[Re(η6-C6H5-benzimidazole)2]+ and Derivatives as Dye Mimics; Synthesis, UV Absorption Studies and DFT Calculations

Article abstract of DOI:10.1002/ejic.202100294

Functionalizations of highly oxidation and hydrolysis stable mono-cationic rhenium bis-arene complexes [Re(η⁶-C₆H₆)₂]⁺ are of great interest. We directly built up structural features of the well-known Hoechst Dye on the coordinated arenes as a model for prospective DNA minor groove binding studies. Extensions of the aromatic bis-arene unit with functionalized and derivatized benzimidazole moieties resulted in a deep orange colour of the complexes, showing UV/Vis absorption spectra with multiple transition maxima. These have been assigned with support of DFT calculations to gain information about their charge transfer natures. The different transitions of the complexes, which are either intra-ligand, ligand-to-ligand or metal-to-ligand charge transitions, were additionally compared and discussed with the spectra of the corresponding free ligands.

Full text of DOI:10.1002/ejic.202100294

European Journal of Inorganic Chemistry
Accepted Article
Title: [Re(h6-C6H5-benzimidazole)2]+ and Derivatives as Dye Mimics;
Syntheses, UV Absorption Studies and DFT Calculations
Authors: Carla Gotzmann, Olivier Blacque, Thomas Fox, and Roger
Alberto
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To be cited as: Eur. J. Inorg. Chem. 10.1002/ejic.202100294
Link to VoR: https://doi.org/10.1002/ejic.202100294
01/2020

10.1002/ejic.202100294
European Journal of Inorganic Chemistry
FULL PAPER
[Re(η6-C6H5-benzimidazole)2]+ and Derivatives as Dye Mimics;
Syntheses, UV Absorption Studies and DFT Calculations
Carla Gotzmann[a], Olivier Blacque[a], Thomas Fox[a] and Roger Alberto*[a]
[a]
Dr. Carla Gotzmann, Dr. Olivier Blacque, Dr. Thomas Fox, Prof. Dr. Roger Alberto
Department of Chemistry
University of Zurich
Winterthurerstrasse 190, 8057 Zurich, Switzerland
E-mail: ariel@chem.uzh.ch
Supporting information for this article is given via a link at the end of the document
Abstract: Functionalizations of highly oxidation and hydrolysis stable
mono-cationic rhenium bis-arene complexes ([Re(η6-C6H6)2]+; are of
great interest. We directly built up structural features of the well-known
Hoechst Dye on the coordinated arenes as a model for prospective
DNA minor groove binding studies. Extensions of the aromatic bis-
arene unit with functionalized and derivatized benzimidazole moieties
resulted in a deep orange colour of the complexes, showing UV/Vis
absorption spectra with multiple transition maxima. These have been
assigned with support of DFT calculations to gain information about
their charge transfer natures. The different transitions of the
complexes, which are either intra-ligand, ligand-to-ligand or metal-to-
ligand charge transitions, were additionally compared and discussed
with the spectra of the corresponding free ligands.
radionuclide therapy (186/188Re) and imaging (99mTc). Since some
time, we focus on the chemistry of highly stable, oxidation
insensitive rhenium bis-arene type complexes (e.g. [Re(η6-
C6H6)2]+ (1+), Scheme 1).[6c, 6d] The rationale behind is the option
of coordinating either of the two elements directly to phenyl
groups integrated in pharmaceuticals, without the need of a
bifunctional chelator. Whereas the direct synthesis of [99mTc(η6-
arene)2]+ complexes with highly functionalized arenes was
recently reported,[8] the preparation of rhenium homologues does
not work along this path. Functional modifications have to be
introduced after the preparation of the basic [Re(η6-arene)2]+
complex. Previously, we modified a procedure by Kudinov et al.[9]
and introduced basic functionalities to the coordinated arenes to
yield e.g. the mono- and bis-substituted benzoic acid complexes
[Re(η6-C6H5-COOH)( η6-C6H6)]+ (2+) and [Re(η6-C6H5-COOH)2]+
(3+) (Scheme 1).[6d]
Introduction
O
O
Bioorganometallic complexes have gained strong interest over
the past decades. They are employed for biological and medicinal
purposes but also in related fields such as environmental science,
toxicology, metallomics, energy, catalysis, biosensing,
radiopharmacy and as active sites in artificial and natural
metalloenzymes.[1] Metallocenes such as ferrocene, probably the
most important bioorganometallic compound, pioneered the field.
They are generally neutral, water- and air-stable to a certain
extent and can be derivatized or functionalized in numerous
ways.[1f],[2] Recently, structurally and electronically related
transition metal bis-arene complexes with isoelectronic, neutral
and aromatic cyclic π-aromatic hydrocarbons attracted attention.
Complexes comprising the [Ru(η6-cymene)]2+ substructure are
OH
OH
O
(i)
(ii)
+
Re
Re
Na[ReO4]
Re
OH
2+
3+
1+
Scheme 1. Reaction pathway to obtain [Re(η6-C6H5-COOH)(η6-C6H6)]+ (2+) and
[Re(η6-C6H5-COOH)2]+ (3+) starting from Na[ReO4].[6d]
(i) Zn powder, AlCl3, C6H6, 80°C reflux, 19h. (ii) LDA, dry THF, -78°C, 1.5 h; then
CO2-gas, -78°C, 3 h; H2O/TFA (4:1).
Complexes 2+ and 3+ are excellent starting materials for further
derivatizations, e.g. the coupling of biologically active molecules
via peptide bond formation. Pursuing this strategy for
derivatizations of 1+ with bio-relevant moieties, the backbone of
the prominent DNA minor groove binder Hoechst Dyes was
chosen as a target.[10] In general, a Hoechst Dye molecule
consists of a head-to-tail bound bis-benzimidazole moiety, which
additionally contains a methylpiperazine unit on the tail end and a
functionalized phenyl ring on the head end.[11],[12] In a first step,
the relevant DNA-binding parts of the Hoechst Dyes were
included to obtain a rhenium bis-arene complex bearing a minor
groove binding moiety for potential DNA-complex binding
(Scheme 2).
3]
core compounds in bioorganometallic cancer therapy.[1a,
Sandwich complexes of the bis-arene type [M(η6-arene)2]n+ are
isoelectronic to many metallocenes and only little studied in the
bioorganometallic field. Although existing for groups 6 (n=0) and
8 (n=2) in particular, they show lower kinetic and thermodynamic
stabilities than their mono-arene or cyclopentadienyl analogues.[4]
Synthetically, their preparations are not routine although
established e.g. along the Fischer-Hafner procedure since a long
time.[5] These bis-arene complexes are closed-shell complexes.[6]
They have been reviewed several times over the past years,
underlying their importance especially in catalysis but also for the
life sciences.[4a, 7]
Amongst the bis-arene complexes of the middle transition
elements, the ones of the manganese triad found probably the
least attention. Rhenium and 99mTc are of central interest in
1
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10.1002/ejic.202100294
European Journal of Inorganic Chemistry
FULL PAPER
Complexes [4](OTf) and [5](OTf) were obtained as orange solids
in moderate yields (38% and 24%) after prep. HPLC separation.
The compounds with triflate (OTf-) counter-ions are very well
soluble in water, methanol and ethanol whereas complexes with
PF6– are well soluble in non-protic solvents (dichloromethane,
ethyl acetate). NMR spectra and HR-ESI-MS(+) confirmed the
nature of the complexes (see supporting information). Orange
single crystals for X-ray diffraction analysis could be obtained by
slow evaporation of a methanol solution of [4](PF6) or of [5](OTf).
An ORTEP is shown in Figure 1. The Re-C bond lengths to the
arene ligands of 4+ are within a normal range of 2.230(2)-
N
X
N
N
Re
H
N
H
Re
R
N
N
N
N
HN
N
H
Scheme 2. Introduction of the DNA Binding part of the Hoechst Dye (red) to the
rhenium bis-arene complex.
Only few studies of metal-bound Hoechst dyes are reported in
literature. In both cases, a metal-containing part such as a metal-
porphyrin[13] (M = Ni, Mn) or a ruthenium phosphorescent
complex[14] was coupled to a Hoechst Dye molecule via a linker
and DNA binding studies have been carried out.
2.2606(19) Å and are comparable to other rhenium bis-arene type
6d]
crystal structures.[6c,
In these and other X-ray structure
analyses, the compounds show in the crystal packing extensive
intermolecular π-π-stacking interactions, in general between the
benzimidazole moieties and one of the coordinated arenes. Such
a behavior implies the possibility of a π-stacking into DNA as
expected for a Hoechst-dye like compound.
To the best of our knowledge, no direct rhenium-bound Hoechst
dye has been reported. DNA binding studies with a rhenium-
bound Hoechst dye would allow assessing the binding mode of
the complex to the DNA minor groove. From the cationic charge
of the bis-arene complex, one might expect a higher binding
constant than with neutral ones.
In this report, we present derivatizations with one and two
benzimidazole units on 2+ and 3+ respectively, to aim a metal
containing DNA minor-groove binding complexes, including
adapted synthetic routes for all intermediates, full characterization
and crystal structures. Furthermore, UV/Vis studies as well as
corresponding time-dependent DFT calculations have been
carried out to gain deeper insights into the photophysics of these
colorful aromatic transition metal complexes.
Figure 1. Ellipsoid displacement representation of [Re(η6-C6H5-BzI)(η6-C6H6)]+
cation in the [4](PF6) structure. Hydrogen atoms, H2O and counter-ion are
omitted for clarity; displacement ellipsoids are represented at the 50%
probability level. Selected bond lengths [Å]: Re1-C1 2.249(2), Re1-C2 2.253(2),
Re1-C3 2.243(2), Re1-C4 2.232(2), Re1-C5 2.234(2), Re1-C6 2.244(2), Re1-
C7 2.2606(19), Re1-C8 2.243(2), Re1-C9 2.234(2), Re1-C10 2.238(2), Re1-
C11 2.230(2), Re1-C12 2.238(2), C7-C13 1.471(3), C13-N1 1.346(3), C13-N2
1.336(3).
Results and Discussion
Complex Syntheses. Simple amide bond formations of 2+ and 3+
with benzyl amine have been reported by our group[6d]. The
benzimidazole moieties (BzI) on one or both of the coordinated
benzene rings were obtained by reacting 2+ and/or 3+ with ortho-
phenylenediamine via prevalent amide bond formation with
activation agents such as HOBt, EDCI and DIPEA in DMF. A
semi-stable mono-amide intermediate was obtained, which was
isolated by preparative high-performance liquid chromatography
(prep. HPLC). This intermediate "decomposed" quickly in acidic
solvent media back to the starting complexes 2+ and 3+
respectively. If the reaction mixture was directly quenched with
aqueous trifluoroacetic acid (TFA, 4:1, pH=1) and heated to 60-
80°C overnight, an intramolecular condensation reaction (Phillips-
Condensation[15]) took place which resulted in the BzI derivatised
rhenium complexes [Re(η6-C6H5-BzI)(η6-C6H6)]+ (4+) and [Re(η6-
C6H5-BzI)2]+ (5+) (Scheme 3).
For further extending the once coupled benzimidazole system,
towards a Hoechst-like system, differently functionalized 1,2-
phenylenediamines were reacted with 2+ and 3+ to obtain the
bromide- and ester-functionalized complex cations 6+ to 9+
(Scheme 4). The reaction procedures are similar to the one
described for 4+ and 5+ including amide bond formation in a first
step, followed by an internal condensation reaction. These steps
led clearly to the bromo- and ester functionalized benzimidazole
rhenium complexes 6+ - 9+.
NH2
O
O
N
H2N
H2N
OH
HN
(i)
(ii)
N
H
+
Re
Re
Re
R1, R2
R1, R3
NH2
R1, R4
4+: R1 , 5+: R4
2+: R1, 3+: R2
O
N
O
R
1 = H
R2
=
R3
=
R4
=
HN
OH
N
H
Scheme 3. Reaction pathways from [Re(η6-C6H6)2]+ (1+) to the benzimidazole
derivatised analogues [Re(η6-C6H5-BzI)(η6-C6H6)]+ (4+) and [Re(η6-C6H5-BzI)2]+
(5+). (BzI = benzimidazole) a
(i) HOBt, EDCI, DIPEA, DMF, r.t., 16 h. (ii) H2O/TFA (4:1), 60°C, 16h.
2
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10.1002/ejic.202100294
European Journal of Inorganic Chemistry
FULL PAPER
COOH
H2N
H2N
H2N
H2N
COOEt
COOEt
H2N
Br
Br
N
(iii)
(i,ii)
N
H
H2N
Re
(i)-(ii)
H2N
O
O
R1,R3
H
N
OH
6+: R1 ; 7+: R3
N
N
H
Re
L1
L2
L3
R1,R2
COOEt
N
N
(iv)
H
H
N
(i)-(ii)
2+: R1 ; 3+: R2
COOH
COOEt
H
N
N
Re
(v)
H2N
H2N
COOEt
R1,R4
N
L4
8+: R1 ; 9+: R4
(vi,vii)
HN
N
COOEt
Br
H
N
O
N
N
R1 = H
R2
=
R4
=
R3
=
OH
N
N
H
N
H
L5
Scheme 4. Reaction pathways towards functionalized benzimidazole:
Scheme 6: Synthetic procedure to obtain the corresponding ligands; (i) HOBt,
EDCI, DIPEA, dry DMF, r.t., 3h. (ii) H2O/TFA (pH=1), 50°C, 15h. (iii) HOBt, EDCI,
DIPEA, DMF, r.t., 24h. (iv) m-xylene/ glacial acetic acid (13:1), 80°C, 6h. (v)
KOH, MeOH, r.t. 18h. (vi) 1,2-phenylenediamine, HOBt, EDCI, DIPEA, dry DMF,
r.t., 16h. (vii) H2O/TFA (pH=1), 60°C, 17h.
(i) HOBt, EDCI, DIPEA, DMF, r.t., 19-25 h. (ii) H2O/TFA (pH=1), 50-60°C, 19-22
h.
Complexes 6+-9+ are of orange color, which are for the bis-
functionalized complexes 7+ and 9+ stronger than for the mono-
functionalized complexes 6+ and 8+.
Towards Hoechst dyes, the bromide substituents in 6+ and 7+
make them susceptible for nucleophilic aromatic substitution
reactions. Ester-functionalized complexes 8+ and 9+ were
hydrolyzed with potassium hydroxide to the corresponding
carboxylates 10+ and 11+ (Scheme 5).
With the exception of L3, all ligands are described in the
literature.[16] Applying the synthetic route in analogy to the
rhenium complexes, these ligands could be synthesized in easier
and faster procedures with good yields and a more facile
purification. All ligands were fully characterized to complete the
analytical data and obtain corresponding spectra for the
comparison with those of the rhenium complexes.
N
N
N
H
UV Absorption Studies. Electronic spectra of bis-arene rhenium
N
H
O
O
N
complexes are scarce and UV/Vis data are only available for 1+
Re
N
OH
O
(iii)-(iv)
6d]
and a few aniline-type complexes.[6c,
The brightness of the
N
N
(i)-(ii)
12+
H
H
Re
Re
R1,R2
R1,R3
compound colors encouraged us to investigate their electronic
spectra.
O
O
8+ = R1, 9+ = R2
10+ = R1, 11+ = R3
N
N
NH
O
O
Re
H
N
All rhenium bis-arene complexes are yellow to dark orange in
color while the ligands appear off-white. To obtain a deeper
insight into the features of the observed electronic transitions in
1+, the mono-substituted complexes 4+, 8+ and 12+ as well as the
di-substituted rhenium complexes 5+ and 9+, we analyzed the
spectral maxima by TD-DFT calculations to assign the respective
transitions. The participating orbitals for compounds 1+, 4+, 5+, 8+,
9+, 12+ and the corresponding neutral ligands L1, L3 and L5 are
given in the supplementary information figures S81-89.
Additionally the three ligands L1, L3 and L5 were investigated as
well for comparison.
Figure 2 pictures the absorption spectra of L1 (black), L3 (red),
and L5 (blue). Three different main absorption bands are distinct.
The higher energy band between 200-235 nm mainly describes
π→π* intra-ligand charge transfers (1ILCT) amongst the
benzimidazole or the phenyl ring. Ligand-to-ligand charge transfer
(1LLCT) between an occupied π-benzimidazole and an
unoccupied π*-phenyl orbital is shown in the second maximum
(235-265 nm). These first two maxima are in a similar range for
all three ligands, differing only in the molar extinction values ε. The
third maximum, a 1ILCT (πligand→π*ligand) delocalized over the whole
molecule, is in a range of 265-330 nm for L1 and L3 implicating
small changes in the molecular structure. The maximum of L5 is
shifted to higher wavelengths (320-375 nm) confirming its
structural difference due to the second sequenced benzimidazole
moiety.
N
H
N
N
OH
R3
=
O
R1 = H R2
=
N
H
N
N
13+
H
H
Scheme 5. Introduction of a second benzimidazole Unit; (i) KOH, H2O, r.t. 15-
18h. (ii) H2O/TFA (pH=1). (iii) o-phenylenediamine, HOBt, EDCI, DIPEA, DMF,
r.t., 20h. (iv) H2O/TFA (pH=1), 60°C, 16h.
Reacting 10+ with another 1,2-phenylene-diamine moiety gave
complex 12+ with two sequenced benzimidazole moieties. This
complex is the closest mimic to the Hoechst dyes. Its authenticity
was confirmed with NMR and HR-ESI-MS(+) spectroscopy (see
supporting information). The synthesis of 11+ with 1,2-
phenylenediamine to obtain a complex with two BzI-BzI moieties
attached to both arene rings lead within a short reaction time to a
complex with the two acid functionalities bridged by amide bonds
and the formation of 13+. This compound is the kinetically favored
product in the reaction as the distance of the two acid functions
has been close enough to be bridged by a 1,2-diaminobenzene
molecule. The color of the compound was slightly lighter orange
compared to 12+, which is also confirmed in the absorption
spectra. All bands are in a very similar wavelength range as found
in 11+ and only differ in the epsilon values. Additionally, extensive
NMR spectroscopy and HR-ESI-MS(+) confirmed the structure of
13+ (see supplementary information).
Ligand Syntheses. The pure arene-benzimidazole ligands were
prepared separately for later comparison of spectroscopic data
with those of the respective complexes. (Scheme 6).
3
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10.1002/ejic.202100294
European Journal of Inorganic Chemistry
FULL PAPER
Figure 4. UV absorption spectra of 12+ (black) and the corresponding ligand L5
Figure 2. UV absorption spectra of the ligands L1 (black), L3 (red), L5 (blue);
(red); in methanol at room temperature.
in methanol at room temperature.
The two remaining maxima of 12+ are attributed to transitions
involving metal orbitals. Between 270-290 nm, electron transition
is executed from the dmetal orbitals (HOMO) into the π*-orbitals
(LUMO) of the phenyl rings. The low energy HOMO-LUMO
transition occurs between dmetal and π*ligand orbitals.
A comparison of the absorption spectra of 1+ and the mono-
derivatised complexes 4+, 8+ and 12+ is shown in Figure 3. Beside
1+ (black line), which displays a single band with a maximum at
265 nm indicating
a
metal-to-ligand charge transfer
(dmetal→π*phenyl) between the rhenium atom and the coordinated
phenyl rings, all other complexes show at least five different
transitions. The spectral characteristics of 4+ and 8+ are very
similar and confirm that the ester moieties do not influence on the
rest of the complex structures. Above 330 nm, the two maxima of
12+ are shifted to higher wavelengths as compared to 4+ and 8+.
Figure 5. UV absorption spectra of 8+ (black) and 9+ (red), in methanol at room
temperature.
Figure 5 contrasts the absorption spectra of the mono-substituted
complex 8+ with the di-substituted complex 9+. It is noticeable that
the molar extinction values for the di-substituted complex 9+ is
roughly twice as much as the ones for 8+. All maxima can be found
in the same wavelength range beside the intra-ligand transitions
between 290-350 nm. These are more pronounced for 8+ with two
peaks, while 9+ shows a broad maximum in this range. The lower
energy 1MLCT maximum is also shifted to higher wavelengths for
9+ (around 390 nm) compared to 8+ at around 375 nm. The
complexes show weak fluorescence with emission maxima
between 360 - 390 nm.
Figure 3. UV absorption spectra of 1+ (black), 4+ (red), 8+ (blue) and 12+ (green);
in methanol at room temperature.
1
1
The π→π* ILCT transitions (210-235 nm) and LLCT (235-260
nm) are the same as described for the corresponding ligands. In
the range of 260-280 nm, all complexes show a 1MLCT between
occupied rhenium metal d-orbitals (HOMO) and unoccupied
phenyl π*-orbitals (LUMO). Another 1ILCT transition (π→π*) is
pictured between 280-360 nm, which is again of pure ligand
character, delocalized over the entire molecule without any metal
contribution. The lowest energy transition (360-400 nm, except 1+)
Conclusion
1
is described as another MLCT between the HOMO (dmetal) and
the LUMO (π*), distributed over the whole ligand.
We showed in this study that systematic derivatizations of the
basic [Re(η6-C6H6)2]+ are feasible even with relatively complex
functionalities such as the Hoechst Dye. The bio-relevant
conjugated benzimidazole dyes did not affect properties such as
inertness or water solubility of the rhenium scaffold. Beside
synthesis and characterization, detailed UV-Vis studies have
Figure 4 displays the absorption spectra of complex 12+ (black)
and ligand L5 (red, dashed line). This comparison verifies that
three maxima are defined as 1ILCT and 1LLCT HOMO-LUMO
transitions (π→π*) without any metal orbital influence.
4
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10.1002/ejic.202100294
European Journal of Inorganic Chemistry
FULL PAPER
water (with TFA, pH 1) and the reaction mixture was heated to 50°C for
19 h. The reaction was allowed to cool to r.t., the solvent was evaporated
and the crude product was purified by prep. HPLC (Gradient: prep. HPLC
2). The product containing fractions were combined and the solvent was
evaporated to yield [8](TFA) as an orange solid. Yield: 40.8 mg
(0.064 mmol, 49%).
allowed obtaining deeper insights about the photophysical
properties, which could be assigned by time-dependent DFT
calculations. All compounds show at least three different ILCT or
LLCT transitions together with two MLCT transitions
(dmetal→π*phenyl and dmetal→π*ligand, respectively). These first results
for metal bis-arene complexes are employed for conjugating the
[Re(η6-arene)2]+ core to further photoactive compounds, such as
photosensitizers. Corresponding biological investigations are
currently performed. Preliminary DNA binding studies indicate an
interaction between 12+ and the DNA minor groove. These
interactions are currently investigated and elaborated in more
detail.
Analysis of [8]+: 1H NMR (500 MHz, CH3OD): δ [ppm] = 8.31 (s, 1H, H6),
8.01 (dd, 1H, H5), 7.67 (dd, 1H, H4), 6.99 (d, 2H, H1), 6.38 (t, 2H, H2), 6.23
(t, 1H, H3), 6.06 (s, 6H, H9), 4.39 (q, 2H, H7), 1.42 (t, 3H, H8). 13C NMR
(125 MHz, CH3OD): δ [ppm] = 168.28 (Cf), 153.56 (Cb), 143.05 (Cd),
140.45 (Cc), 127.26 (Ce), 126.15 (C5), 119.04 (C6), 115.98 (C4), 81.77 (Ca),
80.66 (C9), 77.43 (C3), 77.21 (C2), 76.47 (C1), 62.44 (C7), 14.80 (C8). IR
(neat): ν [cm-1]: 3075 (m), 2981 (w), 1782 (w), 1671 (s), 1630 (w), 1512 (w),
1471 (w), 1433 (s), 1416 (w), 1394 (w), 1367 (m), 1320 (w), 1299 (s), 1197
(s), 1176 (m), 1116 (s), 1088 (w), 1023 (s), 950 (s), 888 (w), 854 (w), 831
(s), 797 (s), 768 (m), 742 (s), 717 (s), 703 (w). HR-ESI-MS (MeOH):
Experimental Section
C
22H20O2N2Re [M]+: calculated, 531.10768; found, 531.10814. UV/Vis
(MeOH): ε369 = 2803 M-1cm-1; ε331 = 8190 M-1cm-1; ε303 = 13607 M-1cm-1;
ε272 = 18093 M-1cm-1; ε247 = 16427 M-1cm-1; ε216 = 25637 M-1cm-1.
General Information. Experimental methods, synthetic procedures,
analytical data and NMR assignments are described in the Supporting
Information for all compounds. In this section only the procedures of the
key compounds [4](TFA), [5](TFA), [8](TFA), [10](OTf) and [12](TFA) are
given. Complexes [1](OTF), [2](TFA) and [3](TFA) were synthesised
according to literature.[6d]
[Re(η6-C6H5-BzI-BzI)(η6-C6H6)](TFA) [12](TFA). [10](OTf) (50.0 mg,
0.077 mmol, 1.0 eq.) was dissolved in DMF before 1,2-phenylenediamine
(14.9 mg, 0.138 mmol, 1.8 eq.) and HOBt (33.4 mg, 0.247 mmol, 3.2 eq.)
were added under N2. After 10 min of stirring, EDCI (44.5 mg, 0.232 mmol,
3.0 eq.) and DIPEA (79 µl, 60.0 mg, 0.463 mmol, 6.0 eq.) were added and
the reaction mixture was stirred at r.t. for 20 h before evaporating the
solvent. The orange residue was taken up in acidified H2O (with TFA; 20:1)
and heated for 16 h at 60°C. The reaction mixture was allowed to cool to
r.t., the solvent was evaporated and the crude mixture was purified by prep.
HPLC (Gradient: prep. HPLC 3). Pure product containing fractions were
combined and the solvent was evaporated to afford [12](TFA) as an
orange solid. Yield: 10.1 mg (0.015 mmol, 19%)
[Re(η6-C6H5-BzI)(η6-C6H6)](TFA)
([4](TFA))
and
[Re(η6-C6H5-
BzI)2](TFA) ([5](TFA)). A flask was charged with [3](TFA) (58.2 mg,
0.107 mmol, 1 eq.), 1,2-phenylenediamine (35.3 mg, 0.327 mmol, 3.1 eq.),
HOBt (120.1 mg, 0.890 mmol, 8.3 eq.) and DMF (10 ml) under N2. After
5 min of stirring, EDCI (164.9 mg, 0.860 mmol, 8.0 eq.) and DIPEA (220 µl,
167.2 mg, 1.289 mmol, 12.0 eq.) were added and the reaction mixture was
stirred at r.t. for 16 h before evaporating the solvent. The residue was
redissolved, acidified in H2O/ TFA (10:1) and heated to 60°C for 16 h. The
solvent was removed and the crude product was purified by prep. HPLC
(Gradient: prep. HPLC 1, see Supporting Infomation). The product
containing fractions were combined and the solvent was evaporated to
yield [4](TFA) and [5](TFA) as orange solids. Yields: 23.4 mg (0.041 mmol,
38%) for [4](TFA) and 17.6 mg (0.026 mmol, 24%) for [5](TFA).
Analysis of 12+: 1H NMR (500 MHz, CH3OD): δ [ppm] = 8.47 (dd, 1H, H7),
8.07 (dd, 1H, H6), 7.94 (dd, 1H, H5), 7.84 (m, 2H, H8/11), 7.64 (m, 2H, H9/10),
7.05 (d, 2H, H1), 6.41 (t, 2H, H2), 6.25 (t, 1H, H3), 6.09 (s, 6H, H4). 13C NMR
(125 MHz, CH3OD): δ [ppm] = 155.06 (Cb), 151.69 (Cf), 143.39 (Cd),
141.89 (Cc), 133.35 (Cg/h), 127.91 (C9/10), 124.18 (C6), 118.98 (Ce), 117.95
(C7), 117.75 (C5), 114.95 (C8/11), 81.39 (Ca), 80.76 (C4), 77.47 (C3), 77.31
(C2), 76.61 (C1). IR (neat): ν [cm-1]: 3067 (br), 2655 (w), 1664 (s), 1629 (m),
1575 (m), 1519 (m), 1455 (w), 1438 (w), 1421 (w), 1410 (w), 1395 (w),
1308 (m), 1271 (w), 1233 (w), 1180 (s), 1127 (s), 1006 (m), 947 (m), 923
(w), 899 (m), 829 (s), 796 (s), 753 (s), 719 (s). HR-ESI-MS (H2O):
Analysis of 4+: 1H NMR (500 MHz, CH3OD): δ [ppm] = 7.62 (m, 2H, H4),
7.33 (m, 2H, H5), 6.96 (d, 2H, H1), 6.37 (t, 2H, H2), 6.21 (t, 1H, H3), 6.04 (t,
1H, H6). 13C NMR (125 MHz, CH3OD): δ [ppm] = 150.69 (Cb), 140.17 (Cc),
125.19 (C5), 116.49 (C4), 82.67 (Ca), 80.46 (C6), 77.51 (C3), 77.18 (C2),
76.37 (C1). IR (neat): ν [cm-1]: 3078 (br), 1623 (m), 1510 (w), 1429 (s),
1362 (w), 1316 (m), 1279 (m), 1232 (w), 1151 (w), 1106 (w), 824 (s), 767
C
26H20N4Re [M]+: calculated, 575.12406; found 575.12426. UV/Vis
(MeOH): ε374 =9163 M-1cm-1; ε341 = 20627 M-1cm-1; ε321 = 18160 M-1cm-1;
ε
275 = 22430 M-1cm-1; ε243 = 18850 M-1cm-1; ε219 = 30370 M-1cm-1.
(m), 751 (s). HR-ESI-MS (MeOH):
459.08655; found, 459.08644. UV/Vis (MeOH): ε370 = 1484 M-1cm-1; ε331
C
19H16N2Re [M]+; calculated,
=
4142 M-1cm-1; ε299 = 7720 M-1cm-1; ε270 = 8340 M-1cm-1; ε233 = 4376 M-1cm-
1; ε203 = 20394 M-1cm-1.
Acknowledgements
Analysis of 5+: 1H NMR (500 MHz, CH3OD): δ [ppm] = 7.11 (m, 8H, H4,5),
6.91 (d, 4H, H1), 6.46 (t, 4H, H2), 6.24 (t, 2H, H3). 13C NMR (125 MHz,
CH3OD): δ [ppm] = 148.06 (Cb), 139.25 (Cc), 125.10 (C5), 116.09 (C4),
84.50 (Ca), 79.42 (C2), 79.10 (C3), 77.87 (C1). IR (neat): ν [cm-1]: 3076 (m),
2968 (w), 2138 (w), 1685 (s), 1588 (w), 1557 (w), 1495 (w), 1448 (w), 1423
(s), 1362 (w), 1314 (s), 1272 (m), 1229 (w), 1198 (m), 1183 (m), 1131 (s),
1103 (w), 1003 (m), 949 (m), 838 (s), 807 (m), 768 (s) 746 (s), 720 (m).
HR-ESI-MS (MeOH): C26H20N4Re [M]+; calculated, 575.12406; found,
575.12402. UV/Vis (MeOH): ε382 = 5436 M-1cm-1; ε310 = 19748 M-1cm-1;
This study was financially supported by the University of Zurich.
Keywords: Sandwich Complexes, Bioorganometallic Chemistry,
Hoechst Dye, Rhenium
ε
275 = 21340 M-1cm-1; ε204 = 59928 M-1cm-1.
Conflict of Interest
[Re(η6-C6H5-BzI-COOEt)(η6-C6H6)](TFA) ([8](TFA)). A flask was charged
with [2](TFA) (63.3 mg, 0.127 mmol, 1 eq.), 3,4-diaminobenzoic acid ethyl
ester (38.3 mg, 0.213 mmol, 1.7 eq.), HOBt (52.4 mg, 0.388 mmol, 3 eq.)
and DMF (10 ml) under N2. After 5 min of stirring, EDCI (78.1 mg, 0.407
mmol, 3.2 eq.) and DIPEA (133 µl, 101.08 mg, 0.782 mmol, 6.2 eq.) were
added and the reaction mixture was stirred at r.t. for 24 h before
evaporating the solvent. The orange residue was redissolved in acidified
The authors declare no conflict of interest.
5
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10.1002/ejic.202100294
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Entry for the Table of Contents
Mono- and di-substituted positive-charged Rhenium-(η6-arene) complexes with different functionalized and derivatized benzimidazole
units have been synthesized and characterized. UV/Vis studies assisted by DFT calculations give deeper insights into the nature of
the absorptions of the complexes.
7
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