Synthesis, Characterization, and Catalytic Activity of Heteroleptic Rhodium Complex for C–N Couplings

Article abstract of DOI:10.1134/S1070328419010135

Abstract: We have reported synthesis of complex [Rh(COD)(L{Me})Cl] (III), where L{Me} (II) is N-(1-methylpyridin-4(1H)-ylidene)benzamide and COD is 1,5-cyclooctadiene. Monodentate ligand L{Me} was synthesized by deprotonation of [HL{Me}][OTf] (I) with sodium hydride. [HL{Me}][OTf] was synthesised by methylation of N-(pyridin-4-yl)benzamide (HL) with methyl triflate. All the three synthesized compounds were characterized by FT-IR, NMR (¹H and ¹³C), elemental and MS analyses. The structure of complex I was further explored with single crystal XRD and computational studies. Complex I was found as a good catalyst for C–N coupling reactions. Molecular docking revealed strong binding of rhodium complex with myoglobin.

Full text of DOI:10.1134/S1070328419010135

ISSN 1070-3284, Russian Journal of Coordination Chemistry, 2019, Vol. 45, No. 1, pp. 62–73. © Pleiades Publishing, Ltd., 2019.
Synthesis, Characterization, and Catalytic Activity of Heteroleptic
Rhodium Complex for C–N Couplings1
M. N. Zafara, *, Fouzia Perveenb, A. Naza, Ehsan Ullah Mughalc,
Gul-e-Sabad, and K. Hinac
aDepartment of Chemistry, Quaid-i-Azam University, Islamabad, 45320 Pakistan
bRCMS, National University of Science and Technology, Islamabad, 44000 Pakistan
cDepartment of Chemistry, University of Gujrat, Gujrat, 50700 Pakistan
dInstitute of Marine Biotechnology, University Malaysia, Terengganu, 21030 Malaysia
*e-mail: analyticalc@yahoo.com
Received January 9, 2018; revised April 23, 2018; accepted June 15, 2018
Abstract⎯We have reported synthesis of complex [Rh(COD)(L{Me})Cl] (III), where L{Me} (II) is N-(1-
methylpyridin-4(1H)-ylidene)benzamide and COD is 1,5-cyclooctadiene. Monodentate ligand L{Me} was
synthesized by deprotonation of [HL{Me}][OTf] (I) with sodium hydride. [HL{Me}][OTf] was synthesised
by methylation of N-(pyridin-4-yl)benzamide (HL) with methyl triflate. All the three synthesized com-
pounds were characterized by FT-IR, NMR (1H and 13C), elemental and MS analyses. The structure of com-
plex I was further explored with single crystal XRD and computational studies. Complex I was found as a
good catalyst for C–N coupling reactions. Molecular docking revealed strong binding of rhodium complex
with myoglobin.
Keywords: N-(1-alkylpyridin-4(1H)-ylidene)amide, rhodium heteroleptic complex, density functional the-
ory, molecular docking, myoglobin composites, C–N couplings
DOI: 10.1134/S1070328419010135
INTRODUCTION
class of neutral ligand such as N-(1-alkylpyridin-
4(1H)-ylidene) amide (PYA) with similar reso-
nance structures is recently reported [3]. It can
exist in three resonance forms are shown in
Owing to the high potential of N-heterocyclic
carbenes (NHCs) as ligands in homogenous catal-
ysis, the demand of ligands with similar structural
and electronic features is obvious [1, 2]. A new Scheme 1:
R1
R1
N+
R1
N+
N
O
O
−O
N
−N
N
R2
R2
R2
N-(1-alkylpyridin-4(1H)-ylidene)alkylinamide
Pyridinium amidate
o-Pyridinium amidate
Scheme 1.
1
The article is published in the original.
62

SYNTHESIS, CHARACTERIZATION, AND CATALYTIC ACTIVITY
63
Two with a negative charge associated with the
donor atom (nitrogen or oxygen) and positive charge
on pyridinium group. The third neutral resonance
form shows negative charge in π-conjugation with a
positively charged pyridinium group. It could have an
influence on metal complex formation similar to
NHCs as these ligands are less polar than anionic ami-
dates themselves. Considering the fact that amidates
are suitable for promoting oxidative addition reactions
with the late transition metals [4–10] and the neutral
nature of PYA can mimics metal–ligand equilibria of
metal-NHC and metal-phosphine catalytic cycles,
these ligands can be very powerful in homogenous
catalysis. Rh(I)-NHC complexes have been success-
fully utilized for C–N and other cross coupling reac-
tions [11–13]. Pd(II)-PYA complexes were utilized for
C–C cross coupling reactions in our initial work [3].
Being non-innocent ligand in nature, its complexes
with ruthenium such as Ru(η6-p-cymene)(PYA) and
Ir(η5-cp*))(PYA) showed (de)hydrogenation and
water oxidation catalysis, respectively [14–16].
In this current work, monodentate pyridinium
amidate, [L{Me}] (II), protonated pyridinium ami-
date, [HL{Me}][OTf] (I), as well as its rhodium com-
plex [Rh(COD)(L{Me})Cl] (III), were synthesized
and characterized. The structure of I was further
explored by single crystal XRD and density functional
theory (DFT) methods. It includes electronic proper-
ties, excitations, molecular electrostatic potential
(MEP), energies of chemical states and docking stud-
ies with myoglobin. It has been developed in several
studies that electronic and geometric properties calcu-
lated by DFT methods are far more reliable than semi-
empirical methods [36, 37]. Complex III was also uti-
lized as a catalyst for C–N coupling reactions owing to
low oxidation state of Rhodium bonded with electron
donor ligands.
EXPERIMENTAL
Materials and instrumentation. All reactions were
performed using standard Schlenk techniques and uti-
lized moisture free nitrogen environment unless oth-
erwise noted. Solvents and liquid reagents were dis-
tilled under nitrogen. Dichloromethane was dried
using a MBRAUN MB SPS-800 solvent purifier and
stored under nitrogen. Water was used deionized and
reagents were used as received. 4-Chloro-1-meth-
ylpyridin-1-ium triflate was prepared by our previous
reported method [38].
Composites of proteins and metal complexes are
attractive biomolecules as they act as sensors for bio-
markers [17, 18] and are artificial catalysts [19–21].
Various key biomarkers play an important role to pre-
dict disease susceptibility and assist in its manage-
ment. Myoglobin is an important cardiac biomarker
that is released into the bloodstream after induction of
muscle injury within 1 h and reaches its peak levels
after 2 h and thus an early indicator of acute myocar-
dial infarction [22, 23]. It can be monitored by quick
spectroscopic test of blood sample after addition of
organometallic precursor that can strongly interact
with this protein [24–26]. The other aspect of incor-
poration of catalytically active metal complexes in
well-characterized stable proteins is with respect to the
Infrared spectra were recorded over the range
4000–400 cm–1 on a Perkin Elmer Spectrum 400 FT-
IR spectrometer. NMR spectra were obtained using a
Bruker Avance spectrometer at 300 MHz (1H) and
preparation of artificial metalloenzymes having non- 75 MHz (13C) at 300 K at 298K. 1H spectra were refer-
natural functions [27–31]. The resulting hybrid cata-
lysts combine attractive features of both homogeneous
and enzymatic systems. There are many examples of
encapsulation of biotinylated metal complexes into
protein cavity through specific interactions [32–34].
Biotinylated rhodium complex, [Cp*RhCl2]2, in
streptavidin was utilized for accelerated asymmetric
C–H activation. Rhodium complexes with chiral
(S,S)-Phebox complexes with different alkyl substitu-
ents on the oxazoline rings such as Me, Et, i-Pr, Ph,
and Bn were successfully incorporated in apo-myo-
globin and the composites formed were found to be
good catalysts for hydrosilylation of monosubstituted
and disubstituted alkenes [35]. Literature clearly
revealed that compounds having aromatic ring, hydro-
phobic moiety, donor and acceptor sites are essential
for their binding with myoglobin protein [32–35].
enced to TMS (0.00 ppm), or protio impurity of
DMSO-d6 (2.50 ppm) or CDCl3 (5.70 ppm).
13C NMR spectra were referenced to CDCl3 (77.0
ppm) or DMSO (39.43 ppm). The numbering scheme
used for interpreting NMR spectras is same as that
used for XRD of [Rh(COD)(L{Me})Cl]. Mass spectra
were recorded on a Bruker micrOTOF QII quadru-
pole-time-of-flight mass spectrometer. Elemental
analyses for C, N, and H were performed at the
Campbell Microanalytical Laboratory, University of
Otago. X-ray crystal structures were solved by the Sie-
mens SMART APEX II diffractometer. Intensity data
were collected at 293 K using MoKα radiation.
Synthesis of ligands and Rh complex is shown in
Scheme 2:
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64
ZAFAR et al.
F
C
F
O
S
O
NaH
MeTfO
CH2Cl2
−
O
F
HN
N
O
HN
O
N
O
CH2Cl2
+
N
(HL)
[HL{Me}][OTf]
[L{Me}]
N
(II)
(I)
CH3
CH2Cl2 1/2[Rh(COD)Cl]2
Cl
Rh
N
O
N
Rh([L{Me}])(COD)Cl
(III)
Scheme 2.
Synthesis of N-(pyridin-4-yl)benzamide (HL). was added dropwise over a period of ~2 min causing
4-Aminopyridine (1.52 g, 16.3 mmol) and triethyl- the suspension to become gelatinous. The reaction
amine (3.40 mL, 24.5 mmol, 1.5 eqv.) were combined mixture was heated under reflux for 30 min, then
in dichloromethane (300 mL) under nitrogen, giving a cooled to ambient temperature and filtered. The solid
colourless suspension. Benzoyl chloride (2.30 g, was washed successively with dichloromethane
16.3 mmol) in dichloromethane (75 mL) was added (25 mL) and then with hexane (10 mL) and finally
drop wise with stirring via a pressure equalizing drop- dried in vacuo to give pure I (434 mg, 95%).
ping funnel over a period of 30 min and the solution
stirred for a total of 4 h. After this time, the solvent was For C14H13N2O4F3S · 1/2H2O
evaporated and solid was collected and washed with
Anal. calcd., %
Found, %
C, 45.28
C, 45.56
H, 3.80
H, 3.67
N, 7.54
N, 7.65
cold water (5 mL). Finally the solid product was dried
under high vacuum to give HL (2.66 gm, 83%) which
was used in subsequent reactions without further puri-
fication. All characterisation data of this compound
was obtained as previously reported [39].
IR (ν, cm–1): 3310 w, 3068 w, 1690 m, 1648 m,
1519 m, 1463 m, 1321 m, 1293 m, 1240 s, 1171 m,
1
1028 s, 855 m, 702 m, 515 s. H NMR (DMSO-d6,
300 MHz; δ, ppm (J, Hz)): 11.51 (s., 1H, NH), 8.76
(d., 2H, 3JHH = 6.9, H18, 19), 8.29 (d., 2H, 3JHH = 7.2,
H20, 17), 8.03 (d., 2H, 3JHH = 8.4, H15, 11), 7.74–7.64
Synthesis of [HL{Me}][OTf] (I). HL (250 mg,
1.26 mmol) was placed in a 25 mL three-necked
round-bottomed flask fitted with a condenser and the
flask evacuated. An atmosphere of dry nitrogen was
re-established and the flask was charged with anhy-
(m., 3H, H14, 12), 4.19 (s., 3H, H21). 13C NMR
(DMSO-d6, 75 MHz; δ, ppm): 167.15 (C9), 151.88
drous dichloromethane (15 mL), forming white sus- (C16), 145.80 (C19, 18), 133.09 (C13), 132.86 (C10),
pension. Methyl triflate (428 µL, 3.78 mmol, 3 eqv.) 128.66 (C14, 12), 128.21 (C15, 11), 115 (C20, 17),
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SYNTHESIS, CHARACTERIZATION, AND CATALYTIC ACTIVITY
65
46.31 (C21). Mass spectrometry (ESI): molecular ion using the Amsterdam Density Functional (ADF) 2007
– +
[C13H13N2O]+ [M– CF3SO3 ] mass calcd. 213.1028,
suite of program [40]. Molecular geometry and ener-
gies of I were computed using the generalized gradient
approximation (GGA) with the B3LYP functional [41,
mass found 213.1022.
Synthesis of [L{Me}] (II). To a stirred suspension
of I (200 mg, 552 mmol) in 10 mL of dichloromethane
42]. The molecular orbitals (MOs) were expanded in
at room temperature was added NaH (66 mg,
uncontracted sets of Slater type orbitals (STOs) con-
2.76 mmol, 5 eqv.). The solution was stirred for 5 h
taining diffuse functions with two sets of polarization
and after filtration through celite, the solvent was
functions (TZ2P) [43]. The 1s core shells of carbon,
removed under vacuum to afford a colourless glass.
nitrogen and oxygen and 4p core shell Rh were treated
by the frozen-core approximation. Rh complex geom-
etries were optimized in the gas phase assuming C2v
symmetry. Mulliken population analysis was an
importance property determined to calculate the
degree of charge transfer (CT).
The solid was recrystallised from dichloromethane
and hexane to obtain analytically pure product. The
resulting colorless microcrystalline solid was collected
by filtration, washed with n-hexane (~20 mL) and
dried in vacuo to give pure II (111 mg, 95%).
For C13H12N2O · 5/3H2O
Anal. calcd., %
Found, %
C, 70.00
C, 69.87
H, 5.96
H, 5.69
N, 12.56
N, 12.11
Molecular docking methodology. The RCSB Protein
Data Bank (PDB) [44] was used to download the crys-
tal structure of apo-A71G Myoglobin (PDB, ID:
2EF2). Myoglobin PDB coordinates with lowest
energy and constant conformation were optimized by
molecular dynamic AMBER force field for docking
studies. No water molecules were involved in PDB
molecule. MOPAC 7.0 was used to optimize energy of
the additional hydrogen atoms to obtain a standard
geometry of the structure. The subsequent structure
was exposed to systematic conformational search at
default parameters with RMS gradient of
0.01 kcal mol–1 using Site Finder to find out active
sites of protein. Scoring function was used as basis for
final docking. Different docking runs were used to get
precise binding docking poses. At each step of the sim-
ulation, the energy of interaction of compound with
myoglobin was calculated. The remaining parameters
were set as default.
IR (ν, cm–1): 2956 w, 1646 m, 1586 m, 1551 m,
1488 s, 1425 m, 1347 s, 1306 m, 1260 m, 1260 m,
1190 m, 1166 s, 1018 m, 873 m, 733 m, 674 m, 518 m,
400 m. 1H NMR (CDCl3, 300 MHz; δ, ppm (J, Hz)):
8.24–8.21 (m., 2H, Ph), 7.54–7.52 (m., 2H, H19, 18),
7.43–7.36 (m., 2H, H20, 17 and Ph), 3.74 (s., 3H,
H21). 13C NMR (CDCl3, 75 MHz: δ, ppm): 176.70
(C9), 164.71(C16), 139.91(C20, 17), 139.15 (C10),
130.66 (C13), 129.13 (C19, 18), 127.78 (C14, 12),
118.73 (C15, 11), 44.19 (C21). Mass spectrometry
(ESI): molecular ion [C13H13N2O]+ [M + H]+ mass
calcd. 213.1027; mass found 213.1022.
Synthesis
of
[Rh(COD)(L{Me})Cl]
(III).
[Rh(COD)Cl]2 (40 mg, 0.10 mmol) was added to a
Schlenk tube containing a solution of II (59.26 mg,
0.20 mmol) in toluene (5 mL) and the solution was
stirred for 10 min at room temperature. The product
was filtered as a yellow-white powder (94 mg, 95%).
Crystals of the product were grown in deuterochloro-
form in a NMR-tube.
C–N Coupling methodology. A mixture of the corre-
sponding
4-chloro-1-methylpyridin-1-ium
triflate
(1.1 eqv.), substituted aromatic amine (1 eqv.), anhydrous
potassium carbonate (3 eqv.) and [Rh(COD)(L{Me})Cl]
(1.0 mol %) was refluxed in isopropyl alcohol (5 mL) for
6 h under nitrogen atmosphere. After this time, reaction
mixture was cooled and then filtered to remove potassium
carbonate. Solvent was removed from filtrate under low
pressure. The solid obtained was washed thoroughly with
dichloromethaneand diethyl ether (5 mL each) to remove
unreacted amine. Products were purified by flash chroma-
tography on silica gel using methanol–dichloromethane
(1 : 2) mixture as a mobile phase. and reactions are sum-
1H NMR (CDCl3, 300 MHz: δ, ppm (J, Hz)): 8.2–
8.1 (d.d., 1H, arom.), 7.4–7.3 (m., 2H, arom.), 7.2–
7.1 (m., 4H, arom.), 6.7–6.6 (d.d., 1H, arom.), 5.8–
5.9 (d.d., 1H, arom.), 4.5 (m., 2H, cod CH), 3.51–
3.49 (m., 5H, CH3 & cod CH), 2.35 (m., 4H, cod
CH2), 1.63 (m., 4H, cod CH2). 13C NMR (CDCl3,
75 MHz; δ, ppm): 159.1, 148.9, 137.3, 137.2, 129.2,
124.8, 124.3, 122.2, 116.6, 109.3, 82.8 (cod), 77.4
(cod), 42.7, 31.1 (cod), 30.4 (cod).
Computational study. Geometry optimizations pure
QM computations. All computations were carried out marized along with the yield of the products in Scheme 3:
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66
ZAFAR et al.
NH2
NH2
N
H
N
Rh (I) Catalyst
R
R
+
N
CH3
CF3SO3
CF3SO3
CH3
H
H
N
H
N
N
N
N
N
H3CO
OCH3
44%
O2N
CH3
CH3
CH3
CF3SO3
CF3SO3
O
CF3SO3
80%
21%
H
N
H
N
N
N
NO2
CH3
CH3
O
CF3SO3
CF3SO3
9%
33%
Reaction conditions: substrate ratio of 4-chloro-1-methylpyridin-1-ium triflate to primary amines (1.1 : 1),
K2CO3 (3 eqv.), Rh catalyst (1.0 mol %), isopropyl alcohol (reflux), time (6 h).
Scheme 3.
RESULTS AND DISCUSSION
affording the white deprotonated pyridinium amidate,
[L{Me}] (II), product. To find out the reactivity of II,
it was tested under different conditions as summarized
in Table 1. It was found out that it was protonated,
upon their treatment with triflic acid in DMSO sol-
vent. It did not react with refluxed methanol and water
at room temperature. However, it hydrolyzed fully
upon treatment with refluxed water for 6 h. Signals
assignable to ν(S=O) and ν(C–F) were absent from
the IR spectrum of II, confirming that triflate ion was
not present. The band that was observed at 1690 cm–1
in I was replaced by a new band at 1646 cm–1. The high
resolution mass spectrum (ESI+, [M + H]+) of the
product showed base peak at m/z 213.1022. The NMR
spectrum of II was markedly different to that of I.
Critically, signals attributable to amide NH
group were absent from the 1H NMR and IR spectra.
The N-methyl resonance was observed at 3.83 ppm,
which is shifted upfield from the corresponding signal
for I where it is observed at 4.19 ppm. It was also found
The protonated pyridinium amidate triflate salt,
[HL{Me}][OTf] (I), was synthesized by treatment of
HL with methyl triflate in anhydrous dichlorometh-
ane solution under reflux. The maximum product pre-
cipitated out from the reaction medium in half an
hour. Examination of the IR spectrum of I showed a
band at 3310 cm–1, which is assigned to ν(N–H). The
amide band of this compound was observed at
1690 cm–1. Absorptions assigned to the triflate anion
were observed at 1293, 1240 and 1171 cm–1 ν(S=O)
1
and 1028 cm–1 ν(C–F). The H NMR (DMSO-d6)
spectrum of I has a singlet at 11.51 ppm assigned to the
amide proton. The N-methyl resonance in this com-
pound was observed at 4.19 ppm.
To determine whether the cationic N-methyl pyri-
dinium compound I could be converted into the cor-
responding neutral compound, [HL{Me}][OTf] was
stirred with sodium hydride in dichloromethane sol-
vent at room temperature. After 5 h, the solution was that the 1H NMR spectrum for II displays two multi-
filtered and the solvent was removed under vacuum plets rather than doublets for four proton (H9-12) in
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SYNTHESIS, CHARACTERIZATION, AND CATALYTIC ACTIVITY
Table 1. Reactivity of [L{Me}]
67
Reaction conditions
Observations and results
Solid was treated to Triflic acid (1 : 2) in DMSO
Protonated
20 mg of solid was dissolved in methanol and the solution was No reaction
refluxed for 30 mins. After that the solvent was removed under
reduced pressure using a rotary evaporator at 40°C
20 mg of solid was dissolved in 0.75 mL of DMSO containing No hydrolysis
few drops of water and was left for 48 h
20 mg of solid was dissolved in a 1 mL solution containing 10% No hydrolysis of ligand occur even after two hours
H2O/THF and was refluxed. After that the solvent was
removed under vacuum on a rotary evaporator at 40°C (5 min)
20 mg of solid was suspended 1 mL H2O and was refluxed for Fully hydrolyzed and resulted in benzoate anion and cor-
responding cation
about 6 h. After that the solvent was removed under vacuum on
a rotary evaporator at 40°C
the pyridinium ring, owing to the considerable dou- C–N (1.39 Å) [3] in amide ligand. Similarly C(17)–
ble-bond character and restricted rotation of the C(18), C(19)–C(20), shortened compared to C(16)–
C(16)–N(1) bond. Johnson also found this restricted C(20) and C(16)–C(17) (by 0.04 and 0.05 Å respec-
rotation of the exocyclic C–N bond for pyridinium tively), suggesting that N-(1-methylpyridin-4(1H)-
amide ligand that resulted in four proton environ- ylidene)benzamide resonance structure is more predom-
ments (H17-20) for the nitrogen containing ring [45]. inant.
Energies of frontier molecular orbitals, i.e.,
[Rh(COD)(L{Me})Cl][OTf] was synthesized via
HOMO and LUMO energies, are significantly
the similar path used by Hermann for carbenes [46].
important characteristic parameters for electronic
[Rh(COD)Cl]2 was used as rhodium source owing to
structure methods. LUMO represents electron
its solubility in toluene that was allowed to react with
accepting characteristics of a molecule, whereas
[L{Me}] in a Schlenk tube. The yellow product,
HOMO denotes the capability of a molecule to donate
formed in excellent yield within 10 min, filtered as a
an electron [48]. A critical parameter in determining
1
yellow-white powder. The H NMR of the complex
molecular stability and electrical transport properties
showed aromatic signals in the extended range of 8.2–
is energy gap (∆E) between HOMO and LUMO. ∆E
6.0 ppm as compared to [L{Me}], 8.2–7.4 ppm. Simi-
is also a measure of electron conductivity of a com-
larly trend of aromatic signals is shown in the 13C
pound as well [49]. Figure 2 reveals the patterns of the
NMR of the complex (159.1–109.3 ppm) as compared
to [L{Me}] (176.7–118.7 ppm). In addition, Rhodium
coordinated cyclooctadiene showed four signals, more
shielded methylene appeared upfield and less shielded
methine appeared downfield like in case of
[Rh(COD)(NHC)Cl] [47]. Signals due to methyl are
also shifted as compare to protonated and deproton-
ated ligands. Crystals of the product were grown in
deuterochloroform in an nmr tube. An ORTEP depic-
tion is shown in Fig. 1.
HOMO and LUMO of III calculated with the B3LYP
functional. The positive phase is symbolized with blue
and the negative phase orange. HOMO and LUMO
energies of the III are also listed along with their
molecular orbitals. It can be seen that the HOMO
and LUMO of Rh(L{Me})(COD)Cl are –5.7255 and
–5.0363 eV, respectively, which shows (∆E) was found
to be –0.6892 eV. Figure 3 depicts that it is easier for
the vertical transitions from the 1s of Rh and 2p of N to
jump from HOMO to LUMO due to smaller band gap.
To further apprehend the electronic transitions of
Rh(L{Me})(COD)Cl, TDDFT/B3LYP DZ was
applied to investigate the nature and the energy of
absorption spectra on the basis of the optimized geom-
etry. The electronic absorption spectrum was simu-
lated by the Double zeta basis functions with the sin-
glet energies from calculations. Figure 4 depicts the
electronic transition for the singlet excited state com-
pound exhibiting λmax at 630 nm other important tran-
sitions to be at 520 and 280 nm.
DFT studies were performed on the Rh(L{Me})-
(COD)Cl (III) to gain a greater insight into the structural
and electronic changes that occur upon deprotonation
and complexation of I with rhodium precursor. Calcu-
lated and experimental bond lengths as well as angles of
III are compared in Tables 2 and 3. The results showed
best agreement with experimental determined values
given that some differences are expected between the
solid-state and gas-phase structures. Analogous to the
DFT calculations, X-ray structures confirmed signifi-
cant structural changes occur upon deprotonation and
In the field of quantum chemistry, calculation of
complexation of [HL{Me}][Cl] to form III. There is a effective atomic charges play a significant role in the
shortening of C(16)–N(1) (1.37 Å) compared to normal application of molecular systems. The MPA shows
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ZAFAR et al.
C(13)
C(12)
C(14)
C(15)
C(3)
C(2)
C(11)
O(1)
C(4)
C(10)
C(1)
C(9)
C(5)
Cl
Rh
C(7)
C(6)
N(1)
C(8)
C(16)
Cl(2)
C(20)
C(19)
C(17)
C(18)
Cl(1)
C(25)
Cl(3)
N(2)
C(21)
Fig. 1. ORTEP diagram of Rh(L{Me})(COD)Cl (III).
(Fig. 5, Table 4), that presence of two N-atoms, i.e.,
The MEP map is a convenient way to investigate
N(1) = –0.572, N(2) = –0.486 and one O-atom, the electrophilic and nucleophilic regions [50]. MEP
O(1) = 0.570, imposes distribution large positive demonstrates molecular size, shape, positive, negative
charges on C(9) = 0.544. Alternatively all C-atoms of and neutral regions based on color grading. In Fig. 6,
aromatic ring possess negative charges due to delocal- MEP displays the most negative region associated
ization of π-electrons. Importantly highly electropos- with the lone pair of N(1) followed by O(1) atom.
itive atom with Mullikan charge distribution is Rh = MEP increases in the order of red, orange, yellow,
0.517 due to N(1). All hydrogen atoms have positive green, blue. The areas having excess of electrons are
charge distribution.
represented by negative potential with red and yellow
Table 2. Selected bond lengths (Å) for [Rh(L{Me})(COD)Cl] determined by X-ray diffraction method and DFT calcula-
tions
Bond lengths
XRD
DFT
Bond lengths
XRD
DFT
Bond lengths
XRD
DFT
Rh–Cl
2.39
2.14
2.12
2.12
2.14
2.10
2.38
2.14
2.14
2.14
2.13
2.14
C(9)–N(1)
C(9)–O(1)
C(10)–C(11)
C(16)–N(1)
C(16)–C(17)
C(16)–C(20)
1.38
1.23
1.39
1.37
l.41
1.40
1.22
1.40
1.39
1.41
1.41
C(17)–C(18)
C(18)–N(2)
C(19)–N(2)
C(19)–C(20)
C(21)–N(2)
C(1)–C(8)
1.36
1.34
1.35
1.36
1.48
1.41
1.37
1.34
1.34
1.39
1.41
1.40
Rh–N(1)
Rh–C(1)
Rh–C(4)
Rh–C(5)
Rh–C(8)
1.41
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Table 3. Selected bond angles (deg) for title compound [Rh(L{Me})(COD)Cl] determined by X-ray diffraction and DFT
calculations
Bond angles
XRD
DFT
Bond Angles
XRD
DFT
ClRhN(1)
C(4)RhC(8)
C(4)RhCl
C(9)N(1)C(16)
C(21)N(2)C(19)
C(9)C(10)C(15)
N(1)RhC(1)
C(9)C(10)C(11)
C(11)C(12)C(13)
O(1)C(9)C(10)
89.24
98.7
91.9
118.5
120.2
122.3
93.2
119.1
119.7
119.1
89.20
97.7
96.5
118.0
120.0
122.1
92.0
120.7
120.4
119.0
C(12)C(13)C(14)
N(1)C (9)O(1)
120.1
124.8
119.5
121.8
120.7
119.5
120.2
119.6
115.6
121.6
118.0
124.0
120.0
120.5
119.9
120.5
119.9
120.9
115.0
120.5
C(11)C(10)C(15)
C(20)C(19)N(2)
C(16)C(17)C(18)
C(18)N(2)C(19)
C(18)N(2)C(21)
C(19)C(20)H(20)
C(17)C(16)C(20)
C(17)C(18)N(2)
color (C=C group, oxygen and nitrogen atoms), square deviations were selected for docking pose of the
whereas electron deficient regions are expressed by the
regions having the positive potential with hydrogen
atoms.
compound. Rh complex interacts with amino acid res-
idues like His 93, Phe 138, Leu 104, Ile 107, Ile 99,
Leu 72, Leu 29, Phe 43, His 64, Val 68, Thr 67 and
Leu 89 of 2EF2 pocket via van der Wall’s interactions
as illustrated in Fig. 7. Binding strength (Kb) of Rh
complex with 2EF2 was calculated from Gibbs free
energy (∆G) of complexation, which showed signifi-
cant binding affinity between two. Moreover, negative
From molecular docking analysis of myoglobin
protein targets with III using docking procedure, it
can be deduced that intermolecular hydrophobic and
stacking interactions are involved in stabilizing the
computationally predicted lowest energy adduct.
Minimum binding free energy and lowest root mean value of ∆G indicates that interaction process of Rh
LUMO = –5.0363 eV
ΔE = –0.6892 eV
LUMO = –5.7255 eV
Fig. 2. Surfaces of the frontier molecular orbitals Rh(L{Me})(COD)Cl using the generalized gradient approximation (GGA) with
the B3LYP functional.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 45 No. 1 2019

70
ZAFAR et al.
–0.06
–0.08
–0.10
–0.12
–0.14
–0.16
–0.18
–0.20
–0.22
–0.24
–0.26
–0.28
–0.30
–0.32
C
Rh
Cl
N
O
Rh
Fig. 3. Energy level digram of III using the generalized gradient approximation (GGA) with the B3LYP.
complex with 2EF2 is spontaneous [51]. Binding con- also observed that ortho analogues of amines are
less active than para, owing to more steric bulk
close to aniline nitrogen that can hinder its reactivity
with4-chloro-1-methylpyridin-1-iumtriflate.2-Ami-
noanthracene-9,10-dione yield 33% of product due to
electron with drawing carbonyl groups on anthracene
ring.
stant, free energy and other calculated parameters
(octanol/water partition coefficient (P), molar refrac-
tivity (MR) and van der Wall’s (VDW) surface area are
given below:
Binding
constant
Free
energy∆G,
Slog P
5.096
MR
9.94
VDW
Kb, M–1
kJ mol–1
–17.48
In sammary, neutral monodentate nitrogen donor
N-(1-methylpyridin-4(1H)-ylidene)benzamide (PYA)
ligand was synthesized by abstraction of proton from
its protonated triflate salt, [HL{Me}][OTf], with
sodium hydride. [Rh(COD)(L{Me})Cl] was synthe-
sized by addition of PYA ligand to [Rh(COD)Cl]2 in
dichloromethane solvent. Single crystal of
[Rh(COD)(L{Me})Cl] was successfully grown and its
structure was determined. Geometric parameters
obtained by this method were found comparable with
DFT results. HOMO and LUMO energy analysis,
MEP, Mulliken atomic charges and electronic proper-
ties of the Rh complex have been calculated by using
generalized gradient approximation (GGA) with
1.158 × 103
383.54
To gauge the potential utility of the PYA ligand as
supporting ligands, preliminary C–N cross-coupling
experiments with [Rh(COD)(L{Me})Cl][OTf] were
carried out. The results obtained for coupling of vari-
ous substituted amines with 4-chloro-1-methylpyri-
din-1-ium triflate are mentioned in Scheme 3. Maxi-
mum yield was obtained for 4-methoxyaniline and
least for 2-nitroaniline. The lone pair on 4-methoxy-
substituted on aniline enhances the nucleophilic char-
acter of amine by resonance effect. The electron with
drawing substituted nitro deactivates the aniline. It is B3LYP functional method. HOMO and LUMO
Density of states
4
3
2
1
400
500
600
700
Eigenvalue, nm
Fig. 4. Energy level plot of III using the generalized gradient approximation (GGA) with the TDDFT/B3LYP DZ.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 45 No. 1
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SYNTHESIS, CHARACTERIZATION, AND CATALYTIC ACTIVITY
71
H/0.393
H/0.393
H
C/0.019
C/–0.288
C/–0.128
H/0.311
H/0.150
C–/–0.069
C/0.138
H/0.394
288
C/0.082
H/0.323
C/–0.290
O/–0.570
C/0.544
Rh++/–0.517
Cl/–0.517
C/–0.286
C/–0.103
N/–0.572
C/–0.295
H/0.321
C/0.060
C/–0.321
H/0.150
H/0.363
C/–0.253
C/–0.294
C/–0.139
H/0.150
C/0.315
H/0.150
C/–0.129
N+/–0.486
H/0.351
H/0.363
H/0.363
C/0.246
H/0.363
H/0.363
Fig. 5. Optimized molecular geometry and Mullikan population charges of III using the generalized gradient approximation
(GGA) with the B3LYP functional.
Muliken charge
0.5170
0.2450
–0.0277
–0.3000
–0.5720
Fig. 6. Molecular electrostatic potential (PES) of Rh(L{Me})(COD).
energy gap indicated the eventual charge transfer protein, a potential biomarker of acute myocardial
interactions taking place within the molecule. Strong infection, suggests its potential as myoglobin sensor
interaction of [Rh(COD)(L{Me})Cl] with myoglobin and as an artificial enzyme. [Rh(COD)(L{Me})Cl]
Table 4. Mullikan population analysis of [Rh(L{Me})(COD)Cl] using the generalized gradient approximation (GGA) with
the B3LYP functional
Atoms
Charge analysis
Atoms
Charge analysis
Atoms
Charge analysis
Rh
0.517
–0.572
–0.486
–0.570
Cl
–0.015
0.544
–0.290
–0.295
C(12)
C(16)
H(19)
H(20)
–0.294
0.060
0.150
N(1)
N(2)
O(1)
C(9)
C(14)
C(13)
0.150
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72
ZAFAR et al.
(a)
(b)
Ile
107
Ile
99
Leu
104
Phe
138
Leu
72
Cl
C–
Rh
His
93
O
C–
Leu
29
N+
N+
Val
68
Phe
43
Leu
89
His
64
Thr
67
Fig. 7. Visuals of docking interactions of Rh complex with 2EF2 enzyme (a), 2D ligplots showing interactions of amino acid res-
idues of 2EF2 with Rh complex (b).
15. Navarro, M., Li, M., Muller-Bunz, H., et al., Chem.
Eur. J., 2016, vol. 22, p. 6740.
16. Burgess, M.G., Zafar, M.N., Horner, S.T., et al., Inorg.
Chim. Acta, 2016, vol. 450, p. 124.
also proved to be a good catalyst for C–N coupling
reactions. Electron donor para-substituted amines
were found to be most active to couple with 4-chloro-
1-methylpyridin-1-ium triflate.
17. Dragnea, B., Chen, C., Kwak, E.-S., et al., J. Am.
Chem. Soc., 2003, vol. 125, p. 6374.
REFERENCES
18. Braha, O., Walker, B., Cheley, S., et al., Chem. Biol.,
1. Hopkinson, M.N., Richter, C., Schedler, M., and Glo-
1997, vol. 4, p. 497.
rius, F., Nature, 2014, vol. 510, p. 485.
19. Xiao, Y., Patolsky, F., Katz, E., Hainfeld, J.F., and
2. Peris, E., Chem. Rev., 2017. doi 10.1021/acs.chem-
Willner, I., Science, 2003, vol. 299, p. 1877.
rev.6b00695
20. Benson, D.E., Wisz, M.S., and Hellinga, H.W., Curr.
Opin. Biochem., 1998, vol. 9, p. 370.
3. Boyd, P.D.W., Wright, L.J., and Zafar, M.N., Inorg.
Chem., 2011, vol. 5, p. 10522.
21. Lu, Y., Berry, S.M., and Pfister, T.D., Chem. Rev.,
4. Redmore, S.M., Rickard, C.E.F., Webb, S.J., and
2001, vol. 101, p. 3047.
Wright, L.J., Inorg. Chem., 1997, vol. 36, p. 4743.
22. Straface, A.L., Myers, J.H., Kirchick, H.J., and
5. Zhang, J., Liu, Q., Duan, C., et al., Dalton Trans.,
Blick, K.E., Am. J. Clin. Pathol., 2008, vol. 129, p. 788.
2002, vol. 14, p. 591.
23. McCord, J., Nowak, R.M., McCullough, P.A., et al.,
6. Rowland, J.M., Thornton, M.L., Olmstead, M.M.,
and Mascharak, P.K., Inorg. Chem., 2001, vol. 40,
p. 1069.
Circulation, 2001, vol. 104, p. 1483.
24. Sallach, S.M., Nowak, R., Hudson, M.P., et al., Am. J.
Cardiol., 2004, vol. 94, p. 864.
25. Apple, F.S., Christenson, R.H., Valdes, R., et al., Clin
Chem., 1999, vol. 45, p. 199.
26. Zhang, B., Tamez-Vela, J.M., Solis, S., et al., Med.
Eng., 2013, vol. 2013, p. 1.
7. Qi, J.Y., Ma, H.X., Li, X.J., et al., Chem. Commun.,
2003, vol. 11, p. 1294.
8. Qi, J.Y., Qiu, L.Q., Lam, K.H., et al., Chem. Commun.,
2003, vol. 9, p. 1058.
~
9. Muniz, K. and Iglesias, A., Angew.Chem. Int. Ed.,
27. Debreczeni, J.E., Bullock, A.N., Atilla, G.E., et al.,
2007, vol. 46, p. 6350.
Angew. Chem. Int. Ed., 2006, vol. 45, p. 1580.
10. Fortney, C.F. and Shepherd, R.E., Inorg. Chem. Com-
28. Lu, Y., Angew. Chem. Int. Ed., 2006, vol. 45, p. 5588.
mun., 2004, vol. 7, p. 1065.
29. Ohashi, M., Koshiyama, T., Ueno, T., et al., Angew.
Chem. Int. Ed., 2003, vol. 42, p. 1005.
11. Wong, C.M., Peterson, M.B., Pernik, I., et al., Inorg.
Chem., 2017, vol. 56, p. 14682.
30. Ueno, T., Ohashi, M., Kono, M., et al., Inorg. Chem.,
12. Busetto, L., Cassani, M.C., Femoni, C., et al., Organo-
2004, vol. 43, p. 2852.
metallics, 2011, vol. 30, p. 5258.
31. Ueno, T., Koshiyama, T., Ohashi, M., et al., J. Am.
Chem. Soc., 2005, vol. 127, p. 6556.
13. Vuong, K.Q., Timerbulatova, M.G., Peterson, M.B.,
et al., Dalton Trans., 2013, vol. 42, p. 14298.
14. Donnelly, K.F., Segarra, C., Shao, L.X., et al., Organo- 32. Li, C. and Xiao, J., J. Am. Chem. Soc., 2008, vol. 130,
metallics, 2015, vol. 34, p. 4076. p. 13208.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY
Vol. 45
No. 1
2019

SYNTHESIS, CHARACTERIZATION, AND CATALYTIC ACTIVITY
73
33. Dürrenberger, M., Heinisch, T., Wilson, Y.M., et al., 42. Becke, A.D., Phys. Rev., A., 1998, vol. 38, p. 3098.
Angew. Chem. Int. Ed., 2011, vol. 50, p. 3026.
43. Lee, C., Yang, W., and Parr, R.G., Phys. Rev., B: Con-
34. Creus, M., Pordea, A., Rossel, T., et al., Angew. Chem.
dens. Matter Mater. Phys., 1988, vol. 37, p. 785.
Int. Ed., 2008, vol. 47, p. 1400.
44. Protein Data Bank. https://www.rcsb.org/pdb/home/
home.do. Accessed December 27, 2017.
35. Xu, L., Zhu, Q., Huang, G., et al., J. Org. Chem., 2012,
vol. 77, p. 3017.
45. Doster, M.E. and Johnson, S.A., Angew. Chem. Int.
36. Beyramabadi, A. and Morsali, A., Int. J. Phys. Sci.,
Ed., 2009, vol. 121, p. 2219.
2011, vol. 6, p. 1780.
46. Herrmann, W.A., Schütz, J., Frey, G.D., and
37. Monajjemi, M., Sayadian, M., Zare, K., et al., Int. J.
Herdtweck, E., Organometallics, 2006, vol. 25, p. 2437.
Phys. Sci., 2011, vol. 6, p. 4063.
47. Wolf, S. and Plenio, H., J. Orgmet. Chem., 2009, vol.
38. Zafar, M.N., Masood, S., Nazar, M.F., et al., J. Chin.
Chem. Soc., 2017, vol. 64, p. 1.
694, p. 1487.
48. Honorio, K.M. and Da Silva, A.B.F., Int. J. Quant.
39. Epsztajn, J. and Jozwiak, A., Eur. J. Org. Chem., 2004,
Chem., 2003, vol. 95, p. 126.
vol. 2004, p. 3254.
49. Li, Y., Yang, M.M., Liu, Y.Y., et al., J. Mol. Struct.,
40. Velde, G.T., Bickelhaupt, F.M., Gisbergen, S.J.A.,
2011, vol. 987, p. 206.
et al., J. Comput. Chem., 2001, vol. 22, p. 931.
50. Li, Y., Zhang, H., Liu, Y.Y., et al., J. Mol. Struct., 2011,
41. Baerends, E.J., Amsterdam Density Functional (ADF
vol. 997, p. 110.
2013), Software for Chemistry and Materials (SCM),
Theoretical Chemistry, Amsterdam: Vrije Univ. http:// 51. Kryger, G., Silman, I., and Sussman, J., J. Physiol.,
www.scm.com.
1998, vol. 92, p. 191.
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