Lanthanide complexes with N-(2,6-dimethylphenyl)oxamate: Synthesis, characterisation and cytotoxicity

Article abstract of DOI:10.1016/j.poly.2020.114561

The complexation reactions of Ce(III), Nd(III), Gd(III) and Er(III) ions with the chelating/ bridging monoanionic ligand N-(2,6-dimethylphenyl)oxamate (Hpma^?) in basic media were performed in view of the potential applications of oxamate deriva

Full text of DOI:10.1016/j.poly.2020.114561

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Lanthanide complexes with N-(2,6-dimethylphenyl)oxamate: Synthesis, char‐
acterisation and cytotoxicity
Tatenda Madanhire, Hajierah Davids, Melanie C. Pereira, Eric C. Hosten,
Abubak'r Abrahams
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https://doi.org/10.1016/j.poly.2020.114561
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28 March 2020
Please cite this article as: T. Madanhire, H. Davids, M.C. Pereira, E.C. Hosten, A. Abrahams, Lanthanide
complexes with N-(2,6-dimethylphenyl)oxamate: Synthesis, characterisation and cytotoxicity, Polyhedron
(2020), doi: https://doi.org/10.1016/j.poly.2020.114561
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Lanthanide complexes with N-(2,6-dimethylphenyl)oxamate:
Synthesis, characterisation and cytotoxicity
Tatenda Madanhire, Hajierah Davids, Melanie C. Pereira, Eric C. Hosten and Abubak’r Abrahams*
Email: Abubakr.Abrahams@mandela.ac.za
School of Biomolecular and Chemical Sciences, PO Box 77000, Nelson Mandela University,
Port Elizabeth, 6031, South Africa
ABSTRACT
The complexation reactions of Ce(III), Nd(III), Gd(III) and Er(III) ions with the chelating/
bridging monoanionic ligand N-(2,6-dimethylphenyl)oxamate (Hpma–) in basic media were
performed in view of the potential applications of oxamate derivatives as cytotoxic agents.
The coordination compounds were characterised by different physico-chemical techniques:
elemental analysis, conductivity measurements, IR, 1H NMR and UV-Vis-NIR spectroscopy,
and X-ray crystallography. The anionic Hpma– ligand was obtained through conversion of the
proligand ethyl (2,6-dimethylphenylcarbamoyl)formate (Hdmp). The reactions afforded
lanthanide(III)–oxamate
coordination
polymers
Ce
of
the
formulae:
Nd (2)),
{[Ln(Hpma)3(MeOH)(H2O)]∙2MeOH}n
(Ln
=
(1)
and
{[Gd2(Hpma)6(MeOH)4]∙6MeOH}n (3), {[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n (4) and
[Ln2Na2(Hpma)8(EtOH)(H2O)6]n (Ln = Nd (5) and Gd (6)). The polymeric complexes feature
Ln-Hpma moieties bridged by μ2-η1:η1:η1 Hpma– ligands, giving one-dimensional zig-zag
chains of the –Ln–O–C–O–Ln– type. Atomic charge analysis and the MEP map of the Hpma–
moiety using the DFT/B3LYP method were consistent with the chelating and bridging modes
of the anionic ligand through all the oxygen atoms. An evaluation of the cytotoxic activities
of the metal salts, the proligand and the novel lanthanide complexes on MCF-7, HEC-1A and
THP-1 cells revealed that only the rare-earth metal salts [Ce(NO3)3∙6H2O] and
[Nd(NO3)3∙6H2O] showed moderate cytotoxicity against MCF-7 and HEC-1A cells,
respectively.
Keywords:
Complexes, oxamate, bidentate, bridging, heterometallic, natural charge,
cytotoxicity

1.
Introduction
The prevalence of cancer is rising each year, resulting in cancer becoming the leading cause
of death worldwide [1]. Among the most commonly diagnosed types of cancers are breast (in
women), endometrial, prostate, colorectal and lung cancer [1-4]. The metallodrug cisplatin
has been extensively used in cancer chemotherapy since the 1960s, although its clinical
applications are limited due to adverse effects, such as nausea, ototoxicity, low hydrolytic
stability and resistance in some cancer cells [5,6]. This has encouraged researchers to
investigate alternative metal complexes as potential anticancer agents with improved
effectiveness towards cancer.
Previous studies have demonstrated that complexes of the 4f elements have a relevant role in
chemotherapy, since Ln(III) compounds actively inhibit tumour growth due to the ability of
the lanthanide ion to suppress iron uptake, alter signal transduction and inhibit reactive
oxygen species production through binding to hydro-peroxides [7,8]. In addition, lanthanides
can mask free radicals by means of magnetic interactions [7]. Limitations associated with
platinum-based anticancer agents can thus potentially be overcome by resorting to
lanthanide-based drugs.
The d- and f-block metal complexes containing carboxylic acids have been widely studied
due to their potential use as anticancer agents [9]. Oxamic acid is amongst the simplest
carboxylic acid ligands examined (Figure 1), which has tumour growth inhibition properties
[9-11]. Oxamate (a structural analogue of pyruvate), or its derivatives, act by targeting
aerobic glycolysis (an abnormal process related to tumour progression and metastasis)
through the competitive inhibition of pyruvate conversion to lactate by lactate dehydrogenase
A (LDHA) [9-11]. For example, oxamate significantly inhibits the proliferation of non-small
cell lung cancer (NSCLC) cells, with the investigation revealing lower toxicity in normal
cells [12].
Complexation studies of oxamic acid and its derivatives with d- and f-block metals indicated
that these ligands have interesting ligating properties, as they chelate in a bidentate mode to
the metal ions, either via both oxygen atoms, or through one nitrogen atom and one oxygen
atom
[9,13].
For
example,
X-ray
analysis
of
the
Co(III)
complex
[Co(C2O3NH2)2(OH2)2]∙2H2O revealed coordination of oxamic acid as a bidentate O,O-donor

ligand. Other reports showed that oxamic acid can act mono-, bi-, tri- or tetradentately
(bridging) in its mono- or dianionic form [9,13]. Monodentate coordination is possible for the
monoanionic ligand using an O-atom of the carboxylic group, while tridentate binding occurs
through all the oxygen atoms. The carboxylic and amide protons are ionisable to yield a
dianionic ligand, which can act as a bridging ligand in dinuclear or polynuclear complexes
[13].
Lanthanide complexes are vital, not only in chemotherapy, but also in cancer diagnosis, due
to the versatile magnetic characteristics of the metal ion 4f electronic configuration [14]. An
example of a complex showing slow magnetic relaxation behaviour is the mononuclear
Dy(III)-oxamate complex derived from N-(2,6-dimethylphenyl)oxamic acid (H2L, Figure 1)
in a controlled basic media [15]. The isolated mononuclear Dy(III) coordination compound,
which is stabilised by metal-ligand bonds and hydrogen bonding, has the formula
Me4N[Dy(HL)4]∙2CH3CN. The oxamate ligands assume the O,O'-chelating mode, forming an
eight-coordinate environment with a distorted D2d dodecahedron geometry [15].
This paper reports on the preparation of the solid-state Ce(III), Nd(III), Gd(III) and Er(III)
complexes with N-(2,6-dimethylphenyl)oxamate (Hpma–) (Scheme 1) and their
characterisation by means of micro-analyses, infrared (IR), ultraviolet-visible-near infrared
(UV-Vis-NIR) and nuclear magnetic resonance (NMR) spectroscopy, as well as single-
crystal X-ray crystallography. We herein present Ln(III)–oxamate coordination polymers of
the formula: {[Ln(Hpma)3(MeOH)(H2O)]∙2MeOH}n (Ln = Ce (1) and Nd (2)),
{[Gd2(Hpma)6(MeOH)4]∙6MeOH}n (3), {[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n (4) and
[Ln2Na2(Hpma)8(EtOH)(H2O)6]n (Ln = Nd (5) and Gd (6)). Density Functional Theory (DFT)
calculations were performed to compare theoretical calculations and experimental findings,
and to confirm the experimental results. This work also aims at screening the anticancer
effects of the oxamate compounds by determining their in vitro cytotoxicities against breast
cancer (MCF-7), endometrial carcinoma (HEC-1A) and human monocytic (THP-1) cell lines,
using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [16,17].
The anticancer studies serve to identify compounds that may act as lead compounds in the
design of novel chemotherapeutic agents.

2.
Experimental
2.1.
General procedures
All chemicals and reagents were of analytical grade and were used without further
purification. The melting points and CHN analyses of compounds were performed on a
Stuart® Melting Point Apparatus SMP30 and an Elementar Vario EL Cube Elemental
Analyzer, respectively. A HANNA instruments (HI) 2300 EC/TDS/NaCl Meter was used for
the conductivity measurements. Nuclear Magnetic Resonance spectra were obtained at room
temperature using a Bruker AvanceIII 400 NMR spectrometer and analysis of the spectra was
performed using ACD/Labs software (version 12.0, 1997–2008). The infrared spectra were
recorded on a Bruker Tensor 27 FT-IR spectrophotometer, equipped with the platinum
attenuated total reflection (ATR) attachment. The samples were run neat on ATR and the
recorded data were analysed using the OPUS 6.5 software. Signal intensities were denoted by
the following abbreviations: w = weak, m = medium, s = strong and b = broad. The UV-Vis
spectra of the compounds were investigated using a PerkinElmer Lambda 35 UV/Vis
spectrophotometer and processing was completed using UV WinLab software (v1.0.0). Single
crystal X-ray diffraction on crystals of Hdmp and 1–6 was performed using a Bruker Kappa
Apex II X-ray Crystallography System at 296 K (Hdmp) and 200 K (1–6), using graphite
monochromated Mo Kα radiation (λ = 0.71073 Å). Molecular graphics were obtained using
ORTEPIII for Windows v2014.1 and Mercury 3.6 software [18,19]. Lanthanide geometry
analyses, through calculation of continuous shape measures (CShM values) were enabled by
the SHAPE 2.1 software, while the polyhedral views were generated using VESTA software
(version 3, 2006–2014) [20,21].
2.2.
X-ray crystallographic measurements
A summary of the crystal data, data collection and refinement parameters for the proligand
and complexes 1–6 is presented in Table 1. APEX2 (ver. 2014.11-0) was used for data
collection and the data were integrated via SAINT software (ver. 8.34A) [22]. The structures
were solved by direct methods utilising SHELXT-2018/2 and refined by least-squares
procedures using SHELXL-2018/3 with ShelXle as a graphical interface [23-25]. Empirical
absorption corrections were performed using the numerical method implemented in SADABS
[22]. All non-hydrogen atoms were refined anisotropically, while carbon-bound H-atoms

were placed in calculated positions and refined isotropically in the riding model
approximation, with Uiso(H) set to 1.2Ueq(C). The H-atoms of the methyl groups were
permitted to rotate with a fixed angle around the C—C bond to best fit the experimental
electron density (HFIX 137 in the SHELX program suite), with Uiso(H) set to 1.5Ueq(C)
[24]. The hydroxyl group H-atoms were rotated with a fixed angle around the C—O bond to
best fit the experimental electron density (HFIX 147 in the SHELX program suite), with
Uiso(H) set to 1.5Ueq(O) [24]. The nitrogen-bound H-atoms were located on a difference
Fourier map and refined freely.
2.3.
Molecular modelling
Molecular geometries of Hpma– in DMSO and the gaseous phase were optimised using
Density Functional Theory (DFT) calculations, employing the Becke3-Lee-Yang-Parr
(B3LYP) model and aug-cc-pVTZ basis set [26,27]. The calculations were performed using
the Gaussian 16 program package (Rev. B01). After optimisation, single-point energy
calculations were performed, upon which natural bond orbital (NBO) analysis was done
using the NBO 6.0 program [NBO 6.0.19 (05-Aug-2018)] [28-30]. Natural Population
Analysis (NPA) was used to determine the atomic charges of the monoanionic ligand in
solution and in the gaseous phase [31]. The surface molecular electrostatic potential (MEP)
values were computed and the electron density distribution, molecular shape and size in
three-dimensions were visualised employing MoleCoolQt64 software (2003–2012) [32]. The
Avogadro software (version 2, 1991) was used in visualising the highest occupied molecular
orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO).
2.4.
Procedures for in vitro anticancer analyses
2.4.1. Cell culture and maintenance
The MCF-7 and HEC-1A cancer cells were routinely maintained in 25 or 75 cm2 cell culture
flasks as monolayer cultures, in growth medium consisting of DMEM supplemented with
10% heat-inactivated foetal bovine serum (HI-FBS), while the THP-1 cells were regularly
maintained in RPMI-1640 medium supplemented with 10% HI-FBS. The cells were
maintained at 37 °C in a humidified atmosphere (5% CO2 and 95% air).

2.4.2. Preparation of the compounds and controls
100 mM stock solutions of the test agents were prepared in DMSO (100%) and diluted to
give final well concentrations of DMSO less than 0.1%, which did not adversely affect cell
growth. The 0.1% DMSO was used as a vehicle control. Dilutions with complete growth
medium were obtained from stock solutions, to give final well concentrations of 100 μM. A
biologically active component of the Indian Curcuma longa plant (turmeric), curcumin, was
used as a positive control [33,34]. The anticancer properties of curcumin against multiple
human carcinomas, including breast, ovarian, prostate, colon, pancreatic, and head and neck
cancers, are ascribed to its ability to target multiple pathways that effect cellular death. The
mechanisms of action of the compound include its effect in biological pathways or on various
growth factor receptors associated with cell cycle regulation, apoptosis, mutagenesis,
metastasis, oncogene expression, angiogenesis and tumorigenesis [33,34].
2.4.3. Cell counting using Trypan blue
The Trypan blue exclusion assay is an important method in cell viability determination
[35,36]. This test depends on the ability of non-viable cells (plasma membrane integrity lost)
to incorporate Trypan blue, while viable cells (intact plasma membranes) exclude the stain.
Under light microscopy, non-viable cells appear dark blue, whilst viable cells appear
colourless [35,36]. Cell counting was performed utilising a Neubauer counting chamber
(Superior). Staining of the cells was done with Trypan blue (4%) in a ratio of 1:1. The total
number of cells/mL was calculated as: the average cell count per square × dilution factor ×
104.
2.4.4. Cell viability determination using an MTT assay
The cytotoxic activity of the investigated compounds was assessed by a 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which relies on the
cellular metabolic activity of NAD(P)H-dependent oxidoreductase enzymes [16,17,37]. This
dye reduction assay is based on the reduction of the pale yellow tetrazolium salt (MTT) to
purple formazan crystals in viable cells [16,17].
The cells were seeded in 96-well tissue culture plates at a density of 104 cells/well in
complete growth medium. After an overnight incubation (37 °C), the cells were treated with

the test compounds and the controls for 24 hours, at a final well concentration of 100 μM.
Subsequently, MTT (0.5 mg/mL, 100 μL) was added to each well. For the suspension (THP-
1) cells, MTT (2.5 mg/mL) was added to the cells at 20 % v/v. The plates were then
incubated for 3 hours at 37 °C, and the purple formazan crystals that formed were solubilised
in 100 μL DMSO (100%). Absorbance values were read against a DMSO blank, at 540 nm,
using a ThermoMultiSkan Go microplate reader (Thermo Scientific, U.S.A.). Background
interference in THP-1 cell suspensions was corrected by setting up sample background
controls using equal volumes of cell culture media and MTT reagent.
The number of viable cells was extrapolated from an MTT standard curve per cell line and
the percentage cell viability was determined as a percentage of the 0.1% DMSO vehicle
control. Each experiment was completed in triplicate.
2.4.5. Statistical analysis
All data are reported as mean ± S.D. for triplicate experiments (n = 3). ANOVA was used in
the analysis of non-parametric grouping of data, whilst secondary data analysis for
significance was performed with Student's t-test. Values of p < 0.05 were regarded
significant.
2.5.
Synthesis of ethyl (2,6-dimethylphenylcarbamoyl)formate (Hdmp)
The proligand Hdmp was synthesised according to the literature procedure [38]. 2,6-
Dimethylphenylaniline (10.22 mL, 83 mmol) in 250 mL THF was treated with 9.3 mL ethyl
chlorooxoacetate (9.273 mL, 83 mmol) in the presence of 12 mL triethyl amine (11.569 mL,
83.002 mmol). The mixture was continuously stirred for 30 minutes at room temperature,
under a nitrogen atmosphere. The resulting solution was filtered and the solvent was removed
under vacuum to yield an oily, colourless crude product, which quickly solidified. The white
solid was suspended in water and filtered off, washed with diethyl ether and then dried under
vacuum. Yield: 93.0%, m.p.: 177.1 °C. Anal. Calcd for C12H15NO3 (%): C, 65.14; H, 6.83; N,
6.33. Found: C, 65.12; H, 6.78; N, 6.27. IR (cm-1): v(N-H) 3252(s); v(C-H) 3060, 2980,
1
2936(w); v(C=O) 1763, 1688(s); v(C=C) 1525(s); v(C-O-C) 1298–1176(m). H NMR (400
MHz, DMSO-d6, δ ppm): 1.33 (t, J = 6.97 Hz, 3H), 2.14 (s, 6H), 4.31 (q, J = 7.17 Hz, 2H),

7.11 (m, 3H), 10.29 (br s, 1H). 13C NMR (400 MHz, DMSO-d6, δ ppm): 14.34, 18.36, 62.73,
127.64, 128.27, 134.09, 135.59, 156.25, 161.32.
2.6.
Synthesis of complexes 1–4
A mixture of 3 mL 1M NaOH and Hdmp (≈3 mmol) was heated until the ligand dissolved.
An aqueous solution of 1 mmol [Ln(NO3)3∙xH2O] (Ln = Ce, Nd, Gd and Er) was mixed with
the ligand solution. The resulting white precipitate was filtered, washed with distilled water
and diethyl ether, and then dried. Dissolution in methanol, followed by slow diffusion of
diethyl ether into the solution resulted in X-ray quality crystals within 5 days (Scheme 2).
2.6.1. {[Ce(Hpma)3(MeOH)(H2O)]∙2MeOH}n
(1)
Hdmp (0.664 g, 3 mmol), 1 M NaOH (3 mL), [Ce(NO3)3∙6H2O] (0.434 g, 1 mmol). Yield:
0.536 g (64.5% based on the Ce(III) salt); white crystals, m.p.: > 300.0 °C. Anal. Calcd. for
C31H36CeN3O11, 2(CH4O) (%): C, 47.71; H, 5.34; N, 5.06. Found: C, 47.63; H, 5.19; N, 5.26.
Conductivity (10-3 M, DMF, ohm-1 cm2 mol-1): 3.55. IR (cm-1): v(O-H) 3613–3125(b); v(C-H)
3052–2931(w); v(C=O) 1635(s); v(Ln-O) 447(w).
2.6.2. {[Nd(Hpma)3(MeOH)(H2O)]∙2MeOH}n
(2)
Hdmp (0.662 g, 2.992 mmol), 1 M NaOH (3 mL), [Nd(NO3)3∙6H2O] (0.437 g, 0.997 mmol).
Yield: 0.531 g (63.7% based on the Nd(III) salt); purple crystals, m.p.: > 300.0 °C. Anal.
Calcd. for C31H35NdN3O11, 2(CH4O) (%): C, 47.53; H, 5.20; N, 5.04. Found: C, 47.45; H,
5.18; N, 5.07. Conductivity (10-3 M, DMF, ohm-1 cm2 mol-1): 3.58. IR (cm-1): v(O-H) 3613–
3125(b); v(C-H) 3052–2931(w); v(C=O) 1635(s); v(Ln-O) 450(w).
2.6.3. {[Gd2(Hpma)6(MeOH)4]∙6MeOH}n
(3)
Hdmp (0.663 g, 2.996 mmol), 1 M NaOH (3 mL), [Gd(NO3)3∙6H2O] (0.452 g, 1.001 mmol).
Yield: 0.497 g (55.6% based on the Gd(III) salt); white crystals, m.p.: > 300.0 °C. Anal.
Calcd. for C64H76Gd2N6O22, 6(CH4O) (%): C, 47.02; H, 5.64; N, 4.70. Found: C, 47.12; H,
5.48; N, 4.82. Conductivity (10-3 M, DMF, ohm-1 cm2 mol-1): 14.45. IR (cm-1): v(O-H) 3613–
3125(b); v(C-H) 3052–2929(w); v(C=O) 1635(s); v(Ln-O) 447(w).
2.6.4. {[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n
(4)

Hdmp (0.664 g, 3 mmol), 1 M NaOH (3 mL), [Er(NO3)3∙5H2O] (0.443 g, 0.999 mmol).
Yield: 0.578 g (70.6% based on the Ce(III) salt); pink crystals, m.p.: 278.3 °C. Anal. Calcd.
for C61H70Er2N6O22, 2(CH4O) (%): C, 46.20; H, 4.80; N, 5.13. Found: C, 46.48; H, 4.74; N,
5.33. Conductivity (10-3 M, DMF, ohm-1 cm2 mol-1): 51.90. IR (cm-1): v(O-H) 3613–3125(b);
v(C-H) 3052–2929(w); v(C=O) 1637(s); v(Ln-O) 447(w).
2.7.
Synthesis of complexes 5 and 6
A mixture of 3 mmol Hdmp dispersed in water and 3 mL 1M NaOH was heated until the
ligand dissolved. A 1 mmol [Ln(NO3)3∙6H2O] (Ln = Nd and Gd) aqueous solution was added
to the ligand solution, and a white precipitate formed. The mixture was refluxed, and then
methanol was added until the precipitate dissolved. The solution was cooled and kept at room
temperature until single crystals formed after 7 days.
2.7.1. [Nd2Na2(Hpma)8(EtOH)(H2O)6]n
(5)
Hdmp (0.666 g, 3.010 mmol), 1 M NaOH (3 mL), [Nd(NO3)3∙6H2O] (0.438 g, 1 mmol).
Yield: 0.489 g (48.3% based on the Nd(III) salt); purple crystals, m.p.: 276.8 °C. Anal.
Calcd. for C82H95.54N8Na2Nd2O30.46, C2H6O, O (%): C, 48.58; H, 4.93; N, 5.40. Found: C,
48.51; H, 4.68; N, 5.79. Conductivity (10-3 M, DMF, ohm-1 cm2 mol-1): 46.90. IR (cm-1): v(O-
H) 3613–3125(b); v(C-H) 3052–2929(w); v(C=O) 1635(s); v(Ln-O) 452(w).
2.7.2. [Gd2Na2(Hpma)8(EtOH)(H2O)6]n
(6)
Hdmp (0.660 g, 2.978 mmol), 1 M NaOH (3 mL), [Gd(NO3)3∙6H2O] (0.453 g, 1 mmol).
Yield: 0.493 g (48.2% based on the Ce(III) salt); white crystals, m.p.: 277.5 °C. Anal. Calcd.
for C81.41H94.22Gd2N8Na2O30.30, C2H6O, O (%): C, 47.89; H, 4.83; N, 5.36. Found: C, 47.84;
H, 4.67; N, 5.35. Conductivity (10-3 M, DMF, ohm-1 cm2 mol-1): 53.40. IR (cm-1): v(O-H)
3613–3125(b); v(C-H) 3052–2929(w); v(C=O) 1636(s); v(Ln-O) 447(w).
3.
Results and discussion
3.1.
Synthesis, FT-IR and NMR spectroscopy
The use of basic media in the preparation of the coordination compounds resulted in the
conversion of the proligand Hdmp to the anionic Hpma– [38].

The infrared spectra of the proligand Hdmp and its Ln(III) complexes (Figure 2) exhibit
similar spectral features due to their related coordination environments [39]. The strong v(N-
H) band of Hdmp located at 3252 cm-1 is replaced by broad bands in 1–6 in the region 3613–
3125 cm-1, indicating the presence of O-H stretching vibrations of water or methanol
molecules in the metal complexes [38,40,41]. The high frequency spectral region of the
proligand Hdmp also exhibits typical C-H vibrations (3060, 2980 and 2936 cm-1), while the
C-H vibrations of the phenyl rings of the oxamate ligands in the complexes show a slight red-
shift (3052–2929 cm-1) relative to Hdmp [38]. Two strong absorptions occurring at 1763 and
1688 cm-1 correspond to the characteristic C=O stretching vibrations in Hdmp [38,42]. These
strong v(C=O) appear as single bands in all the title complexes, at approximately 1635 cm-1,
hence confirming the role of the oxamate oxygen atoms in coordination [38,42]. A series of
four absorption peaks in the range 1298–1176 cm-1, typical of C-O-C bonds, are observed for
the free ligand. The latter disappear upon coordination, thus confirming the complete
conversion of Hdmp to Hpma– [40]. After complexation, weak Ln-O vibrations are assigned
to the bands found at 452–447 cm-1, which show the involvement of the oxygen atoms in the
primary coordination sphere of the lanthanide(III) ions [40,43].
Nuclear magnetic resonance experiments on Hdmp and the complexes were performed in
DMSO-d6 (Figure 3). For complexes 3, 4 and 6, the paramagnetic nature of the Gd(III) and
Er(III) ions gave rise to signal broadening and featureless 1H NMR spectra, while complexes
1, 2 and 5 gave clearly defined spectra, though there appears discernible evidence of some
broadening [44]. In concurrence with the IR spectral and X-ray crystallographic data, the 1H-
NMR spectra of the coordination compounds 1, 2 and 5 clearly show formation of the Hpma–
anion from Hdmp, as indicated by the disappearance of the ethyl group signals after
coordination [38]. The N-H group peaks of the ligand gives a broad signal in 1 (δ 12.29
ppm), but similar peaks are not seen in the spectra of 2 and 5, suggesting participation of the
oxamate moieties in ligand coordination [38]. The spectra of the complexes also exhibit
Hpma– methyl proton signals, peaking at δ 1.55, 1.57 and 1.51 ppm, an indication that the
methyl groups undergo a significant shift in the chemical environment relative to Hdmp (δ
2.14 ppm) upon hydrolysis [45]. Downfield to the methyl proton peaks of 1, 2 and 5, are
resonances attributable to the aromatic proton signals of the oxamate ligands (δ 6.37–6.57
ppm), which are also more shielded than the proligand aromatic protons (δ 7.11 ppm).

3.2.
UV-Vis-NIR spectroscopy
The ligand Hdmp and the trivalent complexes of Ce(III) and Gd(III) (complexes 1 and 3)
have no significant absorption in the ultraviolet, visible and near-infrared regions. The UV-
Vis-NIR spectra of 2, 4, 5 and 6 are displayed in Figure 4 and the assignment of absorption
bands is shown in Table 2. Absorption peaks of the Nd(III), Er(III) and Gd(III) complexes
4
4
8
arise from the Laporte-forbidden f-f transitions from the ground level of I9/2, I15/2 and S7/2,
respectively, to the excited J-levels of the 4f-configuration [46-51]. The spectra of 2 and 5 are
similar, with absorption maxima at 511, 522, 582 and 745 nm in the visible region,
4
4
4
corresponding to transitions from the I9/2 ground level to the excited J-levels G9/2, G7/2,
4G5/2 + 2G7/2 and 4F7/2 + 4S3/2, respectively [46-48,51,52]. The peak observed in the NIR region
at 800 nm is assigned to the f-f transition from the ground level to the 4f-configurations 4F5/2
2
4
+ H9/2, while those appearing at 869 and 876 nm are attributed to a transition from I9/2 to
4F3/2. The Er(III) complex 4 shows the most intense bands positioned at 379 and 522 nm that
are due to the transitions 4I15/2→4G11/2 and 4I15/2→2H11/2 [49,53-55].
3.3.
Coordination geometry analysis
The geometries of the NaO5, NaO6, LnO9 and LnO8 coordination polyhedra of the lanthanide
complexes with Hpma– were evaluated by continuous shape measures using SHAPE 2.1
software, for quantification of the degree of distortion of the Ln(III) coordination geometry
(Table 3). The polyhedral data generated using VESTA are presented in Figure 5. For all the
coordination compounds, there are no significant distortions from the ideal polyhedra (CShM
values ≤ 3) [56-58]. The shape analysis of the nine-coordinate complexes 1 and 2 highlight
the coordination geometry of the distorted spherical tricapped trigonal prism (TCTPR-9),
with D3h symmetry [59,60]. The Nd(III) complex 2 is closer to the TCTPR-9 geometry than
complex 1 with the larger metal Ce(III) ion. The continuous shape measures obtained for the
spherical capped square antiprism (CSAPR-9) shape in 1 (CShM = 0.92568) and 2 (CShM =
0.82770), however, exhibit a small difference from the TCTPR-9 geometry [61]. Hence, the
coordination spheres of 1 and 2 can be considered as the intermediate between CSAPR-9 and
TCTPR-9 geometries [61,62]. The coordination polyhedron of the octa-coordinated Er1 atom
of 4 can be viewed as a square antiprism (SAPR-8), with a deviation parameter from the ideal
SAPR-8 of 0.43454 [56].

The least CShM parameters for the nine-coordinate Ln(III) ions of 3–6 indicate the distorted
CSAPR-9 geometry (C4v). Despite having a similar coordination environment, the Gd(III)
coordination polyhedra in 3 display a small difference in CShM values. Distortion parameters
are in the order Nd(III) > Gd(III) > Er(III). The other closest geometries for Nd1 (complex 5)
and Gd1 (complex 6) is TCTPR-9, with deviation values of 0.98091 and 0.86226,
respectively; while that of Gd2 (complex 6) is a muffin geometry (MFF-9) (CShM =
0.93876) [59,61,62]. In addition, the oxygen atoms around the hexa-coordinate Na cations in
5 and 6 form two square-based pyramids, adopting an octahedron (OC-6) shape (CShM
values of 1.90099 and 2.08861, respectively), whereas the geometry of the five-coordinate Na
ions can be described as vacant octahedron (vOC-5), possessing C4v symmetry [63,64].
There is a better fit to the ideal polyhedra as the atomic number of the 4f elements increase,
as evidenced by the smaller shape measure values. This is due to the shorter and stronger
bonds, as well as decreased room for angular distortions as the metal ions decrease in size
[57]. The volume of the coordination polyhedra is controlled by the size of the metal ions, as
well as the coordination numbers. Smaller metal ions and lower coordination numbers result
in smaller polyhedral volumes. A comparison between the Ln(III) coordination environments
of all the complexes reflect the highest polyhedral volume for the nine-coordinate Ce(III)
compound (32.4845 Å3), and the smallest polyhedron size for the eight-coordinate Er1 in 4
(22.5763 Å3).
3.4.
Crystal structures and hydrogen bonding
The reactions in aqueous mixtures between the lanthanide nitrate salts and Hdmp (Figure 6a),
in the presence of NaOH, yield interesting Ln(III)–organic coordination polymers, formulated
as:
{[Ln(Hpma)3(MeOH)(H2O)]∙2MeOH}n
(Ln
=
Ce
and
Nd),
and
{[Gd2(Hpma)6(MeOH)4]∙6MeOH}n,
{[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n
[Ln2Na2(Hpma)8(EtOH)(H2O)6]n (Ln = Nd and Gd) (Figures 6b-e; see Tables 4a and 4b for
bond parameters). X-ray diffraction studies of the single crystals revealed that the
isostructural complexes 1 and 2 crystallise in the monoclinic space groups I2/a, whereas
complexes 3–6 give the triclinic crystal structure, belonging to the P-1 space group.
Complexes 5 and 6 are also structurally analogous to each other. The polymeric complexes

feature Ln-Hpma moieties bridged by Hpma–, giving one-dimensional (1D) zig-zag chains of
the –Ln–O–C–O–Ln– type, with the Ln⋯Ln separation varying from 6.271 Å (complex 2) to
6.843 Å (complex 5), thus showing well isolated mononuclear units (Figure 6f) [65-67]. The
chelating and bridging modes of Hpma– via only the oxygen atoms are indicated in Figure 6g
[68-70].
Three bidentate Hpma– ligands, one methanol and one water molecule form the mononuclear
units of 1 and 2, which are connected through the fourth bridging oxamate ligand (Figure 6b).
Complexes 1 and 2 have voids, with the voids of 1 having too little electron density to model
anything, whereas the voids of 2 may contain one or two water molecules but are too
extensively disordered over a large volume to model. The Ce(III) and Nd(III) ions are nine-
coordinate with the oxygen atoms bonded to form a distorted spherical tricapped trigonal
prism geometry. Furthermore, there are two non-coordinating methanol molecules present in
the lattices.
Complex 3 is characterised by dinuclear units containing similar spherical capped square
antiprism GdO9 cores, with each nona-coordinate environment constructed from three
chelating Hpma– ligands, two methanol molecules and one oxygen atom from the bridging
(tridentate) Hpma– ligand (Figure 6c). Complex 4 gives metal centres comprising distinct
Er(1)O8 (SAPR-8) and Er(2)O9 (CSAPR-9) cores linked by chelating/bridging Hpma– ligands
(Figure 6d). The Er1 coordination sphere is made up of three bidentately coordinated Hpma–
ligands and two water molecules, whilst the nine-coordinate Er2 ion is surrounded by three
η2-bonded oxamates, one methanol, one water molecule and an O-atom from the tridentate
Hpma–. In addition, the metal complexes 3 and 4 feature lattice methanol solvates (six for
complex 3 and two for complex 4).
Coordination compounds 5 and 6 yielded lanthanide(III)-sodium(I) complexes, with Ln2Na2
(Ln = Nd and Gd) cores bridged by the μ2-η1:η1:η1, μ3-η1:η2:η1 and μ2-η1:η2 oxamate ligands,
as well as by the μ2-H2O oxygen atoms (Figures 6e and 6h) [68-70]. The asymmetric unit
contains two nine-coordinate Ln(III) ions with the CSAPR-9 geometry. Complexes 5 and 6
also contain voids with enough electron density to contain one ethanol and water molecule
(and their inversion symmetries). One extensively disordered ethanol molecule has been
modelled. The Ln1 atom is surrounded by three η2 Hpma–, two O-atoms from the bidentately
coordinated μ2-η1:η2 Hpma– and one oxygen provided by μ3-η1:η2:η1 bonded Hpma–, whereas

the O9 donor-set of Ln2 is fulfilled with six oxygen atoms from O,O-donor oxamate ligands
(O52, O53, O61, O62, O71, O72), two oxygen atoms from a bridging Hpma– and a μ2-O
bridging water molecule. Each Na1 is in a hexa-coordinate environment, linked to four μ2-O
atoms of water, and two oxygen atoms from the μ2-η1:η2 and the μ3-η1:η2:η1 Hpma–, while the
vacant octahedron geometry of Na2 is constructed from five O-atoms (two H2O molecules,
one μ2-Owater, one disordered ethanol and one bridging oxygen of Hpma–). The crystal
structures of the heterometallic complexes feature rhomboidal Ln-O-Na-O cores, where
bridging occurs through the O-atoms of Hpma– and water molecules, having bridging oxygen
atoms lying almost equidistant between the metal ions [the M-OHpma- and M-Owater (M = Nd,
Gd and Na) bonds vary from 2.3771(16) to 2.469(2) and from 2.5143(16) to 2.566(2) Å,
respectively] [71]. The O-M-O, Ln-Owater-Na and Ln-OHpma--Na bond angles in these
rhomboids are in the ranges 65.85(6)–67.01(5), 107.63(7)–108.05(7) and 117.17(8)–
117.20(7) °, respectively. The Ln-Owater-Na bond angles do not display any anomalies and
compare well with the 108.66(9) ° Gd–O–Gd angle in [Gd2(bfa)4L2]CH2Cl2 (bfa =
benzoyltrifluoroacetone and HL = 2-[[(4-methylphenyl)imino]methyl]-8-hydroxyquinoline)
[72]. The Na(I) ions are connected to each other via the water oxygen atoms, with Na1–
Owater–Na2 angles of 120.31(9) ° (complex 5) and 121.16(8) ° (complex 6).
All the metal complexes are comprised of bidentately (η2) coordinated Hpma– ligands,
leading to five-membered chelate rings with O-Ln-O angles of 63.51(4)–69.80(6) ° and Ln-
OHpma- distances of 2.2722(18)–2.4752(12) Å, which are comparable to those in the
previously reported dysprosium(III) complex containing N-(2,6-dimethylphenyl) oxamic acid
[Dy-O bond lengths = 2.340(2)−2.407(2) Å; O-Dy-O bite angles = 67.36(8) to 68.04(7) °]
(Tables 4a and 4b) [15]. The shortening of the C4-O2 bond [1.3138(17) Å] of Hdmp in the
complexes [e.g. O12-C19 = 1.2564(19) Å in 1] suggest a double bond character in the Hpma–
ligand , as a result of delocalisation across the oxamate moiety [73]. The Ln-Owater and Ln-
OMeOH distances, spanning the ranges 2.3369(19)–2.5049(13) and 2.391(2)–2.5404(12) Å,
respectively,
are
similar
to
those
in
the
triaqua[2,6-diacetylpyridine
bis(benzoylhydrazone)]methanol-lanthanide(III) complexes reported by Kachi-Terajima et al.
(2018) [Ln-Owater = 2.313(2)–2.428(2) and Ln-OMeOH = 2.472(2)–2.4867(18) Å, Ln = Tb and
Dy] [74]. The Na-Ooxamate bond lengths of 5 and 6 [spanning the range 2.336(2)–2.476(2) Å],
compare well with the bond parameters of the alkaline salts of bis(oxamato)palladate(II)
complexes reported by Fortea-Pérez et al. (2014) [Na-Ooxamate = 2.273(5)–2.909(5) Å] [75]. A

decrease in the Ln-O distances with increasing atomic number is observed, as expected due to
the result of the lanthanide contraction [66,70,76].
The crystal structures of 1–6 are further stabilised by networks of medium strength hydrogen
bonds of the N-H⋯O and O-H⋯O type, as presented in Figure 6i and Table 4c [59,77-79].
Only intermolecular N-H⋯O bonds [H⋯O = 2.232(17)–2.408(17) Å] are found in the
proligand, which are satisfied by the amide N-H groups of one molecule and the oxygen
atoms of the oxamate group from a neighbouring molecule. It is important to note that these
hydrogen bond interactions in the metal complexes involve the crystallographic methanol
solvent molecules and have DA (Donor⋯Acceptor) distances in the range 2.644(3)–3.183(3)
Å. N-H⋯O bonds are apparent between the amide N-H (donor) and the solvent molecules or
the O-atoms of Hpma– as acceptors. As observed in 1 and 2, the two lattice methanol solvent
molecules, along with the coordinated water and the bonded oxygen atoms of Hpma–, play a
key role in establishing O-H⋯O interactions. In 3, the methanol molecules in the primary and
secondary coordination spheres act as donors, assuring connectivity with the oxygen atoms of
the oxamate ligands. As shown in Figure 6i, the coordinated water molecules of 4 form
hydrogen bonds with the lattice methanol molecules, for example O2-H2A⋯O5 with a DA
distance of 2.663(3) Å. The crystal structures of the heterometallic complexes 5 and 6 are
also stabilised by a variety of hydrogen bonds, some of which involve monodentate and
bridging water molecules as hydrogen donors and oxamate oxygen atoms as acceptors. The
crystal packing of the metal complexes is supplemented by weak contacts: C-HHpma–∙∙∙OHpma–
(1–6), C-HMeOH∙∙∙OHpma– (2–4), C-HHpma–∙∙∙OMeOH (3), C-HMeOH∙∙∙OMeOH (4), C-HHpma–∙∙∙OH O
2
(5), as well as C-HHpma–∙∙∙NHpma– (5 and 6) [80].
3.5.
Atomic charge analysis of the ligand and MEP surface
The total atomic charges of the anionic oxamate ligands were determined by the NPA
method, and are presented in graphical form, shown in Figure 7b (see Figure 7a for atom-
numbering) [81]. According to the NPA method, the obtained atomic charges indicate that
the C22, C23 and H24 atoms have larger positive atomic charges compared to the other
hydrogen atoms. Atoms O1, O2 and O3 exhibit the most negative atomic charges (-0.6720, -
0.76420 and -0.79536 in DMSO). Natural population analysis predicted the same tendencies
on the net atomic charges of the aforementioned atoms in the gas phase, with the charges on

O1, O2 and O3 being -0.63226, -0.70104 and -0.78570, respectively. This explains the ability
of the atoms to network with the positively-charged component, with O3 having a stronger
coordination ability to form stronger (shorter) Ln-O bonds [82]. The calculated results thus
concur with most of the experimental Ln-Ooxamate results obtained through the X-ray
diffraction studies. The nitrogen atom N4 displays an electronegativity (-0.63544 in DMSO
and -0.67626 in the gas phase) lower than that of the oxygen atoms. The electronegative O-
atoms therefore have the tendency to donate electrons, while the electropositive carbon and
hydrogen atoms have a tendency to accept electrons [81,83,84]. The presence of large
negative charges on the oxygen and nitrogen atoms, and positive charges on the hydrogen
atoms suggest the possibility of intermolecular interactions in the crystal structure [85].
The accrual of charges on selected atoms and the distribution of electrons in the core, valence
and Rydberg sub-shells of Hpma−, are shown in Table 5. Furthermore, NPA in solvent shows
that 102 electrons in the ligand have the sub-shell distributions as follows:
Core:
27.99986 (99.9995% of 28)
Valence: 73.60526 (99.4666% of 74)
Rydberg: 0.39488 (0.3871% of 102)
Molecular electrostatic potential (MEP) mapping was applied in the interpretation and
prediction of the reactive behaviour of Hpma– in nucleophilic and electrophilic reactions, as
well as in depicting the shape of the oxamate ligand (Figure 7c) [81,86]. This is important in
predicting chemical reactivities in hydrogen bond interactions and biological systems [26].
The oxygen atoms of Hpma– are associated with a strong negative molecular electrostatic
potential region. The concentration of maximum electron density on the oxygen atoms
enables interaction with trivalent metal ions to form O,O-donor chelates, as well as the
participation of the remaining O-atom in bridging. In addition to bonding with Ln(III) ions,
the MEP region around the oxygen atoms suggest that these oxygen atoms can also act as
hydrogen bond acceptors, which is consistent with the X-ray analysis. The nitrogen atom
comparatively possesses a smaller negative MEP region.
3.6.
Global and chemical reactivity descriptors

Some of the most imperative parameters for biological chemistry, chemical reactivity and
drug design, like the HOMO, LUMO and the HOMO-LUMO gaps of Hpma–, were calculated
using the basis set B3LYP/aug-cc-pVTZ and visualised from the computed data using
Avogadro software (Figure 8 and Table 6) [87]. The HOMO, HOMO-1 (second highest) and
HOMO-2 (third highest) energies in order are -6.233, -6.554 and -6.654 eV, whereas the
LUMO, LUMO+1 (second lowest) and LUMO+2 (third lowest) were calculated to be -0.784,
-0.339 and -0.245 eV, respectively. The observed energy gaps pertaining to the energy
needed to achieve electronic transitions between the HOMO–LUMO, HOMO-1–LUMO+1
and HOMO-2–LUMO+2 are 5.449, 6.215 and 6.409 eV, respectively. These energy gaps play
an important role in the elucidation of the chemical stability of a molecule, with a highly
stable molecule depicted by a high energy gap, and a low energy gap being typical of high
reactivity [87,88]. The ionisation potential (I = –EHOMO = 6.233 eV) and electron affinity (A =
–ELUMO = 0.784 eV) are predictable from the HOMO and LUMO energy values [87].
Global reactivity descriptors, such as chemical potential (μ), hardness (η), softness (σ),
electrophilicity index (ω) and electronegativity (χm), were determined by resorting to the
ionisation potential and electron affinity obtained from the HOMO and LUMO energies, with
the results being μ = -3.509 eV, η = 2.725 eV, σ = 0.367 eV-1, ω = 2.259 eV and χm = 3.509
eV [87,88]. These parameters are an efficient tool in providing theoretical insights into the
biological activity and behaviour of the whole chemical species when the compound enters
the body as an anticancer drug [89,90]. Calculations for the local reactivity parameters:
electrodonating (ω−) power, electroaccepting (ω+) power and the net electrophilicity (Δω±),
are also included (Table 6) to provide information regarding the behaviour of specific sites in
the molecule, which is crucial in reactivity elucidation and selectivity trends [91-93]. The
electrodonating power (ω− = 4.354 eV) shows the propensity to donate charge, whereas the
electroaccepting capacity (ω+ = 0.845 eV) indicates the tendency of a system to accept
charge; with the ω− value of the molecule being more important than its electroaccepting
ability [92-94]. The net electrophilicity (electron-accepting ability relative to its electron-
donating capacity) is equal to 5.199 eV [95].
3.7.
Anticancer studies

The viability of MCF-7, HEC-1A and THP-1 cells was determined after exposure to 100 μM
of the proligand Hdmp, Ln(III) nitrate salts, Ln(III) oxamate complexes and curcumin, for 24
hours. As shown in Figure 9, the results indicate that when exposed to [Ce(NO3)3∙6H2O], the
cell viability of the MCF-7 cells decreased (p < 0.05). Likewise, [Nd(NO3)3∙6H2O] exerted
cytotoxic effects in HEC-1A cells (p < 0.05). The cytotoxicities of Hdmp, [Ln(NO3)3∙xH2O]
(Ln = Gd and Er) and metal complexes 1–6 were also tested against the three cell lines for
comparison, but no significant cytotoxicity was noted (p > 0.05).
The greatest cytotoxic effect was observed after exposure to curcumin, which decreased cell
viabilities to 46.8±6.46, 14.1±3.76 and 21.5±0.83% for MCF-7, HEC-1A and THP-1 cells,
respectively. The cytotoxicity of curcumin is explicated by its ability to regulate multiple cell
signalling pathways, such as cell proliferation, senescence, apoptosis and the protein kinase
pathway [34,96].
For each assay, the viability of the THP-1 cells treated with the proligand, lanthanide salts
and the coordination compounds were not significantly affected, suggesting no adverse
effects on THP-1 cell line counterparts, i.e. primary monocytes or human peripheral blood
monocytes (Figure 9) [97-99]. This, however, needs to be validated by further in vitro and in
vivo studies.
4.
Summary
Syntheses of six novel oxamates of trivalent rare-earth metals (Ce, Nd, Gd and Er) in basic
media have been successfully reported. The compositions and structures of these polymeric
complexes have been characterised by elemental analyses, conductivity measurements, IR,
UV-Vis-NIR, NMR and X-ray diffraction studies. The X-ray crystallography results indicate
that the Hpma– ligand possesses a variety of chelating and bridging modes, displayed by the
three oxygen atoms. The units of 1–4 contain lattice methanol molecules, which afford
oxygen atoms needed in the formation of some O-H⋯O links. The oxamate ligands adopt the
μ2- and μ3-bridging modes, generating one-dimensional coordination polymers. In the
heterometallic polymers 5 and 6, interconnection of Ln(III) and Na(I) ion centres is also
supplemented by μ2-bridging water molecules. The experimental bond parameters were in
excellent agreement with related compounds in the literature.

Using the B3LYP/aug-cc-pVTZ level, NPA of N-(2,6-dimethylphenyl)oxamate has been
performed to evaluate partial atomic charges. The HOMO and LUMO energies, as well as the
MEP surfaces, assisted in determining the chemical reactivity of the title anionic ligand.
Partial atomic charges and MEP surfaces of the oxamate ligand are corroborated by the
crystal data.
An MTT assay was employed to determine MCF-7, HEC-1A and THP-1 viability after
exposure to 100 µM of the compounds, by determining the reduction of MTT to formazan
crystals. Although no evidence of cytotoxicity was observed for the title complexes, the rare-
earth metal salts [Ce(NO3)3∙6H2O] and [Nd(NO3)3∙6H2O] showed modest cytotoxicity against
MCF-7 and HEC-1A cells, respectively. Complexes 2 and 3 also show cytotoxicity against
HEC-1A. These results indicate that these two metal salts could be potential starting materials
in the development of anticancer agents. Further attempts will be concentrated on the
preparation of other complexes from Hdmp or Hpma– derivatives.
Acknowledgements
Funding from the National Research Foundation (unique grant number: 106004) and Nelson
Mandela University Postgraduate Research Scholarship is gratefully acknowledged. The
authors would like to thank the Centre for High Performance Computing of South Africa, for
allowing access to usage of computational resources to execute this research. The authors
also thank the supportive experimental assistance of Mr Kwakhanya Mkwakwi, Mr Cameron
Matthews and Mr Cyprian Moyo from Nelson Mandela University.
Appendix A. Supplementary data
Crystallographic data for the reported complexes have been deposited at the Cambridge
Crystallographic Data Centre with CCDC reference numbers 1985517–1985523. These data
are available from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK on request or can be
obtained free of charge from the Cambridge Crystallographic Data Center via
https://www.ccdc.cam.ac.uk/data_request/cif.

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Lanthanide complexes with N-(2,6-dimethylphenyl)oxamate:
Synthesis, characterisation and cytotoxicity
Tatenda Madanhire, Hajierah Davids, Melanie C. Pereira, Eric C. Hosten and Abubak’r Abrahams*
Email: Abubakr.Abrahams@mandela.ac.za
School of Biomolecular and Chemical Sciences, PO Box 77000, Nelson Mandela University,
Port Elizabeth, 6031, South Africa
ABSTRACT

Table 1: Crystal and structure refinement data for Hdmp and 1–6.
Compound
Hdmp
1
2
3
Formula
C12H15NO3
C31H36CeN3O11,
2(CH4O)
830.83
Monoclinic
I2/a (No. 15)
C31H36NdN3O11,
2(CH4O)
834.95
Monoclinic
I2/a (No. 15)
C64H76Gd2N6O22, 6(CH4O)
Mr (g.mol-1)
Crystal system
Space group
221.25
Orthorhombic
Pbca (No. 61)
1788.05
Triclinic
P-1 (No. 2)
a, b, c [Å]
8.8959(4), 8.0239(3),
32.9010(14)
22.8156(9),
12.5043(5),
27.7448(11)
90, 93.288(3), 90
22.7183(18),
12.4573(11),
27.852(2)
11.7874(5), 17.7660(8),
21.0024(10)
α, β, γ (°)
90, 90, 90
90, 92.929(6), 90
73.394(2), 78.014(2),
80.235(2)
4094.3(3)
2
1.450
1.685
V (Å3)
Z
2348.47(17)
8
1.252
0.090
7902.4(5)
8
1.397
1.214
7872.1(11)
8
1.409
1.381
ρ (g cm-3)
µ (mm-1)
F(000)
944
3400
3416
1828
Crystal size (mm)
0.17 × 0.24 × 0.61
0.09 × 0.16 × 0.37
0.18 × 0.39 × 0.69
0.06 × 0.30 × 0.50
θ (min-max) (°)
2.5, 28.3
1.8, 28.3
2.3, 28.4
1.2, 28.4
Data set
-11≤h≤11; -10≤k≤10;
-43≤l≤43
-30≤h≤26; -16≤k≤16;
-36≤l≤37
-29≤h≤30; -16≤k≤16;
-37≤l≤37
-15≤h≤15; -23≤k≤23;
-27≤l≤28
Tot., Unique data, Rint 62507, 2927, 0.025
90084, 9810, 0.025
55211, 9815, 0.018
92833, 20449, 0.030
Observed [I>2σ(I)]
2530
8693
8839
16558
reflections
Nreflections, Nparameters
R[F2>2σ(F2)],
wR(F2), S
2927, 152
0.0499, 0.1309, 1.12
9810, 486
0.0186, 0.0456, 1.06
9815, 486
0.0241, 0.0726, 1.14
20449, 1023
0.0282, 0.0650, 1.08
Δρmin, Δρmax (e.Å-3)
-0.19, 0.31
-0.47, 0.83
-0.85, 1.49
-0.93, 2.10
Compound
4
5
6
Formula
C61H70Er2N6O22,
2(CH4O)
1637.83
Triclinic
P-1 (No. 2)
C82H95.54N8Na2Nd2O30.46
C2H6O, O
2077.02
Triclinic
P-1 (No. 2)
,
C81.41H94.22Gd2N8Na2O30.30
C2H6O, O
2092.04
Triclinic
P-1 (No. 2)
,
Mr (g.mol-1)
Crystal system
Space group
a, b, c [Å]
14.5404(7), 14.9104(7), 11.4098(6), 20.9380(11),
11.3308(5), 20.7995(10),
19.1140(9)
21.5456(11)
21.5254(10)
α, β, γ (°)
106.487(2), 95.985(2),
111.678(2), 93.897(3),
111.771(2), 93.982(2),
116.654(2)
3419.2(3)
2
1.591
2.519
99.470(3)
4671.2(4)
2
1.477
1.193
98.973(2)
4608.5(4)
2
1.508
1.522
V (Å3)
Z
ρ (g cm-3)
µ (mm-1)
F(000)
1652
2126
2130
Crystal size (mm)
θ (min-max) (°)
Data set
0.11 × 0.41 × 0.70
1.6, 28.4
-19≤h≤18; -13≤k≤19;
-25≤l≤25
0.11 × 0.25 × 0.32
1.7, 28.3
-15≤h≤15; -27≤k≤27;
-28≤l≤28
0.26 × 0.36 × 0.64
1.8, 28.4
-15≤h≤15; -27≤k≤27;
-28≤l≤28
Tot., Unique data, Rint
Observed [I>2σ(I)]
reflections
61425, 17016, 0.018
15123
168732, 23318, 0.039
18870
328132, 22936, 0.022
20375
Nreflections, Nparameters
17016, 924
0.0204, 0.0472, 1.15
23318, 1221
0.0292, 0.0740, 1.03
22936, 1227
0.0242, 0.0626, 1.14
R[F2>2σ(F2)], wR(F2), S