Facile high-yield synthesis of unsymmetric end-off compartmental double Schiff-base ligands: Easy access to mononuclear precursor and unsymmetric dinuclear complexes

Article abstract of DOI:10.1039/c6ra16870a

A straightforward and easy to handle two-step synthetic route for unsymmetric double Schiff-base ligands is presented. The isolated intermediate single Schiff-base precursor ligands H₂sc-difo and H₂tsc-difo were derived by condensation of 2,6-diformyl-4-methylphenol with semicarbazide and thiosemicarbazide, respectively. Further reaction of the precursor ligands with different amine components, including both aliphatic and aromatic examples, allows the synthesis of ditopic unsymmetric double Schiff-base ligands in high yields and purity. As aliphatic cases we used (2-aminoethyl)bis(2-pyridylmethyl)-amine (H₂sc-hydra and H₂tsc-hydra) and 2-(aminomethyl)-pyridine (H₂sc-ampy and H₂tsc-ampy), whereas 2-aminophenol was used as an aromatic sample (H₃sc-amph and H₃tsc-amph). The overall synthetic route allows for the preparation of the employed ligands in large scale. To explore the coordination capabilities of the reported ligand systems a mononuclear nickel(ii) complex [Ni(tsc-difo)PPh₃] and a homodinuclear zinc(ii) complex [Zn₂(tsc-hydra)(OAc)₂] were synthesized with the single Schiff-base precursor ligand H₂tsc-difo and the double Schiff-base ligands H₂tsc-hydra, respectively. Both complexes crystallized in the monoclinic space group P2₁/n. For [Ni(tsc-difo)PPh₃] a square-planar geometry is found for nickel(ii) ion with H₂tsc-difo acting as a tridentate ligand. Whereas the structure of complex [Zn₂(tsc-hydra)(OAc)₂] reveals two zinc(ii) ions in distinctly different coordination geometry, one in distorted octahedral coordination located in the bispyridine based binding pocket with [N₄O₂] donor set and the other zinc(ii) ion in a distorted square-pyramidal coordination given by the thiosemicarbazone based binding pocket with [NO₃S] donor set.

Full text of DOI:10.1039/c6ra16870a

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Facile high-yield synthesis of unsymmetric end-off
compartmental double Schiff-base ligands: easy
access to mononuclear precursor and unsymmetric
dinuclear complexes†
Cite this: RSC Adv., 2016, 6, 75844
*
Markus Schmidt, Helmar Gorls and Winfried Plass
¨
A straightforward and easy to handle two-step synthetic route for unsymmetric double Schiff-base ligands
is presented. The isolated intermediate single Schiff-base precursor ligands H2sc-difo and H2tsc-difo were
derived by condensation of 2,6-diformyl-4-methylphenol with semicarbazide and thiosemicarbazide,
respectively. Further reaction of the precursor ligands with different amine components, including both
aliphatic and aromatic examples, allows the synthesis of ditopic unsymmetric double Schiff-base ligands
in high yields and purity. As aliphatic cases we used (2-aminoethyl)bis(2-pyridylmethyl)-amine (H2sc-
hydra and H2tsc-hydra) and 2-(aminomethyl)-pyridine (H2sc-ampy and H2tsc-ampy), whereas 2-
aminophenol was used as an aromatic sample (H3sc-amph and H3tsc-amph). The overall synthetic route
allows for the preparation of the employed ligands in large scale. To explore the coordination capabilities
of the reported ligand systems a mononuclear nickel(II) complex [Ni(tsc-difo)PPh3] and a homodinuclear
zinc(II) complex [Zn2(tsc-hydra)(OAc)2] were synthesized with the single Schiff-base precursor ligand
H2tsc-difo and the double Schiff-base ligands H2tsc-hydra, respectively. Both complexes crystallized in
the monoclinic space group P21/n. For [Ni(tsc-difo)PPh3] a square-planar geometry is found for nickel(II)
ion with H2tsc-difo acting as
a tridentate ligand. Whereas the structure of complex [Zn2(tsc-
Received 30th June 2016
Accepted 2nd August 2016
hydra)(OAc)2] reveals two zinc(II) ions in distinctly different coordination geometry, one in distorted
octahedral coordination located in the bispyridine based binding pocket with [N4O2] donor set and the
other zinc(II) ion in a distorted square-pyramidal coordination given by the thiosemicarbazone based
binding pocket with [NO3S] donor set.
DOI: 10.1039/c6ra16870a
www.rsc.org/advances
in purple acid phosphatases9 (Fe/Zn), copper–zinc superoxide
dismutase10 (Cu/Zn), and arylamine oxygenase AurF11,12 (Fe/
Introduction
Mn). Moreover, bimetallic complexes also play an important
role in catalytic processes and novel abiotic molecule trans-
formations. The concept of cooperative reactivity based on
bimetallic catalysts13–15 has lead to interesting applications such
as asymmetric rearrangements,16 ring opening reactions,17
hydroalkoxylation of alkynes,18 palladium-assisted C–X bond
formation19 and polymerizations.20,21
Over the past decades compartmental ligands capable of
coordinating multiple metal ions have been an intense area of
research.22,23 Among these supporting scaffolds unsymmetric
ligands deliberately providing unequal binding pockets for
metal ions are of particular interest.24–29 Several approaches
have been proposed to synthesize such unsymmetric ligands
that utilize multi-step synthetic routes typically starting from
predesigned unsymmetric bridging units.30–44 Although Schiff-
base ligands have been found to offer excellent potential as
their coordination ability and applications of related complexes
are concerned, their utilization in the design of unsymmetric
ditopic ligand systems is still limited.45,46
Bimetallic active sites are widely spread in metalloenzymes of
numerous biological systems for which examples have been
isolated and structurally characterized.1,2 As a prominent
feature for such active sites the metal centers are usually
embedded in distinctly different binding pockets.3 The result-
ing lack of symmetry can be due to different donor atoms
involved as well as the coordination number and geometry at
the metal sites.4 This enables the two metal centers to perform
different tasks within the enzymatic activity. Examples of such
metalloenzymes range from homodinuclear cases like urease5,6
(Ni2), metallo-b-lactamase7 (Zn2), and the dioxygen carrier
hemerythrin8 (Fe2) towards heterobimetallic metallobiosites as
¨
¨
Institut fur Anorganische und Analytische Chemie, Friedrich-Schiller-Universitat Jena,
Humboldtstrasse 8, 07743 Jena, Germany. E-mail: sekr.plass@uni-jena.de; Fax: +49
3641 948132; Tel: +49 3641 948130
† Electronic supplementary information (ESI) available. CCDC numbers 1043774
([Zn2(tsc-hydra)(OAc)2]) and 1048856 ([Ni(tsc-difo)PPh3]). For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c6ra16870a
75844 | RSC Adv., 2016, 6, 75844–75854
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
Varian 5000 UV/Vis/NIR spectrometer. Mass spectra were
carried out with the help of a MAT95XL Finnigan instrument.
The elemental analyses were determined with a VARIO EL III
and LECO CHN/932 elemental analyzers.
Materials
The starting materials 2,6-diformylcresol (dfc)54 and (2-amino-
ethyl)bis(2-pyridylmethyl)amine55 were prepared according to
the methods described in literature. All other chemicals were
purchased from commercial suppliers and applied as received,
except for the solvents which were puried and distilled prior to
use.
Synthesis of proligands
[(3-Formyl-2-hydroxy-5-methylphenyl)methylidene]aminothi-
ourea (H2tsc-difo). 2,6-Diformylcresol (dfc, 6.2 g, 37.8 mmol)
was dissolved in acetonitrile (100 mL) and placed in a single-
neck round-bottom ask. Subsequently a fritted glass lter
with pressure equalizer was lled with thiosemicarbazide (tsc,
2.24 g, 24.6 mmol) and mounted on the round-bottom ask. A
reux condenser was placed on top of this assembly and linked
to a membrane pump equipped with a pressure control unit
(see Fig. S1†). The pressure in the system was automatically
maintained at about 240 mbar and the reaction solution heated
under reux (at about 40 ꢀC). The reaction mixture turned
immediately yellow and aer a few minutes a yellow precipitate
started to form. The reaction is nished when all tsc was eluted
from the fritted glass. The proligand was separated from the
reaction mixture by ltration, washed a few times with
dichloromethane and dried in vacuo at 45 ꢀC. Yield: 5.43 g
(93%). Anal. calcd for C10H11N3O2S (M ¼ 237.28): C, 50.6; H, 4.7;
Fig. 1 General scheme for the synthesis of unsymmetric double Schiff
bases indicating the possible formation of symmetric side products.
In this context we have reported a versatile synthetic
approach towards double Schiff-base ligands which is based on
stepwise Schiff-base condensation utilizing the symmetric
dicarbonyl bridge 2,6-diformyl-4-methylphenol (dfc) and two
different primary amines (see Fig. 1).47 The related end-off
compartmental ligands systems can be utilized for directed
synthesis of heterobimetallic complexes.48 However, the crucial
step in the synthesis of these double Schiff-base ligands is the
separation of the monocarbonyl precursor ligand from the
symmetric side products by size-exclusion chromatography
which has some drawbacks. Primarily this considerably limits
the scale of reaction to the lower millimolar range and due to
the prolonged times needed during reaction and separation this
can lead to a small portion of undesired re-symmetrization due
to imine metathesis.49
Here we describe a straightforward and easy to handle large
scale synthetic approach towards unsymmetric double Schiff
bases via isolated intermediate single Schiff-base precursors
based on thiosemicarbazide and semicarbazide as amine
components. Schiff bases containing the latter are not only
known for their good coordination abilities50 but also for the
formation of complexes with antibacterial, antiviral, anticancer,
and other biological properties.51–53
1
N, 17.7; S, 13.5%. Found: C, 50.7; H, 4.6; N, 17.9; S, 13.4%. H
NMR (400 MHz, DMSO-d6, d in ppm, see Fig. S2†): 2.30 (s, 3H,
CH3, H-9), 7.58 (s, 1H, H-6), 8.08 (s, 1H, NH2), 8.19 (s, 1H, H-4),
8.24 (s, 1H, NH2), 8.35 (s, 1H, HC]N, H-2), 10.03 (s, 1H, HC]O,
H-10), 10.91 (s, 1H, OH), 11.51 (s, 1H, NH). 13C{1H} NMR (100
MHz, DMSO-d6, d in ppm, see Fig. S2†): 19.7 (C9), 121.8 (C7),
122.1 (C3), 129.1 (C5), 134.2 (C4), 134.3 (C6), 137.1 (C2), 156.7
(C8), 177.9 (C1), 195.7 (C10). MS (DEI, m/z, rel. int. in %): 237
(70, M+), 162 (100), 133 (32), 106 (30), 76 (52). FT-IR: see Fig. S3.†
[(3-Formyl-2-hydroxy-5-methylphenyl)methylidene]aminourea
(H2sc-difo). For the synthesis of H2sc-difo the same experimental
setup as for H2tsc-difo was applied. 2,6-Diformylcresol (dfc, 6.0 g,
36.6 mmol) was dissolved in dichloromethane (100 mL). To this
solution was added triethylamine (6.0 g, 59.3 mmol) and the
solution turned immediately dark red. The semicarbazide
hydrochloride (3.0 g, 26.9 mmol) was placed on the fritted glass
lter which was mounted on the round-bottom ask. The reac-
tion mixture was heated to reux and kept at this temperature
throughout. During the reaction a yellowish precipitate was
formed. Aer all solid starting material was eluted from the
fritted glass lter the reaction mixture was cooled to room
Experimental
Instrumentation
The NMR spectra were measured with Bruker Avance 400 MHz temperature. The precipitate was ltered off, washed several
and 600 MHz spectrometers. For recording the IR spectra times dichloromethane and subsequently dried in vacuo under
a Bruker IFS55/Equinox spectrometer equipped with a diamond reduced pressure. Yield: 4.47 g (74%). Anal. calcd for C10H11N3O3
ATR unit was used. The UV/Vis data were collected on a Cary (M ¼ 221.21): C, 54.3; H, 5.0; N, 19.0%. Found: C, 54.0; H, 5.1; N,
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 75844–75854 | 75845

View Article Online
RSC Advances
Paper
19.2%. 1H NMR (400 MHz, DMSO-d6, d in ppm, see Fig. S4†): 2.29 156.8 (C1), 158.8 (C8), 159.1 (C14/C20), 166.5 (C10). MS
(s, 3H, CH3, H-9), 6.52 (s, 2H, NH2), 7.52 (s, 1H, H-6), 7.99 (s, 1H, (Micro-ESI pos., m/z, rel. int. in %): 468 (100, [M + Na]+). FT-IR:
H-4), 8.13 (s, 1H, HC]N, H-2), 10.09 (s, 1H, HC]O, H-10), 10.38 see Fig. S9.†
(s, 1H, NH), 11.13 (s, 1H, OH). 13C{1H} NMR (100 MHz, DMSO-d6,
[(2-Hydroxy-3-[(pyridin-2ylmethyl)imino]methylphenyl)methy-
d in ppm, see Fig. S4†): 19.7 (C9), 121.9 (C7), 122.2 (C3), 128.8 lidene]aminothiourea (H2tsc-ampy). 2-(Aminomethyl)-pyridine:
(C5), 132.3 (C6), 134.1 (C4), 135.5 (C2), 156.3 (C1), 156.4 (C8), 456 mg, 4.21 mmol; proligand H2tsc-difo: 1.00 g, 4.21 mmol.
194.6 (C10). MS (DEI, m/z, rel. int. in %): 237 (98, M+), 193 (67), Yield: 1.190 g (86%). Anal. calcd for C16H17N5OS (M ¼ 327.40):
162 (100), 133 (82), 106 (57). FT-IR: see Fig. S5.†
C, 58.7; H, 5.2; N, 21.4; S, 9.8%. Found: C, 58.4; H, 5.2; N, 21.1; S,
9.5%. 1H NMR (400 MHz, DMSO-d6, d in ppm, for see Fig. S10†):
2.26 (s, 3H, H-9), 4.91 (s, 2H, H-11), 7.31 (m, 2H, H-6/H-15), 7.41
(d, J ¼ 7.9 Hz, 1H, H-13), 7.81 (m, 1H, H-14), 7.99 (s, 1H, NH2),
Synthesis of double Schiff bases
A
solution of (2-aminoethyl)bis(2-pyridylmethyl)amine in 8.04 (m, 1H, H-4), 8.17 (s, 1H, NH2), 8.39 (s, 1H, H-2), 8.55 (m,
methanol (400 mL) was added dropwise over a period of 24 h to 1H, H-16), 8.69 (s, 1H, H-10), 11.46 (s, 1H, NH), 14.18 (s, 1H,
a yellow suspension of one equivalent of the corresponding OH). 13C{1H} NMR (100 MHz, DMSO-d6, d in ppm, see
proligand in methanol (100 mL). The reaction mixture imme- Fig. S10†): 19.9 (C9), 63.0 (C11), 118.5 (C7), 121.5 (C3), 122.2
diately turned to an orange to red color and became a clear (C13), 122.6 (C15), 126.9 (C5), 129.4 (C4), 133.9 (C6), 137.1 (C14),
solution at the end of the addition. Subsequently the solvent 137.3 (C2), 149.3 (C16), 157.5 (C12), 158.6 (C8), 167.5 (C10),
was removed under reduced pressure at a temperature of 40 ꢀC 177.8 (C1). MS (Micro-ESI pos., m/z, rel. int. in %): 350 (100, [M +
by means of a rotary evaporator. The residual orange-red solid Na]+). FT-IR: see Fig. S11.†
was washed several times with diethyl ether to afford the
unsymmetric double Schiff-base ligand as orange to red lidene]aminourea (H2sc-ampy). 2-(Aminomethyl)-pyridine: 586
powder. mg, 5.42 mmol; proligand H2sc-difo: 1.20 g, 5.42 mmol. Yield:
[(2-Hydroxy-3-[(pyridin-2ylmethyl)imino]methylphenyl)methy-
[(3-[(2-[Bis(pyridin-2-ylmethyl)amino]ethylimino)methyl]-2- 1.60 g (95%). Anal. calcd for C16H17N5O2 (M ¼ 311.34): C, 61.7;
1
hydroxy-5-methylphenylmethylidene)amino]thiourea (H2tsc- H, 5.5; N, 22.5%. Found: C, 61.4; H, 5.55; N, 22.7%. H NMR
hydra). (2-Aminoethyl)bis(2-pyridylmethyl)amine: 2.79 g, 11.5 (400 MHz, DMSO-d6, d in ppm, see Fig. S12†): 2.26 (s, 3H, H-9),
mmol; proligand H2tsc-difo: 2.73 g, 11.5 mmol. Yield: 4.70 g 4.90 (s, 2H, H-11), 6.48 (s, 2H, NH2), 7.27 (m, 1H, H-6), 7.31 (m,
(88%). Anal. calcd for C24H27N7OS (M ¼ 461.59): C, 62.4; H, 5.9; 1H, H-15), 7.40 (d, J ¼ 8.0 Hz, 1H, H-13), 7.85 (m, 1H, H-14), 7.92
1
N, 21.2; S, 6.95%. Found: C, 62.1; H, 5.9; N, 21.1; S, 6.9%. H (m, 1H, H-4), 8.17 (s, 1H, H-2), 8.55 (m, 1H, H-16), 8.69 (s, 1H, H-
NMR (400 MHz, DMSO-d6, d in ppm, see Fig. S6†): 2.26 (s, 3H, H- 10), 10.62 (s, 1H, NH), 14.02 (s, 1H, OH). 13C{1H} NMR (150
9), 2.80 (t, J ¼ 5.5 Hz, 2H, H-12), 3.76 (t, J ¼ 5.5 Hz, 2H, H-11), MHz, DMSO-d6, d in ppm, see Fig. S12†): 19.9 (C9), 63.2 (C11),
3.82 (s, 4H, H-13/H-19), 7.22 (m, 3H, H-6 and H-17/H-23), 7.46 118.5 (C7), 121.0 (C3), 122.1 (C13), 122.6 (C15), 127.0 (C5), 129.0
(d, J ¼ 8.0 Hz, 2H, H-15/H-21), 7.65 (ddd, J ¼ 8.0, 8.0, 1.6 Hz, 2H, (C4), 132.9 (C6), 134.2 (C2), 137.1 (C14), 149.3 (C16), 156.8 (C1),
H-16/H-22), 8.02 (s, 1H, NH2), 8.04 (m, 1H, H-4), 8.18 (s, 1H, 157.4 (C12), 157.6 (C8), 167.5 (C10). MS (Micro-ESI pos., m/z, rel.
NH2), 8.47 (m, 4H, H-10/H-2 and H-18/H-24), 11.48 (s, 1H, NH), int. in %): 334 (100, [M + Na]+). FT-IR: see Fig. S13.†
14.37 (s, 1H, OH). 13C{1H} NMR (100 MHz, DMSO-d6, d in ppm,
[(2-Hydroxy-3-[N-(2-hydroxyphenyl)carboximidoyl]-5-methyl-
see Fig. S6†): 19.9 (C9), 53.8 (C12), 54.4 (C11), 59.6 (C13/C19), phenylmethylidene)amino]thiourea (H3tsc-amph). 2-Amino-
118.0 (C7), 121.9 (C3), 122.1 (C17/C23), 122.5 (C15/C21), 125.9 phenol: 460 mg, 4.21 mmol; proligand H2tsc-difo: 1.00 g, 4.21
(C5), 129.7 (C4), 133.7 (C6), 136.4 (C16/C22), 137.8 (C2), 148.7 mmol. Yield: 1.118 g (81%). Anal. calcd for C16H16N4O2-
(C18/C24), 159.1 (C14/C20), 160.5 (C8), 166.5 (C10), 177.7 (C1). S$0.5MeOH (M ¼ 344.41): C, 57.5; H, 5.3; N, 16.3; S, 9.3%.
1
MS (Micro-ESI neg., m/z, rel. int. in %): 460 (100, [M ꢁ Hꢁ), 293 Found: C, 57.35; H, 5.0; N, 16.6; S, 9.6%. H NMR (400 MHz,
(37), 255 (20). FT-IR: see Fig. S7.†
DMSO-d6, d in ppm, for see Fig. S14†): 2.29 (s, 3H, H-9), 6.88 (dd,
[(3-[(2-[Bis(pyridin-2-ylmethyl)amino]ethylimino)methyl]-2- J ¼ 8.2 Hz, 1H, H-13), 6.97 (d, J ¼ 8.2 Hz, 1H, H-15), 7.13 (dd, J ¼
hydroxy-5-methylphenylmethylidene)amino]urea (H2sc-hydra). 8.2 Hz, 1H, H-14), 7.39 (d, J ¼ 8.2 Hz, 1H, H-12), 7.42 (m, 1H, H-
(2-Aminoethyl)bis(2-pyridylmethyl)amine: 1.41 g, 5.8 mmol; 6), 8.00 (s, 1H, NH2), 8.08 (m, 1H, H-4), 8.17 (s, 1H, NH2), 8.46 (s,
proligand H2sc-difo: 1.29 g, 5.8 mmol. Yield: 2.32 g (86%). Anal. 1H, H-2), 8.95 (s, 1H, H-10), 9.85 (s, 1H, O2H), 11.48 (s, 1H, NH),
calcd for C24H27N7O2$0.5MeOH (M ¼ 461.54): C, 63.8; H, 6.3; N, 14.62 (s, 1H, O1H). 13C{1H} NMR (100 MHz, DMSO-d6, d in ppm,
1
21.2%. Found: C, 63.5; H, 6.3; N, 21.15%. H NMR (400 MHz, see Fig. S14†): 20.0 (C9), 117.0 (C15), 119.3 (C7), 119.5 (C12),
DMSO-d6, d in ppm, see Fig. S8†): 2.25 (s, 3H, H-9), 2.79 (t, J ¼ 119.7 (C13), 121.6 (C3), 127.1 (C5), 128.4 (C14), 129.8 (C4), 134.0
5.8 Hz, 2H, H-12), 3.74 (t, J ¼ 5.8 Hz, 2H, H-11), 3.81 (s, 4H, H-13/ (C11), 134.3 (C6), 137.4 (C2), 151.2 (C16), 158.6 (C8), 161.3 (C10),
H-19), 6.50 (s, 2H, NH2), 7.15 (m, 1H, H-6), 7.20 (m, 2H, H-17/H- 177.8 (C1). MS (Micro-ESI pos., m/z, rel. int. in %): 351 (100, [M +
23), 7.44 (d, J ¼ 8.1 Hz, 2H, H-15/H-21), 7.63 (ddd, J ¼ 8.1, 8.1, Na]+). FT-IR: see Fig. S15.†
1.6 Hz, 2H, H-16/H-22), 7.91 (m, 1H, H-4), 8.20 (s, 1H, H-2), 8.45
[(2-Hydroxy-3-[N-(2-hydroxyphenyl)carboximidoyl]-5-methyl-
(m, 3H, H-10 and H-18/H-24), 10.28 (s, 1H, NH), 14.17 (s, 1H, phenylmethylidene)amino]urea (H3sc-amph). 2-Aminophenol:
OH). 13C{1H} NMR (100 MHz, DMSO-d6, d in ppm, see Fig. S8†): 74 mg, 0.68 mmol; proligand H2sc-difo: 150 mg, 0.68 mmol.
20.0 (C9), 53.9 (C12), 54.9 (C11), 59.6 (C13/C19), 118.2 (C7), Yield: 200 g (91%). Anal. calcd for C16H16N4O3$0.5MeOH (M ¼
122.1 (C17/C23), 122.3 (C3), 123.0 (C15/C21), 126.2 (C5), 128.9 328.35): C, 60.4; H, 5.5; N, 17.1%. Found: C, 60.5; H, 5.4; N,
1
(C4), 132.7 (C6), 134.6 (C2), 136.4 (C16/C22), 148.7 (C18/C24), 17.1%. H NMR (600 MHz, DMSO-d6, d in ppm, see Fig. S16†):
75846 | RSC Adv., 2016, 6, 75844–75854
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
2.29 (s, 3H, H-9), 6.50 (s, 2H, NH2), 6.88 (dd, J ¼ 8.2 Hz, 1H, H- 7.96 (dd, J ¼ 80 Hz, 2H, H-16/H-22), 8.10 (s, 1H, H-2), 8.40 (s,
13), 6.98 (d, J ¼ 8.2 Hz, 1H, H-15), 7.13 (dd, J ¼ 8.2 Hz, 1H, H-14), 1H, H-10), 8.53 (s(br), 2H, H-18/H-24). 13C{1H} NMR (150 MHz,
7.37 (m, 1H, H-12), 7.38 (m, 1H, H-6), 7.96 (m, 1H, H-4), 8.25 (s, DMSO-d6, d in ppm, see Fig. S21†): 19.2 (C9), 24.0 (C26/C28),
1H, H-2), 8.93 (s, 1H, H-10), 9.84 (s, 1H, O2H), 10.29 (s, 1H, NH), 54.3 (C11), 57.4 (C12), 60.5 (C13/C19), 120.7 (C7), 123.2 (C5),
14.48 (s, 1H, O1H). 13C{1H} NMR (150 MHz, DMSO-d6, d in ppm, 123.5 (C3/C15/C21), 124.0 (C17/C23), 137.9 (C6), 138.8 (C4),
see Fig. S16†): 20.0 (C9), 116.6 (C15), 119.3 (C7), 119.5 (C12), 139.4 (C16/C22), 147.6 (C18/C24), 151.0 (C2), 155.5 (C14/C20),
119.6 (C13), 122.1 (C3), 127.1 (C5), 128.3 (C14), 129.3 (C4), 133.4 165.4 (C8), 168.0 (C10), 174.1 (C25/C27), 174.1 (C1). MS
(C6), 134.2 (C11), 134.4 (C2), 151.2 (C16), 156.8 (C1), 157.6 (C8), (Micro-ESI pos., m/z, rel. int. in %, see Fig. S22†): 648 (100, [M ꢁ
161.4 (C10). MS (Micro-ESI pos., m/z, rel. int. in %): 335 (100, [M OAc]+), 608 (67, [M ꢁ 2OAc + OH]+), 588 (57), 490 (22), 448 (41).
+ Na]+). FT-IR: see Fig. S17.†
FT-IR: see Fig. S23.†
X-ray crystallographic studies
Synthesis of complexes
The intensity data were collected on a Nonius KappaCCD
diffractometer, using graphite-monochromated Mo-Ka radia-
[Ni(tsc-difo)PPh3]. Triphenylphosphane (113 mg, 0.43 mmol)
and the proligand H2tsc-difo (100 mg, 0.42 mmol) were sus-
pended in methanol (5 mL). Triethylamine (86 mg, 0.85 mmol)
was added to this slurry. This led to a color change from yellow
to orange. Subsequently a solution of nickel(II) perchlorate
hexahydrate (154.3 mg, 0.42 mmol) in methanol (5 mL) was
added dropwise to the orange reaction mixture under stirring.
The mixture was continuously stirred until a clear red solution
was formed. The nal reaction solution was ltered and the
resulting ltrate was allowed to stand at room temperature.
Aer one day reddish crystals of [Ni(tsc-difo)PPh3] precipitated
and were collected by ltration. The crystalline material was
dried in vacuo for 20 h. Yield: 130 mg (53%). Anal. calcd for
˚
tion (l ¼ 0.71073 A). Data were corrected for Lorentz and
polarization effects. Absorption was taken into account on
a semi-empirical basis using multiple-scans.56–58 The structures
were solved by direct methods (SHELXS)59 and rened by full-
2
matrix least squares techniques against Fo (SHELXL-97).59 In
the crystal structure of [Zn2(tsc-hydra)(OAc)2]$MeCN$H2O one
of the pyridyl groups was found to be slightly disordered on two
positions (ratio of site occupation factors is about 6 to 1). The
hydrogen atoms of the amine group (N1) and the water mole-
cule (O1W) in the crystal structure of the zinc complex were
located by difference Fourier synthesis and rened isotropically.
All other hydrogen atom positions were included at calculated
positions with xed thermal parameters. All non-hydrogen and
non-disordered atoms were rened using anisotropic thermal
parameters. Crystallographic data as well as structure solution
and renement details for [Ni(tsc-difo)PPh3]$2MeOH and
C
28H24N3NiO2PS$0.7MeOH (M ¼ 578.67): C, 59.6; H, 4.7; N, 7.3;
1
S, 5.5%. Found: C, 59.5; H, 4.6; N, 7.2; S, 5.4%. H NMR (400
MHz, CD2Cl2, d in ppm, see Fig. S18†): 2.23 (s, 3H, H-9), 4.79 (s,
4
2H, NH2), 7.33 (d, J ¼ 2.4 Hz, 1H, H-4), 7.43 (m, 7H, H-6 and
PPh3), 7.52 (m, 3H, PPh3), 7.80 (m, 6H, PPh3), 8.21 (d, 4JPH ¼ 8.9
Hz, 1H, H-2), 8.90 (s, 1H, H-10). 13C{1H} NMR (100 MHz, CD2Cl2,
d in ppm, see Fig. S18†): 20.1 (C9), 121.3 (C7), 124.6 (C5), 126.2
(C3), 129.0 (d, 3JPC ¼ 10.3 Hz), 129.4 (d, 1JPC ¼ 46.9 Hz), 131.5 (d,
[Zn2(tsc-hydra)(OAc)2]$MeCN$H2O
Table S1.†
are
summarized
in
2
4JPC ¼ 2.1 Hz), 132.1 (C6), 134.7 (d, JPC ¼ 10.5 Hz), 139.7 (C4),
Results and discussion
Mono Schiff-base proligands
151.7 (C2), 161.6 (C8), 172.3 (d, 3JPC ¼ 16.8 Hz, C1), 191.2 (C10).
31P{1H} NMR (162 MHz, CD2Cl2, d in ppm): 20.63. UV/Vis
(CH2Cl2, lmax in nm, 3 in Mꢁ1 cmꢁ1, see Fig. S19†): 571 (112,
shoulder), 445 (10 155), 427 (8770, shoulder), 386 (10 349), 370
(8458, shoulder), 340 (5907), 303 (18 189). MS (Micro-ESI pos.,
m/z, rel. int. in %): 577.8 (66, [M + Na]+), 413 (26), 333 (58), 301
(100), 263 (62, P(Ph)3). FT-IR: see Fig. S20.†
First attempts to synthesize the desired mono Schiff-base pro-
ligand H2tsc-difo depicted in Fig. 2 utilized the slow addition of
a diluted thiosemicarbazide (tsc) solution to a concentrated
solution of dfc in methanol over a period of one week. Although
this successfully led to the formation of the desired mono Schiff
base, the product contained a considerable amount of the
symmetric double Schiff base as byproduct. Since the resulting
product mixture was only sparingly soluble in acetonitrile and
chloroform, standard recrystallization could not be applied.
[Zn2(tsc-hydra)(OAc)2]. To a suspension of H2tsc-hydra (241
mg, 0.52 mmol) in acetonitrile (10 mL) was added a solution of
triethylamine (107 mg, 1.06 mmol) in acetonitrile (2 mL).
Subsequently a solution of zinc(II) acetate dihydrate (228 mg,
1.04 mmol) in acetonitrile/methanol (5 mL/5 mL) was added
dropwise to the reaction mixture. A clear orange solution was
formed. Slow evaporation of the solvent in air gave yellow
crystals which were dried in air. Yield: 100 mg (25%). Anal. calcd
for C28H31N7O5SZn2$2H2O (M ¼ 744.45): C, 45.2; H, 4.7; N, 13.2;
1
S, 4.3%. Found: C, 44.9; H, 4.4; N, 13.2; S, 4.2%. H NMR (400
MHz, DMSO-d6, d in ppm, see Fig. S21†): 1.65 (s, 6H, OAcꢁ), 2.19
(s, 3H, H-9), 2.82 (s(br), 2H, H-12), 2.98 (m, 2H, H-11), 4.34 (d, J
¼ 15.7 Hz, 2H, Ha-13/Ha19), 4.62 (d, J ¼ 15.7 Hz, 2H, Hb-13/
Hb19), 6.22 (s, 2H, NH2), 7.02 (m, 1H, H-6), 7.30 (m, 1H, H-4),
7.43 (m, 2H, H-17/H-23), 7.51 (d, J ¼ 8.0 Hz, 2H, H-15/H-21), Fig. 2 Mono Schiff-base proligands.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 75844–75854 | 75847

View Article Online
RSC Advances
Paper
However, attempts by Soxhlet extraction with chloroform over possesses a somewhat better solubility and is therefore
a period of four days could successfully be utilized to separate partially lost during the washing process.
the unsymmetric proligand from the undesired symmetric side
Both proligands H2sc-difo and H2tsc-difo can be obtained in
product. H2tsc-difo was extracted from the crude reaction high yields as pure solid materials. This synthetic route
product and precipitated in pure form as a yellow solid which is provides a large scale access to these versatile ligand systems
evident by comparison of the NMR spectra before and aer which can be utilized for further derivatization in various ways.
extraction (Fig. S24†). Based on these observations we supposed The available free carbonyl group of the proligands can be
that under conditions of continuous dilution over the whole functionalized with other amine components to yield the
period of reaction, with respect to the amine component tsc, it desired unsymmetric double Schiff bases. Alternatively the
should be possible to generate solely H2tsc-difo without any proligands can directly used for coordination of metal ions
symmetric byproduct.
leading to mononuclear complexes which in turn could be
Along this line it turned out to be benecial that dfc shows further functionalized at the remaining carbonyl group.
a solubility in acetonitrile which is by far larger than that of tsc.
This allows during the reaction to simultaneously maintain
a rather high dfc concentration paired with a situation of
Double Schiff bases
continuous dilution with respect to tsc. The desired idealized
reaction conditions should combine a steady but very small
intake of tsc to a highly concentrated dfc reaction solution.
These conditions, best described as slow solution transport, can
be achieved by a simple reaction setup which utilizes the solvent
extraction of tsc from a fritted glass lter by acetonitrile under
reux conditions as depicted in Fig. S1.† To maintain the
desired dilution conditions with respect to the amine compo-
nent throughout the whole reaction time a 1.5 stoichiometric
excess of the carbonyl component dfc was used. Within a period
of a about two days the complete amount of tsc was eluted into
the reaction mixture and the proligand H2tsc-difo was formed
as yellow solid precipitate insoluble in the reaction mixture. As
the solubility of the mono Schiff-base proligand increases with
temperature, which would favor the formation of the undesired
symmetric byproduct, the reaction temperature was kept below
approximately 40 ꢀC by reducing the pressure in the reaction
vessel and thereby lowering the boiling point of the reaction
solvent acetonitrile. The remaining excess of dfc can easily be
recovered from the nal solid reaction product by washing the
yellow powder several times with either chloroform or
dichloromethane. The scale-up of this procedure was optimized
to produce the proligand in gram scale and over 90% yield. The
basic limiting factor is the solubility of the dfc starting material
in the given reaction volume.
Starting from the proligands H2sc-difo and H2tsc-difo unsym-
metric double Schiff bases can be derived by condensation in
methanol with the appropriate amine components. To probe
the synthetic versatility of this approach we utilized three
different primary amines including aliphatic and aromatic
examples which vary the number and nature of the introduced
donor atoms, namely (2-aminoethyl)bis(2-pyridylmethyl)amine,
2-(aminomethyl)-pyridine and 2-aminophenol. These reactions
were performed under heterogeneous conditions since the
proligands were only sparingly soluble in methanol. The
resulting double Schiff bases depicted in Fig. 3 are obtained in
high yield and purity without any indication of imine metath-
esis during the course of reactions.
This synthetic strategy should be transferable to the reaction
of dfc with semicarbazide (sc). However, the varied solubility
properties of semicarbazide and the fact that it is commercially
available as hydrochloride, require some modications of the
applied procedure. In this case it was necessary to utilize
dichloromethane as reaction solvent, since the solubility of
semicarbazide hydrochloride is too high in acetonitrile to
prevent the formation of the undesired symmetric side product.
Moreover, to generate the free semicarbazide triethylamine was
added as base to the reaction mixture. As in the previous case
the semicarbazide is slowly eluted into the reaction ask. The
product H2sc-difo (see Fig. 2) is formed as a pale yellow
precipitate which can be isolated from the crude reaction
mixture by ltration and subsequent washing with dichloro-
methane. However, the yield is slightly lower compared to the
previous case of the thiosemicarbazone derivative as H2sc-difo
Fig. 3 Synthesized double Schiff-base ligands based on the proligands
H2sc-difo and H2tsc-difo.
75848 | RSC Adv., 2016, 6, 75844–75854
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
All these potential ligands contain two distinct binding
RSC Advances
pockets for the coordination of metal ions. According the nature
of the second amine group introduced these ligands fall into
two groups with either an additional exible or rigid donor
fragment, besides the generally present semicarbazone or thi-
osemicarbazone moiety which provides a binding pocket with
rigid tridentate donor set.
Fig. 5 Mesomeric forms for the thiosemicarbazone based ligands
H2tsc-difo, H2tsc-hydra, H2tsc-ampy and H3tsc-amph preventing free
rotation of the NH2 group.
Selected 1H NMR data for the double Schiff bases are
summarized in Table 1. The resonances of the methine protons
assigned to the imine groups are observed in the usual range
and show the expected shielding effect when compared to the
corresponding resonance of the proligands (H-10). These data
further indicate the presence of strong hydrogen-bonding
interaction between the hydroxy group of the bridging
aromatic moiety and the adjacent imino group as depicted in
Fig. 4. This leads to a resonance-assisted hydrogen bond
N–H/O which is well known for Schiff bases containing sali-
cylidene moieties.60,61 As a consequence the corresponding
proton resonance is considerably shied downeld to values of
more than 14 ppm in comparison to the resonances observed
for the proligands H2sc-difo and H2tsc-difo at around 11 ppm
lacking this interaction. A comparison of selected 13C NMR data
for the proligands and double Schiff bases are summarized in
Table S2.†
thiosemicarbazones this is known to lead to restricted rotation
of the NH2 group,63,64 which might be attributed to an increased
contribution of the zwitterionic resonance form (see Fig. 5) as
well as the possible hydrogen bonding of one of the NH2
protons with the azomethine nitrogen atom. This is obvious
from two independent resonances for the NH2 protons within
the thiosemicarbazone series which are both shied downeld
with respect to the corresponding semicarbazones.
For the double Schiff base H2tsc-hydra this effect has been
1
more closely examined by variable temperature H NMR spec-
troscopy with the resulting spectra depicted in Fig. 6. The two
resonances observed for the NH2 group at room temperature
coalesce upon increasing the temperature. From the spectral
data the free energy of activation DG‡ can be estimated65 to 69.9
kJ molꢁ1 which is in good agreement with reported values.66
The observed NMR data is consistent with a preserved
solution behavior for the semicarbazone and thio-
semicarbazone moieties within the two series of mono and
double Schiff bases. A usually observed structural feature for
these class of compounds is the almost planar C]N–NH–CX–
NH2 backbone with a trans arrangement of the azomethine and
Ni(II) complex with the proligand H2tsc-difo
The mononuclear complex [Ni(tsc-difo)PPh3] was synthesized
by slow addition of a methanol solution of nickel(II) perchlorate
hexahydrate to a slurry of the mono Schiff-base proligand H2tsc-
difo containing one equivalent of triphenylphosphane as
potential coligand and two equivalents of triethylamine as base.
Upon complexation of the nickel ions a color change from
yellow to dark red is observed and the reaction mixture turns in
a clear red solution. The observed color indicates a square-
planar coordination geometry at the nickel(II) ion, as expected
for a coordination of the strong phosphane ligand. This is
the
X
(O, S) atom as depicted in Fig. 5.62 For the
1
Table 1 Selected H NMR data for mono and double Schiff bases (d/
ppm)
Ligand
N–H/O
OH
H-10
H-2
NH
NH2
H2sc-difo
H2tsc-difo
—
—
11.13
10.91
10.09
10.03
8.13
8.35
10.38
11.51
6.52
8.08
8.24
6.50
8.02
8.18
6.48
7.99
8.17
6.50
8.00
8.17
H2sc-hydra
H2tsc-hydra
14.17
14.37
—
—
8.45
8.47
8.20
8.47
10.28
11.48
H2sc-ampy
H2tsc-ampy
14.02
14.18
—
—
8.69
8.69
8.17
8.39
10.62
11.46
H3sc-amph
H3tsc-amph
14.48
14.62
9.84
9.85
8.93
8.95
8.25
8.46
10.29
11.48
Fig.
measured at a spectrometer frequency of 400 MHz showing the
Fig. 4 Tautomerization between the hydroxy-imine and keto-amine coalescence for the proton resonances of the NH2 group (marked
6
Variable temperature 1H NMR spectra for H2tsc-hydra
forms of the free double Schiff-base ligands in solution.
peaks).
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 75844–75854 | 75849

View Article Online
RSC Advances
Paper
conrmed by the UV/Vis spectrum of the isolated crystalline
complex which is typical for a square-planar nickel(II) complex67
with thiosemicarbazone ligand featuring additional charge-
transfer bands.64,68–70
The well resolved 1H NMR spectrum of [Ni(tsc-difo)PPh3]
measured for a dichloromethane-d2 solution is consistent with
the expected diamagnetic ground state for a square-planar
conguration at the nickel(II) center. The protons related to
the resonance observed at 4.79 ppm are affected by H–D
exchange and consequently assigned as the NH2 group of the
thiosemicarbazone moiety, which is well within the usually
observed range for anionic thiosemicarbazones coordinated to
metal ions.50 The fact that in contrast to the free ligand only one
resonance is observed for the NH2 group can be attributed to
missing intramolecular hydrogen bonding due to an altered
conguration of the thiosemicarbazone moiety in the complex.
The protons related to the second resonance showing H–D
exchange characteristic observed at 3.42 ppm are assigned to
methanol molecules which are included in the crystal structure.
Based on the integration of the resonance peak this corre-
sponds to a methanol content of about 0.7 equivalents per
complex unit which is in good agreement with the elemental
analysis of the crystalline material dried in vacuo. The reso-
nance of the triphenylphosphane protons are observed in the
usual range,50 with the multiplet at 7.43 ppm being super-
imposed with the resonance of the ring proton H-6 of the 2,6-
diformylcresol moiety. The resonance of the azomethine proton
(H-2) is slightly shied upeld upon coordination to 8.21 ppm
and is split to a doublet due to coupling with the phosphorus
atom of the triphenylphosphane in trans position at the nickel
Fig. 7 Molecular structure of [Ni(tsc-difo)PPh3]. Thermal ellipsoids are
drawn with 50% probability level and hydrogen atoms attached to
carbon are omitted for clarity. Pertinent distances (in pm): Ni–S
212.82(8), Ni–P 219.68(8), Ni–O1 185.8(2), Ni–N3 188.7(2), S–C1
175.2(3), N1–C1 135.6(4), N2–C1 130.5(4), N2–N3 139.9(3), N3–C2
130.3(4).
group (N1) and the aldehyde moiety (O2) of a neighboring
complex molecule leading to the formation of a chain along the
ꢀ
crystallographic [101] direction as depicted in Fig. 8. In addition
NH/p interactions are observed between the second proton of
the NH2 groups of the thiosemicarbazone moiety and the
aromatic ring of an adjacent complex.74,75 This leads to a zig–zag
chain like association along the [010] direction (see Fig. S25†).
Dinuclear Zn(II) complex with H2tsc-hydra
4
ion with a rather large coupling constant JPH ¼ 8.9 Hz.71 The
The complex [Zn2(tsc-hydra)(OAc)2] was obtained from the
reaction of two equivalents of zinc(II) acetate dihydrate and the
double Schiff-base ligand H2tsc-hydra in a mixture of acetoni-
trile and methanol in the presence of triethylamine as base. The
constitution of the complex was conrmed by analytical and
spectroscopic methods. In particular the solution structure was
studied by NMR spectroscopy.
4
observation of a rather large JPH coupling indicates the pres-
ence of a highly rigid structural arrangement of the involved
bonding backbone in solution.72 The 31P NMR resonance for
[Ni(tsc-difo)PPh3] observed at 20.63 ppm is consistent with the
usual range for coordination shis observed for triphenyl-
phosphane coordinated to nickel(II) ions.73
Crystals of [Ni(tsc-difo)PPh3] were obtained by slow evapora-
tion of the solvent from the ltrated reaction mixture and were
found to crystallize in the monoclinic space group P21/n together
with two molecules of methanol. The molecular structure of the
neutral complex is depicted in Fig. 7 (selected bond angle see
Table S3†) and conrms the square-planar geometry at the
nickel(II) center. The almost ideal square-planar coordination
environment is given by the donor atoms O1, N3 and S of the
proligand and P of the triphenylphosphane with a deviation of
the nickel atom from the mean plane by only 2 pm. The bond
lengths at the nickel(II) ion are within the expected range for
similar complexes and consistent with the deprotonated thiolate
form of the thiosemicarbazone fragment expected for a neutral
complex.64,70,71 The bite angles for the ve- and six-membered
chelate rings of the tridentate thiosemicarbazone ligand are
95.1ꢀ (O1–Ni–N3) and 87.3ꢀ (N3–Ni–S1), respectively. The two
planar chelate rings show a dihedral angle of 12ꢀ, which is due to
a slight rotation about the C2–C3 bond.
The 1H NMR spectra indicate signicant changes upon
coordination of the H2tsc-hydra to the zinc(II) ions with the
observed resonances being generally broader than in the case of
the free ligand. As in the case of the [Ni(tsc-difo)PPh3] the thi-
osemicarbazone moiety shows the typical features expected for
the coordinated thiolate form with a singlet at 6.22 ppm for the
protons of the NH2 group. The latter assignment was conrmed
Fig. 8 Hydrogen bonded chains in the crystal structure of [Ni(tsc-difo)
PPh3]$2MeOH along the [1ꢀ01] direction. Pertinent distances (in pm):
The two additional molecules of methanol in the crystal
structure are involved in hydrogen bonding between the NH2 N1/O1M 291.6(5), O1M/O2M 269.8(5), O2/O2M 271.1(4).
75850 | RSC Adv., 2016, 6, 75844–75854
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
by H–D exchange experiments. The two pyridyl rings give rise the overall structure can be expected as being governed by the
to only one set of resonances consistent with the equivalence donor properties and the exibility of the two distinctly
of the two coordinated pyridyl moieties. Similarly for the two different binding pockets ligand system. The overall coordina-
acetate anions present in the complex only a single broad tion of the zinc(II) ions is complemented by two additional
resonance at 1.65 ppm is observed indicating their chemical acetate anions one in a m,h1-bridging mode and the second one
equivalence on the NMR time scale. The resonances for the as a terminal monodentate ligand at zinc center located in the
methylene protons within the ethylenediamine bridge thiosemicarbazone pocket (Zn1).
observed at 2.82 (C12) and 2.98 ppm (C11) show the basic
The central Zn2O2 moiety is virtually planar within a devia-
trends upon coordination usually observed in the litera- tion of less than 2 pm from the mean plane. The two corre-
ture.48,76,77 However, in contrast to the free ligand and to an sponding basal coordination planes at the square-planar Zn1
earlier reported dinuclear zinc complex with a similar ligand center (S, O1, O4, and N3) and the octahedral Zn2 center (O1,
framework spin–spin coupling is not resolved.48 Moreover, O4, N4, and N5) show dihedral angles of 18ꢀ and 7ꢀ with the
the resonance for the methylene group (2.82 ppm) attached to central Zn2O2 moiety, respectively. Interestingly the deviations
the tertiary nitrogen donor appears as a very broad singlet of the zinc ions from the respective mean planes exhibit
with a width at half-height of about 125 Hz. On the other distinct differences (Zn1: 58 pm; Zn2: 3 pm) indicating
hand, for the methylene hydrogens of the pyridyl arms (C13 considerable distortion within the basal coordination plane at
and C19) a well resolved AB pattern with a coupling constant the Zn2 center. This also reects in the deviation of the
of 16.8 Hz is observed.65 This is typical for a geminal coupling nitrogen donor atoms N4 (ꢁ59 pm) and N5 (21 pm) from the
related to this type of coordination pocket and clearly indi- mean plane of the central Zn2O2 moiety. The overall situation
cates the stereochemical disparity of the involved hydrogen is depicted in Fig. 10.
atoms.48,78
To accommodate the rigidity of the p conjugated part of the
Crystals of [Zn2(tsc-hydra)(OAc)2] suitable for single crystal ligand backbone to the described distortion the bridging
analysis were obtained by slow evaporation of the solvent. The phenolate fragment is tilted with respect to the central Zn2O2
neutral complex was found to co-crystallize with one additional moiety. This corresponds to a rotation about the C2–C3 bond
molecule of water and acetonitrile as [Zn2(tsc-hydra)(OAc)2]$ leading to a dihedral angle of around 16ꢀ (see Fig. S26†).
MeCN$H2O in the monoclinic space group P21/n. The molecular Moreover, there is an additional source of distortion for the
structure of the neutral complex is depicted in Fig. 9 (selected pyridyl based binding compartment of the ligand system
bond angle see Table S4†).
around Zn2 which is due to the ve-membered chelate rings
Two different binding modes are observed for the two leading to signicant decrease of the trans angles with respect
coordinated zinc(II) ions. Zn1 is found in a ve-coordinate to an ideal octahedral geometry (O1–Zn2–N5 161.9ꢀ, O4–Zn2–
square-pyramidal environment with an [NO3S] donor set N4 155.6ꢀ, N6–Zn2–N7 149.3ꢀ). As a consequence there is
whereas for Zn2 a six-coordinate octahedral geometry with enough space opposite to the ligand backbone at the two zinc(II)
[N4O2] donor set is observed. This is not surprising, as zinc(II) ions to allow a coplanar orientation of the bridging acetate
ions usually show no specic structural preferences. Therefore anion with respect to the central Zn2O2 moiety.
The supramolecular arrangement within the crystal struc-
ture is governed by hydrogen bonding between pairs of neutral
complexes via the thiosemicarbazone fragment of adjacent
molecules. Together with hydrogen bonding towards the addi-
tional co-crystallized water molecule this leads to the formation
Fig. 9 Molecular structure of [Zn2(tsc-hydra)(OAc)2]. Thermal ellip- Fig. 10 Representation of the coordinations spheres of the zinc(II) ions
soids are drawn with 50% probability level and hydrogen atoms in [Zn2(tsc-hydra)(OAc)2]. The two depicted planes contain the
attached to carbon are omitted for clarity. Pertinent distances (in pm): common O1–O4 axis as hinge and correspond to the mean planes
Zn1–S 235.11(12), Zn1–O1 212.3(3), Zn1–O2 197.6(3), Zn1–O4 given by the (O1, O4, N5) and (S, O1, O4, N3) which create an angle of
206.8(3), Zn1–N3 209.9(3), Zn2–O1 212.4(3), Zn2–O4 210.5(3), Zn2– about 20ꢀ. Pertinent distances from planes (in pm): (O1, O4, N5) Zn2
N4 209.6(4), Zn2–N5 227.7(3), Zn2–N6 214.0(4), Zn2–N7 210.6(4).
12.8, N4 75.0; (S, O1, O4, N3) Zn2 45.9, N4 22.8.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 75844–75854 | 75851

View Article Online
RSC Advances
Paper
distinctly different binding pockets of the ligand can enforce
specic coordination modes which could be used to deliber-
ately coordinate metal ions with corresponding geometric
preferences for their coordination sphere. A specic potential
can be attributed to complexes of the proligands as it should
also be possible to utilize them for subsequent derivatization
towards the generation of a second binding site with otherwise
not accessible combinations of the underlying amine
components.
Acknowledgements
Fig. 11 Representation of the hydrogen bonding interactions in the
crystal structure of [Zn2(tsc-hydra)(OAc)2]$MeCN$H2O leading to
a chain-like arrangement along the [100] direction. Pertinent distances
(in pm): N1/N2 304.3(5), N2/O1W 295.7(6), O5/O1W 275.0(5),
O1W/N1AN 298.4(9).
This work was in part supported by the Collaborative Research
Centre ChemBioSys (CRC 1127 ChemBioSys) and funded by the
Deutsche Forschungsgemeinscha (DFG). We thank Stefan
Schinkel for assistance in the assignment of the NMR data.
of chain-like aggregation of the complex molecules along the
[100] direction as depicted in Fig. 11. Two such symmetry
related chains buildup the crystal structure with relative
orientations of their planar hydrogen paired ligand back-
References
1 Handbook on Metalloproteins, ed. I. Bertini, A. Sigel and H.
Sigel, Marcel Dekker, New York, 2001.
ꢀ
bones aligned along the crystallographic (011) and (011)
planes. The acetonitrile molecules are located between these
chains such that they have hydrogen bonding contacts with
neighboring chains of the same basic orientation (see
Fig. S27†). The closest contact between chains of different
orientation are p–p interactions of a pyridyl ring (N7) with the
central aromatic ring of an adjacent complex molecule (see
Fig. S28†). Together with additional packing effects due to the
acetonitrile molecule the latter interaction leads to an out-of-
plane distortion of the phenolate oxygen O1 (16 pm) and the
methyl group C9 (18 pm) substituents at the central aromatic
ring (C3 to C8).
2 Handbook of Metalloproteins, ed. A. Messerschmidt, Wiley,
New York, 2001-2011, vol. 1–5.
3 C. Belle, Eur. J. Inorg. Chem., 2003, 4137–4146.
4 J. J. H. Satcher, M. W. Droege, T. J. R. Weakley and
R. T. Taylor, Inorg. Chem., 1995, 34, 3317–3328.
5 S. J. Lippard, Science, 1995, 268, 996–997.
6 B. Zambelli, F. Musiani, S. Benini and S. Ciurli, Acc. Chem.
Res., 2011, 44, 520–530.
7 T. Palzkill, Ann. N. Y. Acad. Sci., 2013, 1277, 91–104.
8 R. E. Stenkamp, Chem. Rev., 1994, 94, 715–726.
´
9 N. Mitic, S. J. Smith, A. Neves, L. Guddat, L. R. Gahan and
G. Schenk, Chem. Rev., 2006, 106, 3338–3363.
10 J. A. Tainer, E. D. Getzoff, J. S. Richardson and
D. C. Richardson, Nature, 1983, 306, 284–287.
Conclusions
A simple and straightforward synthetic approach towards 11 A. Roth and W. Plass, Angew. Chem., Int. Ed., 2008, 47, 7588–
unsymmetric double Schiff-base ligands on the basis of iso- 7591.
lated intermediate mono Schiff-base precursors is presented. 12 M. Carboni and J.-M. Latour, Coord. Chem. Rev., 2011, 255,
The rst step of this synthetic route can generally be handled 186–202.
on a large scale when thiosemicarbazide and semicarbazide 13 S. Matsunaga and M. Shibasaki, Chem. Commun., 2014, 50,
are used as amine components to generate the mono Schiff 1044–1057.
bases. These precursors can be utilized to synthesize a variety 14 I. Bratko and M. Gomez, Dalton Trans., 2013, 42, 10664–
of unsymmetric end-off compartmental double Schiff-base 10681.
ligands with both exible and rigid donor sets. For two exam- 15 D. G. H. Hetterscheid, S. H. Chikkali, B. de Bruin and
ples of the presented ligands their coordination behavior has J. N. H. Reek, ChemCatChem, 2013, 5, 2785–2793.
been studied by the synthesis of appropriate metal complexes. 16 T. Hellmuth, S. Rieckhoff, M. Weiss, K. Dorst, W. Frey and
The mono Schiff-base proligand H2tsc-difo was used to R. Peters, ACS Catal., 2014, 4, 1850–1858.
generate a nickel(II) complex [Ni(tsc-difo)PPh3] with triphenyl- 17 B. Wu, J. C. Gallucci, J. R. Parquette and T. V. RajanBabu,
phosphane as coligand leading to a complex with square- Chem. Sci., 2014, 5, 1102–1117.
planar geometry at the nickel(II) center. As an example from 18 S. W. S. Choy, M. J. Page, M. Bhadbhade and B. A. Messerle,
the series of unsymmetric ditopic ligands we selected H2tsc- Organometallics, 2013, 32, 4726–4729.
hydra due to its combination of a rigid and a exible binding 19 D. C. Powers and T. Ritter, Acc. Chem. Res., 2012, 45, 840–850.
pocket. To explore its coordination behavior the homo- 20 M. Delferro and T. J. Marks, Chem. Rev., 2011, 111, 2450–
dinuclear zinc(II) complex [Zn2(tsc-hydra)(OAc)2] was synthe-
2485.
sized. Interestingly two different coordination geometries were 21 J. P. McInnis, M. Delferro and T. J. Marks, Acc. Chem. Res.,
observed for the two zinc(II) ions indicating that the two
2014, 47, 2545–2557.
75852 | RSC Adv., 2016, 6, 75844–75854
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
22 P. A. Vigato and S. Tamburini, Coord. Chem. Rev., 2004, 248, 49 M. Ciaccia, S. Pilati, R. Cacciapaglia, L. Mandolini and
1717–2128. S. D. Stefano, Org. Biomol. Chem., 2014, 12, 3282–3287.
23 P. A. Vigato, V. Peruzzo and S. Tamburini, Coord. Chem. Rev., 50 T. S. Lobana, R. Sharma, G. Bawa and S. Khanna, Coord.
2012, 256, 953–1114. Chem. Rev., 2009, 253, 977–1055.
24 D. E. Fenton and H. Okawa, Chem. Ber./Recl., 1997, 130, 433– 51 P. J. Jansson, P. C. Sharpe, P. V. Bernhardt and
442. D. R. Richardson, J. Med. Chem., 2010, 53, 5759–5769.
25 A. L. Gavrilova and B. Bosnich, Chem. Rev., 2004, 104, 349– 52 D. R. M. Moreira, A. D. T. de Oliveira, P. A. T. de Moraes
383.
Gomes, C. A. de Simone, F. S. Villela, R. S. Ferreira,
A. C. da Silva, T. A. R. dos Santos, M. C. A. B. de Castro,
V. R. A. Pereira and A. C. L. Leite, Eur. J. Med. Chem., 2014,
75, 467–478.
26 P. J. Steel, Acc. Chem. Res., 2005, 38, 243–250.
27 M. Jarenmark, H. Carlsson and E. Nordlander, C. R. Chim.,
2007, 10, 433–462.
28 P. A. Vigato and S. Tamburini, Coord. Chem. Rev., 2008, 252, 53 L. Blau, R. F. Menegon, G. H. G. Trossini, J. V. D. Molino,
1871–1995.
D. G. Vital, R. M. B. Cicarelli, G. D. Passerini, P. L. Bosquesi
and C. M. Chin, Eur. J. Med. Chem., 2013, 67, 142–151.
54 L. F. Lindoy, G. V. Meehan and N. Svenstrup, Synthesis, 1998,
1029–1032.
55 M. Schatz, M. Leibold, S. P. Foxon, M. Weitzer,
F. W. Heinemann, F. Hampel, O. Walter and S. Schindler,
Dalton Trans., 2003, 8, 1480–1487.
29 K. E. Dalle and F. Meyer, Eur. J. Inorg. Chem., 2015, 3391–
3405.
30 G. Belle, G. Gellon, C. Scheer and J.-L. Pierre, Tetrahedron
Lett., 1994, 35, 7019–7022.
31 M. Suzuki, S. Fujinami, T. Hibino, H. Hori, Y. Maeda,
A. Uehara and M. Suzuki, Inorg. Chim. Acta, 1998, 283,
124–135.
56 R. W. W. Hoo, COLLECT, Data Collection Soware, Nonius
BV, Del, Netherlands, 1998.
32 T. Koga, H. Furutachi, T. Nakamura, N. Fukita, M. Ohba,
¯
K. Takahashi and H. Okawa, Inorg. Chem., 1998, 37, 989–996. 57 Z. Otwinowski and W. Minor, in Methods in Enzymology,
33 D. E. Fenton, Chem. Soc. Rev., 1999, 28, 159–168.
34 R. Than, A. A. Feldmann and B. Krebs, Coord. Chem. Rev.,
1999, 182, 211–241.
Macromolecular Crystallography, Part A, ed. C. W. Carter
and R. M. Sweet, Academic Press, New York, 1997, vol. 276,
pp. 307–326.
35 H. Adams, L. R. Cummings, D. E. Fenton and P. E. McHugh, 58 SADABS 2.10, Bruker-AXS Inc., Madison, Wisconsin, USA,
Inorg. Chem. Commun., 2003, 6, 19–22. 2002.
36 Y. Tachi, K. Aita, S. Teramae, F. Tani, Y. Naruta, S. Fukuzumi 59 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.,
and S. Itoh, Inorg. Chem., 2004, 43, 4558–4560. 2008, 64, 112–122.
37 R. A. Peralta, A. Neves, A. J. Bortoluzzi, A. Casellato, A. dos 60 L. Sobczyk, S. J. Grabowski and T. M. Krygowski, Chem. Rev.,
Anjos, A. Greatti, F. R. Xavier and B. Szpoganicz, Inorg.
Chem., 2005, 44, 7690–7692.
2005, 105, 3513–3560.
61 P. Gilli, V. Bertolasi, V. Ferretti and G. Gilli, J. Am. Chem. Soc.,
2000, 122, 10405–10417.
¨
38 M. F. Anderlund, J. Hogblom, W. Shi, P. Huang, L. Eriksson,
˚
´
H. Weihe, S. Styring, B. Akermark, R. Lomoth and 62 J. S. Casas, M. S. Garcıa-Tasende and J. Sordo, Coord. Chem.
A. Magnuson, Eur. J. Inorg. Chem., 2006, 5033–5047.
39 Y.-W. Ren, J.-X. Lu, B.-W. Cai, D.-B. Shi, H.-F. Jiang, J. Chen, 63 T. S. Lobana, R. Sharma, G. Bawa and S. Khanna, Coord.
D. Zheng and B. Liu, Dalton Trans., 2011, 40, 1372–1381. Chem. Rev., 2009, 253, 977–1055.
40 M. Jarenmark, M. Haukka, S. Demeshko, F. Tuczek, 64 R. Alonso, E. Bermejo, A. Custineiras, T. Perez and
Rev., 2000, 209, 197–261.
˜
´
L. Zuppiroli, F. Meyer and E. Nordlander, Inorg. Chem.,
2011, 50, 3866–3887.
R. Carballo, Z. Anorg. Allg. Chem., 1997, 623, 818–824.
¨
65 H. Gunther, NMR Spectroscopy, Wiley-VCH, Weinheim, 3rd
41 G. N. Ledesma and S. R. Signorella, Tetrahedron Lett., 2012,
53, 5699–5702.
edn, 2013.
ˇ
66 K. G. Orrell, A. G. Osborne, J. O. Prince, V. Sik and
42 L. J. Daumann, L. Marty, G. Schenk and L. R. Gahan, Dalton
Trans., 2013, 42, 9574–9584.
43 D. Wang, S. V. Lindeman and A. T. Fiedler, Inorg. Chim. Acta,
2014, 421, 559–567.
D. K. Vellianitis, Eur. J. Inorg. Chem., 2000, 2000, 383–391.
67 A. B. P. Lever, Inorganic Electronic Spectrocopy, Elsevier,
Amsterdam, 2nd edn, 1984.
68 V. Philip, V. Suni, M. R. P. Kurup and M. Nethaji, Polyhedron,
2004, 23, 1225–1233.
44 B. Das, H. Daver, M. Pyrkosz-Bulska, E. Persch, S. K. Barman,
R. Mukherjee, E. Gumienna-Kontecka, M. Jarenmark, 69 N. T. Akinchan, R. Akinchan, U. J. Ibok, L. P. Battaglia,
F. Himo and E. Nordlander, J. Inorg. Biochem., 2014, 132, 6–17.
45 K. C. Gupta and A. K. Sutar, Coord. Chem. Rev., 2008, 252,
1420–1450.
A. Bonamartini Corradi and P. Drozdzewski, J. Crystallogr.
Spectrosc. Res., 1992, 22, 741–753.
70 T. S. Lobana, P. Kumari, G. Hundal and R. J. Butcher,
Polyhedron, 2010, 29, 1130–1136.
46 A. W. Kleij, Eur. J. Inorg. Chem., 2009, 193–205.
47 A. Roth, E. T. Spielberg and W. Plass, Inorg. Chem., 2007, 46, 71 R. Prabhakaran, P. Kalaivani, P. Poornima, F. Dallemer,
4362–4364.
G. Paramaguru, V. V. Padma, R. Renganathan, R. Huang
¨
48 A. Roth, A. Buchholz, M. Rudolph, E. Schutze, E. Kothe and
and K. Natarajan, Dalton Trans., 2012, 41, 9323–9336.
W. Plass, Chem.–Eur. J., 2008, 14, 1571–1583.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 75844–75854 | 75853

View Article Online
RSC Advances
Paper
¨
72 O. Kuhl, in The Range of Chemical Shis, Coupling Constants, 75 O. Takahashi, Y. Kohno and M. Nishio, Chem. Rev., 2010,
¨
and What Inuences Each, ed. O. Kuhl, Springer-Verlag,
110, 6049–6076.
Berlin Heidelberg, 2008, ch. 2, pp. 7–23.
73 L. Pazderski, Annu. Rep. NMR Spectrosc., 2013, 80, 33–179.
76 W. Plass, Z. Anorg. Allg. Chem., 1997, 623, 461–477.
77 W. Plass, Z. Anorg. Allg. Chem., 1994, 620, 1635–1644.
74 T. Steiner and G. Koellner, J. Mol. Biol., 2001, 305, 535–557. 78 J. B. Mandel, C. Maricondi and B. E. Douglas, Inorg. Chem.,
1988, 27, 2990–2996.
75854 | RSC Adv., 2016, 6, 75844–75854
This journal is © The Royal Society of Chemistry 2016