3 Hz, 2H, CH2);
13C NMR (150 MHz, CDCl3, 298.0 K) d (ppm): 167.58 (C@O), 166.06
(C@O), 151.91 (Ar–C), 147.06 (Ar–C), 136.63 (Ar–CH), 128.98
(Ar–CH), 128.95 (Ar–CH), 128.93 (Ar–CH), 128.89 (Ar–CH), 128.46
(Ar–CH), 127.85 (Ar–CH), 128.47 (Ar–CH), 127.85 (Ar–CH),
127.24 (Ar–CH), 126.61 (Ar–CH), 124.64 (Ar–CH), 123.22 (Ar–CH),
117.38 (Ar–C), 76.71 (CH2), 71.58 (CH2), 43.25 (CH2), 36.83 (CH2),
70.83 (CH2), 36.74 (CH2), 35.74 (CH2), 27.32 (CH2); FTIR (KBr)
v
(cmꢁ1): 3345, 3064, 3032, 2971, 2929, 2852, 1712, 1679, 1665,
1576, 1528, 1454, 1261, 755; APCI-MS: m/z (M+1)+ = 505.
2.4.10. Synthesis of N-(4-aminobutyl)-2,3-bis(benzyloxy)benzamide,
TFA salt (5c)
Using the same procedure as 5a, 5b was obtained as white solid
(78%). 1H NMR (600 MHz, CD3OD, 298.0 K) d (ppm): 8.36 (br s, 1H,
CO–NH), 7.48 (m, 1H, Ar–H), 7.45–7.10 (m, 12H, Ar–H), 5.16 (s, 2H,
O–CH2–Ar), 5.09 (s, 2H, O–CH2–Ar), 3.30 (m, 2H, CH2), 2.84 (t, J
7.5 Hz, 2H, CH2), 1.59 (m, 2H, CH2), 1.47 (m, 2H, CH2); 13C NMR
36.64 (CH2), 29.56 (CH2); FTIR (KBr)
v
(cmꢁ1): 3368, 2980, 2936,
1686, 1530, 1479, 779; APCI-MS: m/z (M+1)+ = 849.
(150 MHz, CD3OD, 298.0 K)
d (ppm): 168.78 (C@O), 153.52
(Ar–C), 147.82 (Ar–C), 138.43 (Ar–CH), 138.26 (Ar–CH), 130.15
(Ar–CH), 129.89 (Ar–CH), 129.74 (Ar–CH), 129.68 (Ar–CH),
129.61 (Ar–CH), 129.34 (Ar–CH), 129.08 (Ar–CH), 125.63
(Ar–CH), 122.88 (Ar–CH), 118.52 (Ar–CH), 77.36 (CH2), 72.53
(CH2), 40.46 (CH2), 39.93 (CH2), 27.41 (CH2), 26.01 (CH2), 25.62
2.4.14. Synthesis of N,N’-bis(N’’-(aminobutyl)-2,3-bis(benzyloxy)
benzamide)malonamide (7c)
Using the same procedure as 7a. Purification on silica gel (etha-
nol:CH2Cl2, 1:20) afforded 7c as clear oil (81%). Rf = 0.5. 1H NMR
(600 MHz, CDCl3, 298.0 K) d (ppm): 7.89 (t, J 5.4 Hz, 2H, CO–NH),
7.61 (m, 2H, Ar–H), 7.40–7.10 (m, 22H, Ar–H), 7.04 (m, 2H, Ar–H),
5.05 (s, 4H, O–CH2–Ar), 4.99 (s, 4H, O–CH2–Ar), 3.16 (m, 4H, CH2),
3.10–3.00 (m, 6H, CH2 and CO–CH2–CO), 1.40–1.20 (m, 8H, CH2);
13C NMR (150 MHz, CDCl3, 298.0 K) d (ppm): 167.57 (C@O),
165.44 (C@O), 151.89 (Ar–C), 147.00 (Ar–C), 136.63 (Ar–CH),
136.61 (Ar–CH), 128.92 (Ar–CH), 128.90 (Ar–CH), 128.87 (Ar–CH),
128.45 (Ar–CH), 127.85 (Ar–CH), 127.24 (Ar–CH), 126.61 (Ar–CH),
124.64 (Ar–CH), 123.22 (Ar–CH), 117.24 (Ar–C), 76.70 (CH2), 71.52
(CH2), 42.82 (CH2), 39.40 (CH2), 39.28 (CH2), 27.17 (CH2), 26.61
(CH2); FTIR (KBr)
v
(cmꢁ1): 3367, 3033, 2951, 2882, 1728, 1649,
1577, 1454, 1203, 757; APCI-MS: m/z (M+1)+ = 519.
2.4.11. Synthesis of N-(2-(2-aminoethoxy)ethanol)-2,3-bis(benzyloxy)
benzamide (6d)
Using the same procedure as 4a. Purification on silica gel (ace-
tone:hexane, 2:3) afforded 6d as yellow solid (90%). Rf = 0.4. 1H
NMR (600 MHz, CDCl3, 298.0 K) d (ppm): 8.01 (br s, 1H, CO–NH),
7.74 (m, 1H, Ar–H), 7.50–7.10 (m, 12H, Ar–H), 5.15 (s, 2H,
O–CH2–Ar), 5.08 (s, 2H, O–CH2–Ar), 3.60–3.40 (m, 8H, CH2); 13C
NMR (150 MHz, CDCl3, 298.0 K) d (ppm): 165.50 (C@O), 151.93
(Ar–C), 146.85 (Ar–C), 136.55 (Ar–C), 128.98 (Ar–CH), 128.81
(Ar–CH), 128.72 (Ar–CH), 128.41 (Ar–CH), 127.85 (Ar–CH),
117.12 (Ar–CH), 76.39 (CH2), 72.25 (CH2), 71.41 (CH2), 69.75
(CH2); FTIR (KBr)
v
(cmꢁ1): 3378, 3065, 3032, 2930, 2870, 1650,
1575, 1535, 1498, 1454, 755, 698; APCI-MS: m/z (M+1)+ = 877.
2.4.15. Synthesis of bis(2,3-bis(benzyloxy)-N-(2-(2-aminoethoxy)
ethanol)benzamide)malonate (7d)
(CH2), 61.78 (CH2), 39.57 (CH2); FTIR (KBr)
v
(cmꢁ1): 3369, 3062,
A mixture of malonyl dichloride (0.28 g, 2 mmol) and Et3N
(0.2 g, 2 mmol) was dissolved in 20 mL CH2Cl2 and then dropped
to a solution of 6d (1.68 g, 4 mmol) in 20 mL CH2Cl2 under ice bath
and vigorous stirring conditions. The stirring was maintained at
room temperature for 5 h. Purification on silica gel (toluene:ethyl
acetate, 1:1) afforded 7d as clear oil (82%). Rf = 0.6. 1H NMR
(400 MHz, CDCl3, 298.0 K) d (ppm): 8.21 (br s, 2H, CO–NH), 7.69
(m, 2H, Ar–H), 7.50–7.10 (m, 24H, Ar–H), 5.13 (s, 4H, O–CH2–Ar),
5.05 (s, 4H, O–CH2–Ar), 4.07 (t, J 4.8 Hz, 4H, CH2), 3.55–3.40 (m,
12H, CH2), 3.29 (s, 2H, CH2); 13C NMR (150 MHz, CDCl3, 298.0 K)
d (ppm): 166.54 (C@O), 165.50 (C@O), 151.94 (Ar–C), 146.78
(Ar–C), 136.52 (Ar–CH), 129.01 (Ar–CH), 128.82 (Ar–CH), 128.73
(Ar–CH), 128.67 (Ar–CH), 127.85 (Ar–CH), 117.02 (Ar–C), 76.32
(CH2), 71.34 (CH2), 69.61 (CH2), 68.54 (CH2), 64.48 (CH2), 41.18
3036, 2936, 2878, 2852, 1658, 1627, 1576, 1454, 1271, 757, 741;
APCI-MS: m/z (M+1)+ = 422.
2.4.12. Synthesis of N,N’-bis(N’’-(aminoethyl)-2,3-bis(benzyloxy)
benzamido)malonamide (7a)
N-(aminoethyl)-2,3-bis(benzyloxy)-benzamide, TFA salt 5a
(1.96 g, 4 mmol) in 20 mL 1.25 M NaOH aqueous solution was stir-
red 20 min. CH2Cl2 extraction (20 mL ꢂ 3), the organic layer was
dried over anhydrous Na2SO4, filtered, and evaporated to dryness
to give N-(aminoethyl)-2,3-bis(benzyloxy)benzamide 6a as clear
oil (1.3 g, 87%). A mixture of malonyl dichloride (0.28 g, 2 mmol)
and Et3N (0.2 g, 2 mmol) was dissolved in 20 mL CH2Cl2 and then
dropped to a solution of 6a in 20 mL CH2Cl2 under ice bath and vig-
orous stirring conditions. The stirring was maintained at room
temperature for 5 h. Purification on silica gel (ethanol:CH2Cl2,
1:20) afforded 7a as clear oil (1.34 g, 82%). Rf = 0.5. 1H NMR
(600 MHz, CDCl3, 298.0 K) d (ppm): 8.12 (t, J 8.7 Hz, 2H, CO–NH),
7.65 (m, 2H, Ar–H), 7.50–7.23 (m, 22H, Ar–H), 7.13 (m, 2H,
Ar–H), 5.14 (s, 4H, O–CH2–Ar), 5.08 (s, 4H, O–CH2–Ar), 3.34 (m,
4H, CH2), 3.22 (m, 4H, CH2), 2.97 (s, 2H, CO–CH2–CO); 13C NMR
(150 MHz, CDCl3, 298.0 K) d (ppm): 167.87 (C@O), 166.54 (C@O),
151.90 (Ar–C), 146.93 (Ar–C), 136.53 (Ar–CH), 129.89 (Ar–CH),
129.02 (Ar–CH), 128.98 (Ar–CH), 128.94 (Ar–CH), 128.88
(Ar–CH), 128.78 (Ar–CH), 128.47 (Ar–CH), 127.85 (Ar–CH),
127.24 (Ar–CH), 126.61 (Ar–CH), 124.64 (Ar–CH), 123.22
(Ar–CH), 117.37 (Ar–C), 76.63 (CH2), 71.46 (CH2), 42.99 (CH2),
(CH2), 39.60 (CH2); FTIR (KBr)
v
(cmꢁ1): 3399, 3366, 3063, 3032,
2933, 2872, 1758, 1732, 1657, 1576, 1533, 1454, 757, 698;
APCI-MS: m/z (M+1)+ = 911.
2.4.16. Synthesis of N,N’-bis(N’’-(aminoethyl)-2,3-bis(hydroxy)
benzamide)malonamide (8a)
A mixture of 7a (0.82 g, 1 mmol) and 10% Pd/C (200 mg) was
dissolved in 50 mL THF (tetrahydrofuran) and stirred under H2
(130 mL/min) atmosphere for 5 h. The resulting mixture was fil-
tered over Celite, and the filtrate was concentrated in vacuo to give
8a as clear oil (0.45 g, 99%). 1H NMR (600 MHz, (CD3)2CO, 298.0 K)
d (ppm): 13.01 (br s, 2H, Ar–OH), 8.40 (s, 2H, CO–NH), 7.96 (s, 2H,
CO–NH), 7.72 (br s, 2H, Ar–OH), 7.24 (dd, J 7.8 and 1.2 Hz, 2H,
Ar–H), 6.96 (dd, J 7.8 and 1.2 Hz, 2H, Ar–H), 6.71 (t, J 7.8 Hz, 2H,
Ar–H), 3.53 (m, 4H, CH2), 3.47 (m, 4H, CH2), 3.21 (s, 2H,
CO–CH2–CO); 13C NMR (150 MHz, (CD3)2CO, 298.0 K) d (ppm):
40.18 (CH2), 39.19 (CH2); FTIR (KBr)
v
(cmꢁ1): 3296, 3065, 3032,
2934, 1666, 1637, 1576, 1533, 1497, 1450, 753, 731; APCI-MS:
m/z (M+1)+ = 821.

S. Lei et al. / Polyhedron 119 (2016) 387–395
391
(Boc)2O,
Et3N,MeOH
H2N
H2N
NH2
NH Boc
70-75%
O
NH
OBn
NH Boc
1a-c
2a-c
DCC,HOBt,
DCM
86-90%
O
OH
O
OH
OBn
1) acetone,
BnBr,K2CO3
OH
OBn
OBn
4a-c
2) MeOH,
LiOH,HCl
OH
3
+ CF3COO-
NH2
O
NH
O
NH
NH3
OBn
OBn
OBn
OBn
NaOH
DCM,TFA
76-78%
6a-c
5a-c
Scheme 3. Synthetic routes for benzamides 6a–6c.
(s, 2H, CO–NH), 7.68 (s, 2H, CO–NH), 7.28 (dd, J 8.4 and 1.2 Hz,
2H, Ar–H), 6.96 (dd, J 7.8 and 1.2 Hz, 2H, Ar–H), 6.70 (t, J 8.4 Hz,
2H, Ar–H), 3.44 (m, 4H, CH2), 3.26 (m, 4H, CH2), 3.12 (s, 2H,
CO–CH2–CO), 1.65 (m, 4H, CH2), 1.57 (m, 4H, CH2); 13C NMR
(150 MHz, (CD3)2CO, 298.0 K) d (ppm): 171.14 (C = O), 168.09
(C = O), 150.61 (Ar–C), 147.16 (Ar–C), 119.11 (Ar–CH), 118.99
(Ar–CH), 117.61 (Ar–CH), 115.49 (Ar–C), 39.64 (CH2), 39.36 (CH2),
O
OH
OBn
NH
OBn
OH
O
DCC,HOBt,
DCM,1d
OBn
OBn
6d
(90%)
3
30.70 (CH2), 27.66 (CH2), 27.25 (CH2); FTIR (KBr)
v
(cmꢁ1): 3366,
Scheme 4. Synthesis of benzamide 6d.
2933, 2870, 1641, 1589, 1546, 1486, 1459, 742; APCI-MS: m/z
(M+1)+ = 517.
171.60 (C@O), 150.93 (Ar–C), 147.29 (Ar–C), 119.26 (Ar–CH),
119.02 (Ar–CH), 117.74 (Ar–CH), 115.36 (Ar–C), 40.50 (CH2),
39.63 (CH2), 30.71 (CH2); FTIR (KBr)
v
(cmꢁ1): 3323, 2945, 1644,
2.4.19. Synthesis of bis(2,3-bis(hydroxy)-N-(2-(2-aminoethoxy)
ethanol)benzamide)malonate (8d)
1589, 1545, 1489, 1459, 741; APCI-MS: m/z (M+1)+ = 461.
Using the same procedure as 8a, 8d was obtained as clear oil
(99%). 1H NMR (600 MHz, (CD3)2CO, 298.0 K) d (ppm): 8.02 (s,
2H, CO–NH), 7.13 (dd, J 7.8 and 1.8 Hz, 2H, Ar–H), 6.83 (dd, J 7.8
and 1.8 Hz, 2H, Ar–H), 6.58 (t, J 7.8 Hz, 2H, Ar–H), 4.10 (m, 4H,
CH2), 3.60–3.40 (m, 12H, CH2), 3.28 (s, 2H, CH2); 13C NMR
(150 MHz, (CD3)2CO, 298.0 K) d (ppm): 170.46 (C@O), 166.45
(C@O), 149.81 (Ar–C), 146.34 (Ar–C), 118.46 (Ar–CH), 118.24
(Ar–CH), 116.83 (Ar–CH), 114.57 (Ar–C), 68.93 (CH2), 68.34 (CH2),
2.4.17. Synthesis of N,N’-bis(N’’-(3-aminopropyl)-2,3-bis(hydroxy)
benzamide)malonamide (8b)
Using the same procedure as 8a, 8b was obtained as clear oil
(99%). 1H NMR (600 MHz, (CD3)2CO, 298.0 K) d (ppm): 8.39 (s,
2H, CO–NH), 7.82 (s, 2H, CO–NH), 7.26 (dd, J 7.8 and 1.2 Hz, 2H,
Ar–H), 6.96 (dd, J 7.8 and 1.2 Hz, 2H, Ar–H), 6.71 (t, J 8.4 Hz, 2H,
Ar–H), 3.47(m, 4H, CH2), 3.37 (m, 4H, CH2), 3.26 (s, 2H, CO–CH2–
CO), 1.78 (m, 4H, CH2); 13C NMR (150 MHz, (CD3)2CO, 298.0 K) d
(ppm): 171.04 (C@O), 168.90 (C@O), 150.62 (Ar–C), 147.18
(Ar–C), 119.14 (Ar–CH), 119.09 (Ar–CH), 117.52 (Ar–CH), 115.49
(Ar–C), 36.99 (CH2), 36.73 (CH2), 34.99 (CH2), 30.71 (CH2); FTIR
64.21 (CH2), 39.19 (CH2), 39.07 (CH2); FTIR (KBr)
v
(cmꢁ1): 3390,
2956, 1747, 1641, 1487, 1459; APCI-MS: m/z (M+1)+ = 551.
3. Results and discussion
(KBr)
v
(cmꢁ1): 3328, 2934, 1642, 1589, 1546, 1488, 1459, 787,
741; APCI-MS: m/z (M+1)+ = 489.
3.1. Synthesis and characterization of ligands 8a–8d
2.4.18. Synthesis of N,N’-bis(N’’-(4-aminobutyl)-2,3-bis(hydroxy)
benzamide)malonamide (8c)
In this work, the first step in ligand synthesis was protecting
2,3-dihydroxybenzoic acid. Diamines 1a–1c reacted directly with
2,3-bis(benzyloxy)benzoic acid 3 to yield the main products
N,N0-bis(2,3-bis(benzyloxy)benzamide) diamides rather than our
Using the same procedure as 8a, 8c was obtained as clear oil
(99%). 1H NMR (600 MHz, (CD3)2CO, 298.0 K)
d (ppm): 8.23
O
O
XH
O
NH
OBn
O
NH
OR
HN
RO
O
X
X
malonyl dichloride
OBn
OR
RO
DCM,Et3N
81-83%
6a-d
7a-d
: R = Bn
Pd/C,H2,
THF 99%
a-c
d
: X = NH
: X = O
8a-d: R = H
Scheme 5. General synthetic routes of biscatecholamide ligands 8a–8d.

392
S. Lei et al. / Polyhedron 119 (2016) 387–395
Table 1
Protonation constants (logKiH) of the tetradentate ligands 8a–8d and catechol for comparison.
logKiH
8a
8b
8c
8d
Catecholb
logKH1 a
logKH2
logKH3
logKH4
11.80(2)
10.66(3)
8.49(1)
7.41(2)
11.70(1)
10.73(1)
8.08(3)
7.11(2)
11.47(2)
10.65(1)
8.36(2)
7.18(2)
12.37(3)
10.11(3)
7.36(1)
7.14(2)
13.0
9.24
–
–
a
I = 0.1 M KCl, 25.0 0.1 °C. KiH = [HiL]/([Hi-1L] [H]).
Ref. [34].
b
Fig. 1. Concentration distribution curves calculated for the free ligands in aqueous solution: ligands 8a (A), 8b (B), 8c (C) and 8d (D). CL = 2.0 ꢂ 10ꢁ4 M.
Table 2
Global formation constants (logbpqr) for complexes of ligands 8a–8d with UO22+; pM values for these compounds and some relevant synthetic ligands at pH = 7.4.a
(p, q, r)
logbpqr
8a
8b
8c
8d
9b
10c
(1, ꢁ1, 1)
(1, 0, 1)
(1, 1, 1)
(1, 2, 1)
pUO2
21.54(3)
27.76(2)
32.66(2)
35.68(3)
20.85
20.11(1)
29.07(2)
35.06(2)
37.87(3)
21.51
20.83(2)
26.74(2)
31.90(3)
34.55(3)
20.68
22.02(3)
28.83(2)
34.04(2)
37.02(4)
22.41
6.97
13.9
–
–
21.95
26.86
30.79
19.2
–
15.39
a
b
c
I = 0.1 M KCl, 25.0 0.1 °C. pM = ꢁlog[M] with CL/CM = 10 and CM = 10ꢁ6 M. bpqr = [MpHqLr]/([M]p[H]q[L]r).
Ref. [44].
Ref. [45].
target molecules because of the same activity of the two terminal
amines [7]. Thus, mono-protecting diamines 1a–1c are necessary.
The synthesis of 6a–6c is shown in Scheme 3. First, mono-Boc pro-
tections of diamines 2a–2c from commercially available diamines
1a–1c were obtained. Then, N-Boc-diamines 2a–2c were added
into the mixture of 2,3-bis(benzyloxy)benzoic acid 3 and DCC/
HOBt to yield the desired benzamides 4a–4c in 86–90% yields. Ben-
zamides 5a–5c were generated using 20% trifluoroacetic acid/CH2-
Cl2 in an ice bath, and then 1.25 M NaOH aqueous solution was
used to obtain the desired amides 6a–6c.

S. Lei et al. / Polyhedron 119 (2016) 387–395
393
R
The NMR, FTIR and mass spectra data of ligands 8a–8d are listed
in Experimental section. The UV–Vis spectra of ligands 8a–8d were
recorded in aqueous solution. All absorption bands of ligands
O
OH
H
N
HN
NH
O
O
O
O
O
O
N
H
OH
O
HO
O
n ? p⁄ transitions range within 319–322 nm, and those of
p ?
p⁄
OH
OH
N
transitions range within 208–214 nm and 246–249 nm,
respectively.
N
N
N
H
N
N
H
R =
O
O
OH
3
N
3.2. Complexation studies
3
H
O
10
9
The complexation behavior of biscatecholamide ligands 8a–8d
was studied as follows. The measurements were carried out
beyond the pH 3–11 range of the experiments, and the fitting anal-
yses of the corresponding spectrophotometric titration curve by
the HypSpec 2014 program and potentiometric titration curve by
the Hyperquad 2013 program yielded the global protonation con-
stants (logb). These constants were used to calculate the stepwise
protonation constants (logKiH) presented in Table 1. The protona-
tion constant for the previously reported catechol is also listed in
this table for comparison. In neutral form, ligands 8a–8d have four
dissociable protons. The first two protonation constants are easily
assigned to the meta hydroxyl groups, whereas the last two proto-
nation constants are assigned to the ortho hydroxyl groups. Both
the average logKiH values of the first two protonation constants
and the last two protonation constants are lower than the two
values of catechol. This result indicates that the obtained ligands
8a–8d have slightly more acidic protonation constants than
catechol. This acidifying effect can be explained by the electron-
withdrawing effect of the amide carbonyl groups [43].
Scheme 6. Molecular structure of ligands 9 and 10.
Another route was used to obtain 6d (Scheme 4) because amino
has a greater nucleophilicity than hydroxyl. The addition of
2-(2-aminoethoxy)ethanol 1d on 2,3-bis (benzyloxy) benzoic acid
3 in the presence of HOBt/DCC produced N-(2-(2-aminoethoxy)
ethanol)-2,3-bis (benzyloxy)benzamide 6d in good yield.
The synthesis of 8a–8d is reported in Scheme 5. The addition of
malonyl dichloride to benzamides 6a–6d assisted by Et3N as the
deacid reagent produced the biscatecholamide analogs 7a–7d in
81–83% yield. Deprotection of the hydroxyl groups under typical
benzyl group-removal catalytic hydrogenation conditions (room
temperature, 130 mL/min H2, atmospheric pressure, and Pd/C in
THF produced 8a–8d in 99% yield.
The structures of biscatecholamide ligands 8a–8d were fully
confirmed by their 1H NMR, 13C NMR, FTIR spectroscopy, UV–Vis
spectrophotometry and mass spectrometry. Resonance signals of
the catechol protons of symmetric biscatecholamides 8a–8d were
recorded in (CD3)2CO solution using TMS as internal standard.
The concentration distribution of ligands 8a–8c can be accom-
plished on the basis of the calculated protonation constants with
Fig. 2. Concentration distribution curves of the complexes formed in the system UO22+-ligands 8a–8d at a 1:1 metal-to-ligand ratio: UO22+-ligands 8a (A), 8b (B), 8c (C) and 8d
(D). CL = CM = 1.852 ꢂ 10ꢁ4 M.

394
S. Lei et al. / Polyhedron 119 (2016) 387–395
Scheme 7. Proposed speciation in uranyl titrations with chelating agents 8a–8d (Uranyl oxo atoms are omitted).
Table 3
Global formation constants (logbpqr) for complexes of ligands 8a–8d with Cu2+ and Zn2+; pM values for these compounds at pH = 7.4.a
(p, q, r)
logbpqr
8a
8b
8c
8d
[CupHqLr]
[ZnpHqLr]
(1, 0, 1)
(1, 1, 1)
(1, 3, 1)
(1, 4, 1)
pCu
23.94(1)
29.40(2)
39.69(2)
44.20(2)
15.82
24.02(3)
29.45(2)
39.86(1)
43.65(1)
16.43
23.30(1)
28.65(3)
39.28(2)
43.28(1)
15.74
24.82(5)
30.04(3)
40.23(2)
44.07(3)
17.71
(1, 0, 1)
(1, 1, 1)
(1, 3, 1)
pZn
15.48(2)
22.29(3)
35.57(1)
7.48
14.37(1)
21.16(1)
34.65(2)
6.94
14.35(2)
21.21(2)
34.65(3)
6.96
13.97(3)
20.83(3)
34.14(2)
7.02
a
I = 0.1 M KCl, 25.0 0.1 °C. pM = ꢁlog[M] with CL/CM = 10 and CM = 10ꢁ6 M. bpqr = [MpHqLr]/([M]p[H]q[L]r).
of ligands 8a–8d and reported tetradentate ligands 9 [42] and 10
[43] (Table 2 and Scheme 6). In general, a higher pM represents a
lower concentration of uncomplexed metal ion in solution, which
indicates that the corresponding metal ion and ligand exhibit a
strong complexation ability. The pM values are calculated at stan-
dard conditions of [M] = 10ꢁ6 M and [L] = 10ꢁ5 M, and the mini-
mum pM value is 6.0 while no metal complexing. As shown in
Table 2, the pUO2 values of ligands 8a–8d are significantly higher
than those of 9 and 10 at the physiological pH, which may be
attributed to their low protonation constants. And it also reveals
that the uranyl affinity is closely related to the structure of
chelators.
The corresponding concentration distribution curves of the
complexes formed in the system UO22+-ligands 8a–8d were plotted
using the Hyss program with the global protonation constants
(logb) and global formation constants (logbpqr), as shown in
Fig. 2. Upon deprotonation and uranyl coordination to form a [UO2-
H2L] complexes at a low pH, amide carbonyl groups of ligands 8a–
8d gain a intramolecular hydrogen-bonding interaction with the
ortho oxygen protons and the UO22+ ion bonding two ortho oxygen
donors while two meta hydroxyl groups remained. At pH 3–4, the
[UO2HL]ꢁ complexes display a rapid increase in the total metal
concentration, indicating the formation of complexes with the
simultaneous deprotonation of these ligands. Following generating
[UO2L(H2O)]2ꢁ complexes, stepwise deprotonation was unreason-
able. A partial hydrolysis of the uranyl center occurs upon increas-
Fig. 3. Antioxidant results of 8a–8d aqueous solutions determined by scavenging
DPPH radical at 517 nm.
the Hyss program. As shown in Fig. 1, the major species of ligands
8a–8c is H3L about 60% at the physiological pH. However, H3L of
ligand 8d at this pH is just 40%, which can be attributed to the dif-
ferent backbone.
The uranyl affinities of ligands 8a–8d were determined by per-
forming spectrophotometric titrations under experimental condi-
tions. UO22+ has two axial oxygen atoms and equatorial 4–6 sites,
and commonly forms 1:1 species with tetradentate ligands
[44,45]. Uranyl titrations were monitored using a 1:1 metal-to-
ligand ratio and titration data were calculated using the HypSpec
2014 program with hydrolysis constants of UO22+ [46], and the
coordination stability constants of ligands 8a–8d with UO22+ at
the physiological pH are listed in Table 2. Global formation con-
stants (logbpqr) for complexes are species dependent, so it is diffi-
cult to compare the uranyl affinities. Thus, a species independent
pM value is used. Studies of tetradentate catechol ligands with
UO22+ by using spectrophotometric titrations are rare in the litera-
ture. Table 2 listed the global formation constants and pUO2 values
ing pH, resulting in
a
[UO2L(OH)]3ꢁ species, which can be
attributed to the switching of hydroxy and solvent in solution at
the fifth equatorial coordination position on uranyl [44,45], and
the proposed speciation is shown in Scheme 7.
The stability constants of ligands 8a–8d with Cu2+ and Zn2+
were also investigated under the same experimental conditions,
and the distribution curves are shown in Supporting Information
(Figs. S13 and S14). The hydrolysis constants of Cu2+ and Zn2+ have
also been taken into account according to the literature [47,48].
The global formation constants logbpqr and the pM (M = Cu2+ and
Zn2+) values for the complex of ligands 8a–8d are listed in Table 3.
The complexes for ligands 8a–8d are four species with Cu2+
,

S. Lei et al. / Polyhedron 119 (2016) 387–395
395
[CuL]2ꢁ, [CuHL]ꢁ, [CuH3L]+ and [CuH4L]2+, as well as three species
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Acknowledgments
We are grateful for financial support from the National Natural
Science Foundation of China (Project No. 21301142, 51572230),
Applied Basic Research Program of Sichuan Province (Project No.
2014JY0170), Open Project of State Key Laboratory Cultivation Base
for Nonmetal Composites and Functional (Project No. 14zdfk05),
and Southwest University of Science and Technology Outstanding
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Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.poly.2016.09.006.