DSpace at VNU: (ReO)-O-V and (ReNPh)-N-V complexes with pentadentate benzamidines - Synthesis, structural characterization and DFT evaluation of isomeric complexes

Accepted Manuscript
ReVO and ReVNPh Complexes with Pentadentate Benzamidines – Synthesis,
Structural Characterization and DFT Evaluation of Isomeric Complexes
Hung Huy Nguyen, Pham Chien Thang, Ulrich Abram
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DOI:
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S0277-5387(15)00434-9
/>POLY 11465

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Polyhedron

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Accepted Date:

28 June 2015
31 July 2015

Please cite this article as: H. Huy Nguyen, P. Chien Thang, U. Abram, ReVO and ReVNPh Complexes with
Pentadentate Benzamidines – Synthesis, Structural Characterization and DFT Evaluation of Isomeric Complexes,
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ReVO and ReVNPh Complexes with Pentadentate Benzamidines – Synthesis,

Structural Characterization and DFT Evaluation of Isomeric Complexes

Hung Huy Nguyen,a)* Pham Chien Thang,b) Ulrich Abramb)*
a)

Department of Chemistry, Hanoi University of Science, 19 Le Thanh Tong, Hanoi,

Vietnam.
b)

Freie Universität Berlin, Institute of Chemistry and Biochemistry, Fabeckstr. 34-36, D-

14195 Berlin, Germany

Abstract. Novel, potentially pentadentate ligands (H3L) for an optimal coordination of
{MVO}3+ and {MV(NPh)}3+ cores (M = Re, Tc) have been tailored by a computer-aided
procedure. They can be prepared by reactions of 2-aminobenzyliminodiacetic acid
diethylester with N,N-[(dialkylamino)(thiocarbonyl)]benzimidoyl chlorides and subsequent
hydrolysis. The ligands react with [ReOCl3(PPh3 )2] or [Re(NPh)Cl3(PPh3)2] under triple
deprotonation and form compounds of the general compositions [ReO(L)] and
[Re(NPh)(L)], respectively. The organic ligands occupy the remaining five coordination
positions of the {ReO}3+ and {Re(NPh)}3+ cores in all compounds studied. The
phenylimido complexes hydrolyze in basic media under formation of their oxidorhenium(V)
analogs.

Keywords: Rhenium, Pentadentate ligands, Oxido complexes, Imido complexes, X-ray
structure, DFT

Corresponding Autors:

(Hung Huy Nguyen)
(Ulrich Abram)

1


1. Introduction
Beside several other applications, rhenium compounds currently attract interest because
of potential applications of complexes of the isotopes 186Re and

188

Re in radiotherapy [1-6].

Additionally, coordination compounds of rhenium are frequently used as non-radioactive
models for development of technetium radiopharmaceuticals [7]. In this context, there is a
permanent need for efficient chelating systems, which form stable and/or kinetically inert
complexes with rhenium or technetium [8]. Such a robust coordination sphere is a
‘chemical pre-requisite’ for resisting the competition of other potential ligand systems,
which are present in all biological fluids in a huge amount and will meet them on their way
to the target organ. Pentadentate ligands should be ideal chelators for the stabilization of the
frequently formed {ReO}

3+

3+

core and its analogous phenylimido {ReNPh}

core.

Nevertheless, hitherto there is only a limited number of structurally well-characterized
rhenium or technetium complexes with pentadentate ligands reported and particularly such
compounds were not in the focus of related nuclearmedical research [9-13]. This may
possibly be understood by the fact that the syntheses of pentadentate ligands are frequently
related to multi-step procedures, which are too time-consuming for the preparation of only
one single molecule with uncertain biodistribution features. In the light of another strategy,
which focuses on the synthesis of a ‘bioconjugation kit’ [14], however, any effort in the
synthesis of a robust ‘multi-use ligand’ seems to be justified. Following this approach, first
99m

Tc or 186,188Re complexes with a strong chelator (having an anchor group in its periphery)

are produced. This pre-formed radioactive label can then be coupled in a second step with
arbitrary peptide-based biomolecules.
Recently, we reported about such a pentadentate ligand system based on
thiocarbamoylbenzamidines, which provides an anchor for the coupling of peptides, and its

2


rhenium and technetium complexes (H3L* and [M(L*)] in Scheme 1) [14]. Such
multidentate ligands can be prepared from benzimidoyl chlorides and functionalized
primary amines [14-17].

Scheme 1. Pentadentate benzamidines and their ReO complexes.
In the present work, we report about the syntheses of similar pentadentate
dialkylamino(thiocarbonyl)benzamidines (H3L
3+

Morph

Et

, and H3L ), which are expected to form
3+

more stable complexes with {ReO} and {ReNPh} cores.

2. Results and Discussion
2.1. Computational Studies
In order to optimize the coordination abilities of the pentadentate benzamidines by a
further increase of the stability of the formed chelates, we searched for alternative ligands.
With regard to the time-consuming syntheses, we decided to estimate the potential of
another promising candidate of a pentadentate ligand (H3L) first by DFT calculations [18].
H3L* and H3L are related ligand systems. They provide the same donor atom constellations,
but with a replaced CH2 spacer in their backbone (Scheme 1). Thus, we calculated the over-


all energies for optimized geometries of the diethyl derivatives [ReO(L*Et)] and [ReO(LEt)].
The results of the geometrical optimization obtained for [ReO(L*Et)] can directly be
compared with the X-ray data of the compound, which are contained contained in ref. 14.
The optimized parameters are in good agreement with the experimental ones. The bond
lengths differ by less than 0.04 Å, whereas the angles by 4 o or less. A Table with details of
the experimental and calculated structural data is contained in the Supplementary Material.
On the basis of the good agreement between the experimental and calculated data for
[ReO(L*Et)], we extended the calculations to the complex [ReO(LEt)] in order to estimate
stabilizing or destabilizing effects due to the modifications in the coordination sphere of the
metal. A comparison of the energies of optimized structures of the two structural isomers
[ReO(L*Et)] and [ReO(LEt)] strongly suggests that the latter compound is more stable by a

Table 1. Energies of optimized geometries of [ReO(LEt)] and [ReO(L*Et)] at different
levels of DFT.
Basis sets

DFT

E (Hartree)

∆E[a]

method

[ReO(LEt)]

[ReO(L* Et)]

kJ/mol

LANL2DZ 6-31G*

PBE0
B3LYP

-1961.73297
-1963.57025

-1961.72425
-1963.56175

-22.89
-22.31

LANL2DZ 6-31G**

PBE0
B3LYP

-1961.76982
-1963.60699

-1961.76122
-1963.59860

-22.57
-22.04

LANL2TZ

PBE0
B3LYP

-1961.79351
-1963.63174

-1961.78475
-1963.62318

-22.99
-22.46

Re

C,H,N,O,S

6-31G**

[a] ∆E = E[ReO(L)] – E[ReO(L*)]
value of about 22 – 23 kJ/mol. This energetic difference is nearly independent of the
employed DFT methods as well as of the basis set combinations (Table 1). These facts
together with the slight discrepancy between the experimental and optimized bonding
parameters in [ReO(L*Et) underlines the reliability of performed DFT calculations and

4


encouraged us to undertake the syntheses of ligands of the type H3 L and their rhenium
complexes.
2.2. Ligand Synthesis
Ligands of the type H3L have been obtained in multistep syntheses from 2-nitrobenzylamine as is shown in Scheme 2. In the first step, 2-nitrobenzylamine reacts with an
excess of bromoacetic acid ethylester in dry MeCN under reflux and in the presence of a
base like K2CO3. The reaction is catalyzed by solid KI, which activates the bromoacetic
acid ethylester. This iodide-catalyzed coupling proceeds sufficiently fast for the synthesis
of 1. The disubstituted product is formed almost quantitatively within 10 h when an excess
of 25% bromoacetic acid ethylester is used. It should be mentioned that a similar procedure
with aromatic amines requires more drastic conditions [14].

Scheme 2. The synthesis of the pentadentate ligand H3L.

The reduction of the nitro group of 1 can be performed either by H2 gas with a Pd/C

catalyst or with Raney nickel in an ethylacetate/methanol mixture. The first reaction must
be quenched after 5 h in order to minimize the formation of side-products due to the
cleavage of the N-benzyl bond and gives an overall yield of 55% after purification by
column chromatography (silica gel) with ethyl acetate/n-hexane (1:1). More effective is the


use of the Raney nickel. The reduction proceeds slowly but is much cleaner under the same
conditions. After 24 h, the reaction is complete and no side-products can be detected by
NMR spectroscopy. The final ligands H3L are best prepared by reactions of 2 with the
corresponding benzimidoyl chlorides to form 3 and subsequent hydrolysis of these
compounds with NaOH in methanol. Neutralization of the products of such reactions with
citric acid gives the pentadendate ligands H3L in high yields. An alternative route, which
contains the hydrolysis of the ester in the first step produces a number side products due to
the low solubility of the dicarboxylic acid in non-alcoholic solvents such as THF or acetone,
which are normally used for preparation of benzamidine ligands [14,19,20].
The IR spectra of H3L show strong, broad bands for the νOH stretches in the region between
3500 cm-1 and 2500 cm-1. Very strong absorptions around 1720 cm-1 are assigned to νC=O
vibrations, which are well separated from the strong absorptions of the ν C=N stretches in the
1616 cm-1 region [21-24]. The 1H NMR spectra of H3L are characterized by two singlets
around 3.45 ppm and 4.00 ppm, which are assigned to the methylene protons of NCH2CO
and PhCH2N, respectively. Broad singlets at 9.40 ppm and 11.50 ppm belong to NH and
COOH resonances. The hindered rotation around the CS-NR1R2 bonds, which is found for
many thiocarbamoylbenzamidines, is also observed for H3L. This results in magnetic
inequality of the two residues R, and consequently the 1H NMR spectrum of H3LMorph
shows two overlapping signals with complex coupling patterns of two NCH2 groups and
two OCH2 groups of the morpholine residue. In the case of H3LEt, two set of well resolved
signals corresponding two ethyl groups of -NEt2 residue are observed. The +ESI mass
spectra of the ligands show clear patterns with expected molecular ion [M+H]+ peaks and
confirm their composition unambiguously.

2.3. Oxidorhenium(V) complexes

6


Representatives of the novel ligand system H3L react with the sparingly soluble starting
material [ReOCl3(PPh3)2] in MeOH/CH2Cl2 under formation of red crystalline solids of the
composition [ReO(L)] (4) in high yields (Scheme 3). The reactions are slow at ambient
temperature, but can be accelerated by the addition of a supporting base such as Et3N and

Scheme 3. Reaction of H3L with [ReOCl3(PPh3)2].
heating. The products are readily soluble in DMSO or DMF, less soluble in CH2 Cl2 or
CHCl3 and almost insoluble in alcohols.
The IR spectra of 4 show no bands of OH or NH stretches, which reflects the presence of
the triply deprotonated forms of the ligands. Additionally, the shift of the νC=N band from
about 1615 cm-1 in the spectra of the uncoordinated compounds to the region around
1535 cm-1 indicates the formation of a benzamidinate chelate ring. Two different
absorptions of ν C=O stretches are observed around 1713 cm-1 and 1696 cm-1 and can be
assigned to the two nonequivalent carboxylate groups in the molecules. The presence of
Re=O bonds is confirmed by strong absorptions at 964 cm-1 for 4Morph and at 962 cm-1 for
4Et. They appear in the expected range for octahedral ReVO complexes with trans O=Re-O
arrangement [7,25,26].
The 1H NMR spectra of 4 in DMSO-d 6 are characterized by three pairs of doublets with
typical geminal coupling constants corresponding to the protons of three methylene groups
in the chelate rings. While the two PhCH2N protons resonate at 3.65 and 3.71 ppm, the


resonances of the four COCH2N protons appear in the range between 4.6 ppm to 5.6 ppm.
The rigid structure of NR1R2 residues in corresponding thiocarbamoylbenzamidine
complexes has previously been reported and is also observed in 4 [14,25]. In the 1H NMR

spectrum of 4Morph, four signals, two broadened doublets at 3.89 ppm and 3.97 ppm and
another two overlapped in a multiplet at 3.84 ppm, corresponding to

the four NCH2

protons are observed. Those of the four OCH2 protons give two broadened doublets at 4.30
and 4.51 ppm and a multiplet at 4.58 ppm. Similarly, the rigid structure of NEt2 results in
four magnetically unequalent CH2 protons, which correspond to four well-resolved double
quartets with a geminal coupling constant of J1 = 14 Hz and a vicinal coupling constant of
J2 = 7.0 Hz. The 1H NMR spectra of 4 recorded in DMSO-d 6 are quite different from those
recorded in CDCl3 with respect to the chemical shift of the NR1R2 residues and the CH2
protons in the chelate rings. In the case of complex 4Morph, the spectrum in CDCl3 shows an
overlapped multiplet at 3.92 ppm, which is assigned to four NCH2 protons, and two well
separated multiplets at 4.22 ppm, 4.36 ppm and one overlapping multiplet at 4.51 ppm,
which are assigned to the four OCH2 protons in the morpholinyl residue.
Figure 1 depicts the molecular structure of 4Morph. Some important bond lengths and angles
are summarized in Table 2. The rhenium atom has adopted a distorted octahedral

Figure 1. Molecular structure of [ReO(LMorph)] (4Morph) [32]. Hydrogen atoms are omitted
for clarity.


coordination environment, in which five positions of the coordination sphere are occupied
by the donor atoms of the ligand {LMorph}3- and the remaining position is occupied by a
terminal oxido ligand. The molecular structure of 4Morph confirms the presence of the triply
deprotonated form of the organic ligand. One of the carboxylic groups (O68) is in trans
position to the oxido ligand, while O64 occupies a cis position. This is consistent with the
two C=O bands observed in the IR spectrum of 4Morph. The Re-O68 bond length is slightly
shorter than the Re-O64 distance, reflecting some transfer of electron density from the
rhenium oxygen double bond to this bond [26,27]. The partial double bond character of the

C4–N5 bond may make the six-membered chelate ring containing the aminobenzylamine
Table 2. Selected experimental bond lengths (Å) and angles (deg) in [ReO(LMorph)] (4Morph)
Re–O10

1.672(7)

Re–O64

2.055(7)

C62–O63

1.20(1)

Re–S1

2.309(2)

Re–O68

2.040(7)

C62–O64

1.32(1)

Re–N5

2.037(8)

S1–C2

1.76(1)

C66–O67

1.22(1)

Re–N8

2.207(7)

C4–N5

1.35(1)

C66–O68

1.29(1)

O10–Re– S1

103.4(2)

O10–Re–O64

94.8(3)

N5–Re–O64

166.2(3)

O10–Re–N5

95.8(3)

O10–Re–O68

164.4(3)

S1–Re–N5

94.6(2)

O10–Re–N8

88.2(3)

S1–Re–N8

165.4(2)

N8–Re–N5

93.0(3)

unit rigid and, thus, it is prevented from switching between boat and chair conformation as
is suggested by the splitting of PhCH2N signals of the ring in the 1H-NMR spectrum of the
compound.

2.3. Phenylimidorhenium(V) complexes with H3L
The rhenium(V) phenylimido core, which is isoelectronic with the rhenium(V) oxido core,
is expectedly also stabilized by the H3L chelator system. However, reactions of H3L with

9


[Re(NPh)Cl3(PPh3)2] in CH2Cl2 in the presence of a supporting base at room temperature
result in side-products.

Scheme 4. Reaction of H3L with [Re(NPh)Cl3(PPh3)2].
Typically, beside the phenylimido complex [Re(NPh)(L)] (5) (Scheme 4), the reaction
mixtures contain the oxo complexes 4 and other (phosphine containing) side products.
Heating of the reaction mixture for a prolonged reaction time results in a complete
hydrolysis of 5 and the formation of 4 as the sole product. Despite the fact that the addition
of a base like Et3N accelerates the hydrolysis of 5, its addition was required for the
deprotonation of H3L in a reasonable time. While compound 5 Et seems to hydrolyze very
quickly and could only be detected in the reaction mixture by MS spectroscopy, the
hydrolysis of 5Morph was slow. The pure complex 5 Morph can be obtained by a
chromatographic purification (silica gel, CHCl3/hexane) of the product mixture obtained at
ambient temperatures. A similar hydrolysis has been observed before for reactions of
[Re(NPh)Cl3(PPh3)2] with ligands of the type H3L* (Scheme 1). In this case, any attempts
to isolate the phenylimido species failed, and only the oxido complexes were obtained in
good yields [14]. It is worth to notice that without a base, no hydrolysis of the complex
5Morph could be detected in the solution.
The IR spectrum of 5Morph is characterized by very strong, broad absorptions at 1700 cm-1,
which are typical for coordinated carboxylate groups. A strong bathochromic shift of the
νC=N band is also observed. The 1H NMR spectrum of 5Morph has principally the same

pattern as that of 4Morph except the additional aromatic signals, which belong to the
phenylimido ligand.

Figure 2. Molecular structure of [Re(NPh)(LMorph)] (5Morph) [32]. Hydrogen atoms are
omitted for clarity.

Table 3. Selected experimental bond lengths (Å) and angles (deg) in [Re(NPh)(LMorph)]
(5Morph)
Re–N10

1.69(1)

Re–O64

2.090(7)

C62–O63

1.22(1)

Re–S1

2.339(3)

Re–O68

2.03(1)

C62–O64

1.29(1)

Re–N5

2.05(1)

S1–C2

1.73(1)

C66–O67

1.22(1)

Re–N8

2.16(1)

C4–N5

1.34(1)

C66–O68

1.27(1)

N10–Re– S1

97.8(4)

N10–Re–O64

88.9(4)

N5–Re–O64

166.2(4)

N10–Re–N5

101.3(4)

N10–Re–O68

168.6(4)

S1–Re–N5

93.6(3)

N10–Re–N8

94.4(4)

S1–Re–N8

165.1(3)

N8–Re–N5

92.4(4)

Single crystals of 5Morph suitable for an X-ray study were obtained by slow evaporation
of CH2Cl2/n-hexane mixtures. Figure 2 illustrates the molecular structure of this
compound. Selected bond lengths and angles are given in Table 3. The structure reveals a
distorted octahedral environment around the rhenium atom containing the coordinated


{LMorph}3- as triply deprotonated, pentadentate ligand as discussed for the corresponding
oxido complex 4Morph. The remaining position in the octahedral sphere is occupied by a
phenylimido ligand, which is coordinated in trans position to one of the carboxylate groups.
The Re–N–C bond of the phenylimido ligand is almost linear with a value of 167.3(9)o. The
Re-N10 bond length of 1.69(1) Å in 5Morph is in the expected range of rhenium-nitrogen
double bonds [7]. The bonding situation inside the ligand {L}3- of the complexes 5Morph is
generally similar to that of the oxido compound.

3. Conclusions
The pentadentate ligand H3L, which has been developed by a computer-aided procedure
is well suitable for the formation of stable complexes with the {ReO}3+ core. It could be
demonstrated that minor modifications in the skeleton of such pentadentate ligands may
have marked influence on the stability of the formed complexes.

Scheme 5. Derivative of H3L with an anchor group for bioconjugation.
The optimized ligands are good candidates as chelating units for ‘bioconjucation kits’ on
3+

3+

the basis of {ReO} or {TcO} complexes. A possible position for the bioconjugation is
shown in Scheme 5. Corresponding studies for the synthesis of such ligands, which possess

a suitable anchor group for the coupling of a peptide-based biomolecule, and their rhenium
and technetium complexes are planed for the future in our laboratories.


4. Experimental
4.1. Materials
All chemicals used in this study were reagent grade and used without further purification.
Solvents were dried and used freshly distilled unless otherwise stated. [ReOCl3(PPh3)2] and
[Re(NPh)Cl3(PPh 3)2] were prepared by standard procedures [28,29]. The syntheses of the
N,N-[(diethylamino)(thiocarbonyl)]benzimidoyl chloride and [(morpholinyl)(thiocarbonyl)]benzimidoyl chloride were performed by the procedure of Beyer et al. [30].

4.2. Physical Measurements
Infrared spectra were measured as KBr pellets on a Shimadzu FTIR-spectrometer between
-1

400 and 4000 cm . NMR spectra were taken with JEOL 400 MHz and Bruker 500 MHz
multinuclear spectrometers. Positive ESI mass spectra were measured with an Agilent 6210
ESI-TOF (Agilent Technology) mass spectrometer. All MS results are given in the form:
m/z, assignment. Elemental analysis of carbon, hydrogen, nitrogen and sulfur were
determined using a Heraeus vario EL elemental analyzer.

4.3. Syntheses of the ligands
4.3.1. 2-Nitrobenzyliminodiacetic acid diethylester (1)
2-Nitrobenzylamine (6.086 g, 40 mmol), ethyl bromoacetate (11.0 mL, 99 mmol), a
mixture of finely powdered K2CO3 (16.8 g, 122 mmol), KI (1.0 g) and 100 mL of dry
MeCN were heated under reflux for 10 h. After being cooled to room temperature, the
mixture was filtered and the solvent was removed under reduced pressure. The excess of
ethyl bromoacetate was removed by heating the mixture to 80oC under a pressure of about
20 mmHg. The product was obtained as a slightly yellow oil. Yield 96 % (12.45 g).
Elemental analysis: Calcd. for C15H20N2O6: C, 55.55; H, 6.22; N, 8.64%. Found: C, 55.36;

H, 6.31; N, 8.51%. 1H NMR (400 MHz, CDCl3, ppm): 1.25 (t, J = 7.1 Hz, 6H, CH2CH3),

13


3.55 (s, 4H, NCH2CO), 4.17 (q, 7.1 Hz, 4H, CH2CH3), 4.26 (s, 2H, PhCH2N), 7.41-7.87 (m,
4H, aromat. H).

4.3.2. 2-Aminobenzyliminodiacetic acid diethylester (2)
A mixture of compound 1 (4.865 g, 15 mmol), Raney nickel (® 3202 Sigma Aldrich, about
5 g), MeOH (30 mL) and ethyl acetate (5 mL) was stirred under an atmosphere of hydrogen
at room temperature for 24 h. The reaction mixture was filtered and the organic solvents
were completely removed under vacuum to give the product in almost quantitative yields as
a yellow oil. Elemental analysis: Calcd. for C15H22N2O4: C, 61.21; H, 7.53; N, 9.52%.
1

Found: C, 61.01; H, 7.46; N, 9.49%. H NMR (400 MHz, CDCl3, ppm): 1.27 (t, J = 7.1 Hz,
6H, OCH2CH3), 3.47 (s, 4H, CH2CO), 3.85 (s, 2H, PhCH2N), 4.16 (q, 7.1 Hz, 4H,
OCH2CH3), 6.62- 7.09 (m, 4H, aromat. H).

4.3.3.

N,N-Dialkylaminothiocarbonyl-N’-{phenylene-(2-methyliminodiacetic

acid

diethylester)} benzamidines (3)
Solid benzimidoyl chloride (5.0 mmol) was added to a mixture of 2 (1.47 g, 5.0 mmol) and
triethylamine (1,51 g, 15 mmol) in 20 mL of dry THF. The mixture was stirred for 4 h at
room temperature. The formed precipitate of NEt3 · HCl was filtered off and the filtrate was

evaporated under reduced pressure to dryness. The residue was washed with diethyl ether
(20 mL) and dried in vacuum to give 3 as yellow solids.
3Morph: Yield 90% (2.304 g). Elemental analysis: Calcd. for C27H34N4O5S: C, 61.5; H, 6.5;
N, 10.6; S, 6.1%. Found: C, 61.0; H, 6.3; N, 10.4; S, 6.2%. IR (KBr, cm-1): 3248 (br, s),
2949 (w), 2875 (w), 1756 (s), 1724 (s), 1629 (s), 1539 (s), 1481 (m), 1450(m), 1183 (m),
1

1091 (m), 1024 (m), 756 (s). H NMR (500 MHz, CDCl3, ppm): 1.25 (t, J = 7.0 Hz, 6H,

14


OCH2CH3), 3.50 (s, 4H, NCH2CO), 3.72 (m, 4H, NCH2), 3.98 (q, J = 7.0 Hz, 4H,
OCH2CH3), 4.05 (s, br, 2H, PhCH2N), 4.11 (m, 4H, OCH2), 6.95-7.77 (m, 9H, aromat. H),
+

10.23 (s, 1H, NH). +ESI MS (CH2Cl2): 527.2 (100% base peak, [M+H] ); 559.2 (20% base
peak, [M+Na]+).
3Et: Yield 90% (2.304 g). Elemental analysis: Calcd. for C27H36N4O4S: C, 63.2; H, 7.1; N,
-1

10.9; S, 6.3%. Found: C, 63.0; H, 7.2; N, 10.7; S, 6.4%. IR (KBr, cm ): 3267 (br, s), 2978
(w), 2935 (w), 1751 (s), 1726 (s), 1630 (s), 1537 (s), 1489 (m), 1452(m), 1193 (m), 1080
(m), 1024 (m), 754 (s). 1H NMR (500 MHz, CDCl3, ppm): 1.18 (t, br, 6H, NCH2CH3), 1.24
(t, J = 7.0 Hz, 6H, OCH2CH3), 3.50 (s, 4H, NCH2CO), 3.69 (t, J = 7.0 Hz, 2H, NCH2CH3),
3.95 (t, J = 7.0 Hz, 2H, NCH2CH3), 4.00 (q, J = 7.0 Hz, 4H, OCH2CH3), 4.03 (s, br, 2H,
PhCH2N), 6.98-7.79 (m, 9H, aromat. H), 10.15 (s, 1H, NH). +ESI MS (CH2Cl2): 513.2
(100% base peak, [M+H]+); 535.2 (30% base peak, [M+Na]+); 551.2 (5% base peak,
[M+K]+).

4.3.4.

N,N-Dialkylaminothiocarbonyl-N’-{phenylene-(2-methyliminodiacetic

acid)}

benzamidines (H3 L)
NaOH (50 mmol) was added to a solution of compound 3 (4.0 mmol) in MeOH (20 mL)
and the reaction mixture was stirred overnight. After reducing the volume to about 5 mL,
20 mL of brine and citric acid monohydrate (1.05 g, 50 mmol) were added. The resulting
suspension was extracted twice with portions of 20 mL THF. The organic phases were
combined and evaporated to dryness. The raw products were dissolved in CH2Cl2/MeOH
(1/1, v/v) and recrystallized by slow evaporation of such solutions.
H3LMorph: Yield 84% (1.574 g). Elemental analysis: Calcd. for C23H26N4O5S: C, 58.7; H, 5.6;
-

N, 11.9; S, 6.8%. Found: C, 58.4; H, 5.6; N, 12.3; S, 6.7%. IR (KBr, cm 1): 3201 (br, s), 1720
(br, s), 1616 (s), 1527 (s), 1450 (m), 1427 (s), 1277 (s), 1227 (s), 1110 (s), 1026 (m), 764 (m), 698
(m). 1H NMR (400 MHz, CDCl3, ppm): 3.44 (s, 4H, NCH2CO), 3.66 (m, 4H, NCH2), 3.86

15


(m, 4H, OCH2), 4.02 (s, 2H, PhCH2N), 6.93- 7.48 (m, 9H, aromat. H), 9.38 (s, 1H, NH),
+

11.45 (s, br, 2H, COOH). +ESI MS (CH2Cl2): 471.2 (100% base peak, [M+H] ); 493.1
(65% base peak, [M+Na] +).
H3LEt: Yield 81% (1.482 g). Elemental analysis: Calcd. for C23H28N4O4S: C, 60.5; H, 6.2; N,
12.3; S, 7.0%. Found: C, 60.1; H, 6.2; N, 12.5; S, 6.9%. IR (KBr, cm-1): 3214 (br, s), 1718

(br, s), 1615 (s), 1530 (s), 1457 (m), 1450(s), 1272 (s), 1122 (s), 1095 (s), 1026 (m), 770
1

(m), 697 (m). H NMR (400 MHz, CDCl3, ppm): 1.09 (t, J = 7.0 Hz, 3H, NCH2CH3), 1.13
(t, J = 7.0 Hz, 3H, NCH2CH3), 3.45 (s, 4H, NCH2CO), 3.60 (t, J = 7.0 Hz, 2H, NCH2CH3),
3.71 (t, J = 7.0 Hz, 2H, NCH2CH3), 4.04 (s, br, 2H, PhCH2N), 6.90-7.6 (m, 9H, aromat. H),
9.36 (s, 1H, NH), 11.51 (s, br, 2H, COOH). +ESI MS (CH2Cl2): 457.1 (35% base peak,
+

+

[M+H] ); 479.2 (100% base peak, [M+Na] ).

4.3.5. [ReO(L)] (4)
H3L (0.1 mmol) in 3 mL of MeOH and 3 drops of Et3N were added to a stirred solution of
[ReOCl3(PPh 3)2] (83.2 mg, 0.1 mmol) in 5 mL CH2Cl2. The reaction mixture was heated
under reflux for 30 min. After being cooled to room temperature, the reaction mixture was
slowly evaporated, which resulted in the precipitation of the red crystalline complexes 4.
The products were filtered off and recrystallized from CH2Cl2/MeOH. Reactions of
equimolar amounts of H3L and (NBu4)[ReOCl4] in MeOH result in the same products, but
with slightly lower yields.
[ReO(LMorph)] (4Morph).

Yield 70% (46.9 mg). Elemental analysis: Calcd.

for

C23H23N4O6SRe: C, 41.2; H, 3.5; N, 8.4; S, 4.8%. Found: C, 41.2; H, 3.3; N, 8.3; S, 4.8%. IR
-

(KBr, cm 1): 3050 (w), 2962 (w), 2934 (w), 1713 (vs), 1696 (vs), 1535 (s), 1481 (m), 1434
(m), 1296 (m), 1226 (w), 1119 (m) 964 (m), 933 (m), 910 (m), 771 (m), 717 (w). 1H NMR
(500 MHz, DMSO-d6, ppm): 3.65 (d, J = 18.5 Hz, 1H, PhCH2N), 3.72 (d, J = 18.5 Hz, 1H,
PhCH2N), 3.84 (m, br 2H, NCH2), 3.89 (d, br 1H, NCH2), 3.97 (d, br, 1H, NCH2), 4.30(d,

16


br, 1H, OCH2), 4.51 (d, br, 1H, OCH2), 4.58 (m, br, 2H, OCH2), 4.63 (d, J = 15.0 Hz, 1H,
NCH2CO), 4.97 (d, J = 15.0 Hz, 1H, CH2CO), 5.47 (d, J = 12.5 Hz, 1H, NCH2CO), 5.58 (d, J
13

= 12.5 Hz, 1H, NCH2CO), 6.84-7.59 (m, 9H, aromat. H). C NMR (DMSO-d6, ppm): 50.86,
50.93 (NCH2), 61.64 (PhCH2N), 66.68, 66.72 (OCH2), 68.06, 68.78 (NCH2CO), 125.58,
126.65, 128.11, 128.87, 130.71, 131.64, 132.20, 133.98, 135.97(Caromat.), 152.73 (Caromat.-N),
168.50 (C=N), 173.68, (C=O), 175.17 (C=O), 182.32 (C=S). +ESI MS (CH2Cl2): 671.2
+

(100% base peak, [M+H] ).
[ReO(LEt)] (4Et): Yield 74% (48.0 mg). Elemental analysis: Calcd. for C23H25N4O5SRe: C,
42.1; H, 3.8; N, 8.5; S, 4.9%. Found: C, 42.3; H, 3.6; N, 8.3; S, 4.7%. IR (KBr, cm-1): 3055
(w), 2938 (w), 1712 ( vs), 1695 (vs), 1533 (s), 1475 (m), 1297 (m), 1121 (m) 962 (m), 931
1

(m), 775 (m). H NMR (500 MHz, DMSO-d6, ppm): 1.39 (t, (t, J = 7.0 Hz, 3H, NCH2CH3), 1.46
(t, (t, J = 7.0 Hz, 3H, NCH2CH3), 3.66 (d, J = 18.0 Hz, 1H, PhCH2N), 3.71 (d, J = 18.0 Hz, 1H,
PhCH2N), 4.04 (dq, J1 = 14.0 Hz, J2 = 7.0 Hz, 1H, NCH2CH3), 4.08 (dq, J1 = 14.0 Hz, J2 = 7.0
Hz, 1H, NCH2CH3), 4.25 (dq, J1 = 14.0 Hz, J2 = 7.0 Hz, 1H, NCH2CH3), 4.57 (dq, J1 = 14.0 Hz,
J2 = 7.0 Hz, 1H, NCH2CH3), 4.64 (d, J = 15.0 Hz, 1H, NCH2CO), 4.96 (d, J = 15.0 Hz, 1H,
NCH2CO), 5.47 (d, J = 12.5 Hz, 1H, NCH2CO), 5.59 (d, J = 12.5 Hz, 1H, NCH2CO), 6.75-7.57

13

(m, 9H, aromat. H). C NMR (DMSO-d6, ppm): 13.95, 14.02 (NCH2CH3), 48.46, 48.71
(NCH2CH3), 61.69 (PhCH2N), 68.09, 68.82 (NCH2CO), 125.46, 126.73, 127.79, 129.07,
130.85, 131.47, 132.22, 134.08, 135.88(Caromat.), 152.79 (Caromat.-N), 167.64 (C=N), 173.20,
(C=O), 175.00 (C=O), 182.38 (C=S). +ESI MS (CH2Cl2): 657.1 (45% base peak, [M+H]+);
+

+

679.1 (100% base peak, [M+Na] ); 695.2 (80% base peak, [M+K] ).

4.3.6. [Re(NPh)(L)] (5)
H3L (0.1 mmol) and 3 drops of Et3N were added to a stirred suspension of [Re(NPh)Cl3(PPh3)2] (90 mg, 0.1 mmol) in 5 mL of CH2Cl2. The reaction mixture was heated on
reflux for 1 hour. During this time, the precursor complex completely dissolved and a clear

17


yellow-green solution was obtained. The solvent was removed under vacuum and the
residue was purified by column chromatography on silica with a CHCl3/n-hexane mixture
(1:1, v/v) as mobile phase.
[Re(NPh)(LMorph)] (5Morph): Yield 40% (29.0 mg). Elemental analysis: Calcd. for
C29H28N5O5ReS: C, 46.7; H, 3.8; N, 9.4; S, 4.3%. Found: C, 46.5; H, 3.6; N, 9.2; S, 4.5%. IR
-

(KBr, cm 1): 3060 (w), 2990 (w), 2900 (w), 2858 (w), 1701 (vs), 1508 (s), 1481 (s), 1435 (s),
1342 (m), 1299 (m), 1261 (m), 1219 (m), 1110 (m), 1022 (m), 914 (w), 899 (w), 806 (m),
771 (m), 732 (w), 682 (w), 528 (w). 1H NMR (400 MHz, CDCl3, ppm): 3.48 (d, J = 17.1 Hz,
1H, PhCH2N), 3.73 (d, J = 17.1 Hz, 1H, PhCH2N), 3.89 (m, 4H, NCH2), 4.23 (d, J = 14.6 Hz,

1H, CH2CO), 4.30 (m, 2H, OCH2), 4.49 (m, 2H, OCH2), 4.82 (d, J = 14.6 Hz, 1H, CH2CO),
5.03 (d, J = 12.1 Hz, 1H, CH2CO), 5.27 (d,

J = 12.1 Hz, 1H, CH2CO), 6.65-7.47 (m, 14H,

13

aromat. H). C NMR (CDCl3, ppm): 49.61, 49,83 (NCH2), 61.85 (PhCH2N), 66.53, 66.79
(OCH2), 69.67, 69.99 (NCH2CO), 122.16, 124.22, 124.37, 128.24, 128.63, 128.67, 130.11,
130.99, 131.28, 131.45, 132.90, 136.76(Caromat.), 152.62 (Caromat.-N), 156.34 (Caromat.-N=Re),
166.85 (C=N), 174.39, (C=O), 176.97 (C=O), 181.88 (C=S). +ESI MS (CH2Cl2): 746.1
(100% base peak, [M+H]+); 768.2 (70% base peak, [M+Na]+).

4.4. X-Ray Crystallography
The intensities for the X-ray determinations were collected on a STOE IPDS 2T instrument
with Mo Kα radiation (λ = 0.71073 Å). Standard procedures were applied for data reduction and absorption correction. Structure solution and refinement were performed with
SHELXS97 and SHELXL97 [31]. Hydrogen atom positions were calculated for idealized
positions and treated with the ‘riding model’ option of SHELXL. More details on data
collections and structure calculations are contained in Table 4.

18


Table 4. X-ray structure data collection and refinement parameters
[ReO(LMorph)]

[Re(NPh)(LMorph)]

Formula

C23H23N4O6ReS

C29H28N5O5ReS

Mw

669.71

744.82

Crystal system

Monoclinic

Orthorhombic

a/ Å

9.562(1)

7.813(1)

b/ Å

22.684(1)

8.565(1)

c/ Å

0.620(1)

40.864(3)

α/o

90

90

β/

94.25(1)

90

γ/o

90

90

V/ Å3

2297.4(3)

2734.3(4)

Space group

P21/n

P 212121

Z

4

4

1.936

1.809

µ/mm

5.429

4.571

No. of reflections

13961

14880

No. of independent

4871

6831

Rint

0.0936

0.0997

No. parameters

317

371

R1/wR2

0.0439 / 0.0834

0.0515 / 0.1122

GOF

1.003

0.882

o

-3

Dcalc./g cm
-1

Flack parameter

-0.030(18)

4.5. Computational details
Et

Et

The gas phase geometries of [ReO(L )] and [ReO(L* )] were optimized without any
symmetry restrictions in singlet ground states by the DFT method with two different
exchange correlation functional approaches, PBE1PBE and B3LYP, using the Gaussian-09
Revision D.01 program package [18]. For the complex [ReO(L* Et)], the initial geometry

19


used for the optimization is based on crystal structure parameters [14]. Regarding to the
Et

Et

complex [ReO(L )], the initial geometry is derived from crystal structure of [ReO(L* )]
with modification of position of CH2 group, and because the single crystal suitable for Xray structure analysis was not available, the significant bond lengths and angles of the
optimized geometry are compared with the crystal structure of 4Morph. The employed basis
set combinations are found in Table 1. The basis set LANL2TZ for Re was obtained from
the EMSL Basis Set Library [33,34]. The optimized geometries were verified by

performing frequency calculations. The absence of an imaginary frequency ensures that the
optimized geometries correspond to true energy minima. Energy values for both complexes
were corrected by Zero Point Energy (ZPE). All theoretical calculations were carried out
with the high-performance computing system of ZEDAT, Freie Universität Berlin,
( ).

Acknowledgements
We gratefully acknowledge financial support from DAAD (Deutscher Akademischer
Austauschdienst, Germany).

Appendix A. Supplementary data
CCDC-1400143 and CCDC-1400144 contain the supplementary crystallographic
data for [ReO(LMorph)] and [Re(NPh)(LMorph)], respectively. These data can be obtained free
of charge via or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223336-033; or e-mail:

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23


Figure Captions

Figure 1

Molecular structure of [ReO(LMorph)] (4 Morph) [32]. Hydrogen atoms are
omitted for clarity.

Figure 2

Molecular structure of [Re(NPh)(LMorph)] (5Morph) [32]. Hydrogen atoms are
omitted for clarity.

24