Copper (II) complexes of 3,5-di-tert-butyl-2-hydroxybenzoylhydrazones of 2-formylpyridine and 2-acetylpyridine, with tautomeric azine-scaffold-based architecture: Synthesis, crystal structures, the effect of counteranions on complexation, and their anti-m

Article abstract of DOI:10.1002/aoc.4840

A series of air- and moisture-stable copper (II) complexes of 3,5-di-tert-butyl-2-hydroxy-N′-(pyridin-2-ylmethylene)benzohydrazide (L1H) and 3,5-di-tert-butyl-2-hydroxy-N′-(1-(pyridin-2-yl)ethylidene)benzohydrazide (L2H) were synthesized. The two newly de

Full text of DOI:10.1002/aoc.4840

Received: 18 September 2018
DOI: 10.1002/aoc.4840
Revised: 14 December 2018
Accepted: 8 January 2019
F U L L P A P E R
Copper (II) complexes of 3,5‐di‐tert‐butyl‐2‐
hydroxybenzoylhydrazones of 2‐formylpyridine and 2‐
acetylpyridine, with tautomeric azine‐scaffold‐based
architecture: Synthesis, crystal structures, the effect of
counteranions on complexation, and their anti‐microbial
and anti‐tuberculosis evaluation
Ganesh S. Hegde1,2
| Sandeep P. Netalkar1
| Vidyanand K. Revankar1
1 Department of Chemistry, Karnatak
University, Pavate Nagar, Dharwad 580
003, Karnataka, India
2 Department of Chemistry, M. E. S., M.
M. Arts & Science College, Sirsi, Uttara
Kannada 581 402, Karnataka, India
A series of air‐ and moisture‐stable copper (II) complexes of 3,5‐di‐tert‐butyl‐2‐
hydroxy‐N′‐(pyridin‐2‐ylmethylene)benzohydrazide (L1H) and 3,5‐di‐tert‐
butyl‐2‐hydroxy‐N′‐(1‐(pyridin‐2‐yl)ethylidene)benzohydrazide (L2H) were
synthesized. The two newly designed hydrazone Schiff base ligands with the
tautomeric azine‐scaffold involving N, N and O ligating architecture were
derived from the condensation of 3,5‐di‐tert‐butyl‐2‐hydroxybenzoylhydrazide
with 2‐formylpyridine and 2‐acetylpyridine, respectively. The resultant ligands
and their copper complexes were characterized using various spectro‐analytical
techniques, like infrared (IR), 1H‐NMR, 13C‐NMR, electron paramagnetic reso-
nance, electronic spectroscopy, thermogravimetric analysis and conductance
measurements. The interesting inter‐convertible E/Z geometrical isomeric
forms of the ligand L1H was established by NMR and IR spectra. In addition,
the molecular structures of L2H, C3 and C4 were unambiguously established
using the single‐crystal X‐ray diffraction technique. The dichlorido‐bridged
dinuclear square pyramidal complexes, with the [Cu2(μ‐Cl)2L2] type of core
units, were resulted for the complexes C1 and C3, whereas z‐in compressed
mononuclear 1:2 (M:L) octahedral complex geometries resulted for C2, C4
and the rest of the complexes even when various copper (II) precursor salts
with different counteranions were used. The ligands and their complexes were
investigated for the anti‐microbial activities against gram‐positive and gram‐
negative bacteria. The ligand L2H and its complexes C3 and C4 exhibited bet-
ter anti‐tuberculosis activity than the controls.
Correspondence
V. K. Revankar, Department of Chemistry,
Karnatak University, Pavate Nagar,
Dharwad‐580 003, Karnataka, India.
Email: vkrevankar@rediffmail.com
Funding information
Minor Research Project Program MRP(S)‐
0475/13‐14/KAKA089/UGC‐SWRO
KEYWORDS
anti‐microbial, anti‐tuberculosis, azine‐scaffold, copper complexes, single‐crystal X‐ray diffraction
technique
Appl Organometal Chem. 2019;e4840.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4840

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HEGDE ET AL.
1 | INTRODUCTION
2 | EXPERIMENTAL
The chemistry of hydrazones and their coordination
compounds continues to receive much attention because
hydrazides and their hydrazones can function as bioac-
tive compounds.[1] Among these, the aroyl hydrazones
are the important and interesting series of hydrazone‐
derived ligands in the coordination chemistry, because
of their ability to coordinate to the metal through the
imine nitrogen as well as through the amide oxygen in
either protonated or deprotonated form. An additional
donor site can, however, be incorporated in the aroyl
hydrazone ligands by carefully choosing such aldehydes
or ketones that have donor atoms like nitrogen or oxy-
gen at appropriate positions that can react with a hydra-
zide, forming the tridentate aroyl hydrazone Schiff bases.
This flexibility of modifying the ligand design with
appropriate additional donor atoms as well as the ease
of its synthesis makes these ligands of considerable
interest from the perspective of coordination geometry.
Among the coordination complexes of hydrazones, cop-
per (II) hydrazone complexes have received special
attention primarily because of their structural diversity,
redox and magnetic properties,[2] which makes them
potential candidates for use in catalysis as well as in
biological applications.[3–6] Copper being an important
biologically significant metal, its hydrazone complexes
show interesting biological properties, like, bacteriostatic
activity,[7] effective DNA binding,[8] anti‐microbial[9] and
anti‐tuberculosis activities,[10] etc. With tridentate
ligands, Cu (II) can form both mononuclear and
binuclear complexes depending on the stoichiometric
reaction between the ligand and the metal ion. Com-
monly observed geometry is square pyramidal or
distorted octahedral. The Cu (II) ion prefers distorted
octahedral geometry when the stoichiometric reaction
is 1:2 and square pyramidal with 1:1 stoichiometric
reaction with respect to metal and ligand. However,
the presence of the bridging group in the ligand may
lead to binuclear complexes usually in square pyramidal
complexes.
2.1 | Materials and physical
measurements
All the reagents used in this study were purchased from
Sigma‐Aldrich and used without further purification.
1
The H‐ and 13C‐NMR spectra were recorded on AV400‐
Bruker 400 MHz High‐Resolution Multinuclear FT‐NMR
Spectrometer and Agilent 400MR DD2 spectrometers, in
CDCl3 (1H‐NMR: 400 MHz; 13C‐NMR: 100 MHz) at room
temperature using TMS as an internal reference. Fourier
transform‐infrared (FT‐IR) spectra were recorded in a
KBr disc matrix using an Impact‐410 Nicolet (USA) FT‐
IR spectrometer over the range of 4000–400 cm−1. The
mass spectra of the ligands were obtained on SHIMADZU
GCMS‐QP2010S. Electron paramagnetic resonance (EPR)
spectra of copper (II) complexes were recorded on Varian
E–4 X‐band EPR spectrometer, using TCNE as the
<g> marker. The electronic spectra were measured on a
Hitachi 150–20 spectrophotometer over the range of
800–200 nm. Thermal analyses of the metal complexes
were carried out on a Universal V2.4F TA instrument,
keeping the final temperature at 1000°C and the heating
rate at 10°C per min. The X‐ray diffraction data were
obtained at 296 K on Bruker X8 Proteum diffractometer.
Intensity measurements were performed using mono-
chromatic Cu‐Kα‐radiation with λ = 1.54178 Å. Using
Olex2,[11] the structure was solved with the SIR2004[12]
structure solution program using Direct Methods and
refined with the XH refinement package using CGLS
minimization. Molecular graphics were generated using
ORTEP‐3, Mercury and Cameron.[13–15]
2.2 | Synthesis of ligands (L1H and L2H)
3,5‐di‐tert‐butyl‐2‐hydroxy‐N′‐(1‐(pyridin‐2‐yl)
methylidene)benzohydrazide (L1H) and 3,5‐di‐tert‐
butyl‐2‐hydroxy‐N′‐(1‐(pyridin‐2‐yl)ethylidene)
benzohydrazide (L2H)
Inspired by the naturally occurring biologically signif-
icant metalloenzymes containing copper active sites, the
present investigation was undertaken to study the nature
of coordination modes of the aroyl hydrazone ligands
with copper (II) salts. The two novel ligands 3,5‐di‐tert‐
butyl‐2‐hydroxy‐N′‐(1‐(pyridin‐2‐yl)methylidene)benzohy
drazide (L1H) and 3,5‐di‐tert‐butyl‐2‐hydroxy‐N′‐(1‐
(pyridin‐2‐yl)ethylidene)benzohydrazide (L2H) were pre-
pared, and their structural diversity with copper (II) ions
while varying the counteranions is the focus of the
current study. The complexes were also evaluated for
anti‐microbial and anti‐tuberculosis activities.
The ligands L1H and L2H were prepared in three
steps. First, the starting material, methyl 3,5‐di‐tert‐
butyl‐2‐hydroxybenzoate 1 was synthesized following
the literature method.[16] The ligand precursor
3,5‐di‐tert‐butyl‐2‐hydroxybenzoylhydrazide 2 was syn-
thesized by treating 1 with hydrazine hydrate following
the common procedure as in Vogel,[17] in the second step.
The benzoyl hydrazone ligands were prepared in the
third step as follows.
3,5‐Di‐tert‐butyl‐2‐hydroxybenzoylhydrazide (2), 0.005
moles, in methanol (100 ml) was treated with 0.005 moles
of pyridine‐2‐aldehyde for L1H and 2‐acetylpyridine for

HEGDE ET AL.
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L2H taken in the round‐bottom flasks separately. The
reaction mixtures were stirred at room temperature for
nearly an hour until the off‐white precipitates resulted.
The reaction products were then filtered off, dried and
recrystallized from methanol resulting in the formation
of ligands L1H and L2H with 80% yields in each case.[18]
Schematic representation of the syntheses of the ligands
and numbering pattern for NMR assignment is given in
Scheme 1.
pyridine C=N (1591), imine >C=N‐ (1631), OH (3426s),
NH (3288), C‐O (1278). H‐NMR (CDCl3, 400 MHz): δ
1
15.94 (s, 1H, hydrazine NH), 12.80 (s, 1H, C(2)‐phenolic
OH), 7.52(d, J = 1.6 Hz, 1H, C4H, aromatic), 7.55 (d, J
= 2 Hz 1H, C6H, aromatic), 7.68 (d, J = 8 Hz, 1H,
C11H, aromatic), 7.96 (t, J = 8 Hz, 1H, C12H aromatic),
7.44 (t, J = 6.2 Hz, 1H, C13H aromatic), 8.76 (d, J = 4.8
Hz, 1H, C14H, aromatic). 13C‐NMR (DMSO, ppm):
153.3 (HC8 = N), 29.3, 31.5, 34.3, 35.2 (t Bu), 168.7
(‐N=C7 = O), 159.8 (C2‐OH phenolic), 112.7 (C1, aro-
matic), 138.1 and 138.0 (C3 and C5, aromatic), 124.3
and 124.4 (C4 and C6, aromatic), 147.2 (C10, aromatic),
119.8 (C11, aromatic), 139.7 (C12, aromatic), 129.0 (C13,
aromatic), 143.7 (C14, aromatic). UV–Vis (CHCl3): λmax
L1H: yield: 80%; m.p.: 180°C; anal. calcd for
C21H27N3O2 (%): C, 71.27; H, 7.65; N, 11.91. Found (%):
C, 71.29; H, 7.69; N, 11.88. FT‐IR (cm−1): C=O (1683),
pyridine C=N (1588), imine >C=N‐ (1630), OH (3427s),
1
NH (3287), C‐O (1253). H‐NMR (CDCl3, 400 MHz): δ
15.63 (s, 1H, hydrazine NH), 12.64 (s, 1H, C(2)‐phenolic
OH), 8.73 (s, 1H, ‐HC=N), 7.45 (s, 1H, C4H, aromatic),
7.49 (s, 1H, C6H, aromatic), 8.04 (d, J = 8 Hz, 1H,
C11H, aromatic), 7.67 (t, J = 7.6 Hz, 1H, C12H aromatic),
7.18 (t, J = 6 Hz, 1H, C13H aromatic), 8.46 (d, J = 15.6
Hz, 1H, C14H, aromatic), 2.48 (s, 3H, CH3OH solvent).
13C‐NMR (CDCl3, 100 MHz, ppm): 148.9 (HC8 = N),
29.3, 31.3, 34.3, 35.2 (t Bu), 159.3 (‐N=C7 = O), 152.6
(C2‐OH phenolic), 112.0 (C1, aromatic), 138.1 and 138.0
(C3 and C5, aromatic), 124.5 and 124.3 (C4 and C6, aro-
matic), 140.2 (C10, aromatic), 121.5 (C11, aromatic),
136.9 (C12, aromatic), 129.7 (C13, aromatic), 138.8 (C14,
aromatic), 169.2 (CH3OH, solvent). UV–Vis (CHCl3): λmax
(nm), (ε
(Lmol−1cm−1)): 268 (4,558.0), 342 (6,531.4),
max
m/z: 367.48.
2.3 | Synthesis of copper (II) complexes
The ligands L1H/L2H (2 mmol) and methanol (30 ml)
were charged into a 100‐ml round‐bottom flask and
allowed to warm with stirring in an oil bath maintained
at 60–65°C. Hot methanolic solutions of copper (II) salts
(1 mmol) were added to this dropwise with stirring. After
the complete addition of metal salt solution, the reaction
mixture was further refluxed for about 30–40 min at the
same temperature. The isolated complexes were filtered
in hot conditions, washed with hot ethanol and dried.[19]
The schematic route for the synthesis of Cu (II) com-
plexes is presented in Scheme 2.
(nm), (ε
(Lmol−1cm−1)): 304 (4,765.3), 340 (2,942.8).
max
m/z: 353.49.
L2H: yield: 80%; m.p.: 185°C; anal. calcd for
C22H29N3O2 (%): C, 71.86; H, 7.98; N, 11.45. Found (%):
C, 71.84; H, 7.95; N, 11.43. FT‐IR (cm−1): C=O (1683),
SCHEME 1 Synthetic route for the
preparation of Schiff base ligands L1H
and L2H
SCHEME 2 Synthetic route for the synthesis of the Cu (II) complexes, C1, C2, C3 and C4

4 of 15
HEGDE ET AL.
C1: yield: 65%; anal. calcd for Cu2C42H52N6O4Cl2 (%):
effect on the complexation with the ligands. However,
for both L1H and L2H, except chlorides, other anions
did not enter the coordination sphere and all of them
resulted in the same complex. Hence, only two distinct
types of complexes for each ligand were considered for
the elaborate study. The ligands L1H and L2H and their
corresponding copper (II) complexes were soluble in
common organic solvents like chloroform, dichlorometh-
ane, methanol, ethanol, acetonitrile, DMF and DMSO,
etc. The yields of all the complexes were substantial. Slow
evaporation of the ligand L2H in methanol and the com-
plexes [Cu2Cl2(L2)2] (C3) in methanol and [Cu(L2)2] (C4)
in chloroform resulted in the single crystals suitable for
X‐ray diffraction (XRD) studies. The stoichiometries of
the metal ions and ligands were established by the metal
estimations, CHN analysis and molar conductivity mea-
surements. All the metal complexes melt above 300°C.
The metal to ligand ratios for [Cu2Cl2(L1)2] (C1) and
[Cu2Cl2(L2)2] (C3), i.e. Cu (II) complexes with copper
chloride as metal precursors exhibited 2:2 molar ratios
for metal:ligand, while the Cu (II) complexes prepared
with copper acetate as metal precursors [Cu(L1)2] (C2)
and [Cu(L2)2] (C4) exhibited 1:2 molar ratios for metal:
ligand.
C, 55.80; H, 5.82; N, 9.32. Found (%): C, 55.82; H, 5.80;
N, 9.30. FT‐IR (cm−1): pyridine C=N (1563), >C=N‐
N=C < (1606), OH (3445), C‐O (1247). ΛM (CHCl3, mho
cm2 mol−1): 0.58. UV–Vis (CHCl3): λmax (nm), (εmax
(Lmol−1cm−1)): 280 (1,768.3), 390 (2,915.3), 414 (5774.9),
712 (73.22). EPR (g׀׀, g⊥, gav, Grnd. State, Geometry):
2
2
2.129, 2.074, 2.0923, dx ‐dy , Sq. Pyramidal.
C2: yield: 70%; anal. calcd for CuC42H52N6O4 (%): C,
65.60; H, 6.85; N, 10.93. Found (%): C, 65.58; H, 6.82; N,
10.93. FT‐IR (cm−1): pyridine C=N (1560), >C=N‐
N=C < (1606), OH (3442), C‐O (1253). ΛM (CHCl3, mho
cm2 mol−1): 25.6. UV–Vis (CHCl3): λmax (nm), (εmax
(Lmol−1cm−1)): 254 (777.6), 288 (627.8), 415 (791.0), 675
(575.2), 715 (125.5). EPR (g׀׀, g⊥, gav, Grnd. State, Geom-
2
etry): 2.0476, 2.1434, 2.1115, dz , Compressed Octahedral.
C3: yield: 80%; anal. calcd for Cu2C44H56N6O4Cl2 (%):
C, 56.70; H, 6.08; N, 9.03. Found (%): C, 56.72; H, 6.06;
N, 9.02. FT‐IR (cm−1): pyridine C=N (1568), >C=N‐
N=C < (1603), OH (3443), C‐O (1246), ΛM (CHCl3, mho
cm2 mol−1): 0.87. UV–Vis (CHCl3): λmax (nm), (εmax
(Lmol−1cm−1)): 288 (539.2), 393 (630.1), 414 (3844.0),
691 (98.76), 851 (30.55). EPR (g׀׀, g⊥, gav/giso, Grnd. State,
2
2
Geometry): 2.1748, 2.0759, 2.1089 (2.0823(RT)), dx ‐dy ,
Sq. Pyramidal.
C4: yield: 78%; m.p.: > 300°C; anal. calcd for
CuC44H56N6O4 (%): C, 66.31; H, 7.07; N, 10.58. Found
(%): C, 66.29; H, 7.08; N, 10.55. FT‐IR (cm−1): pyridine
C=N (1568), >C=N‐N=C < (1597), OH (3442), C‐O
(1251). ΛM (CHCl3, mho cm2 mol−1): 1.26. UV–Vis
(CHCl3): λmax (nm), (εmax (Lmol−1cm−1)): 253 (1410.8),
285 (1355.6), 383 (1850.4), 667 (266.93). EPR (g׀׀, g⊥,
3.2 | Molar conductivity measurements
The molar conductance values of complexes in methanol
and chloroform at concentration 10−3 M fall in the range
1–13 mho cm2 mol−1 (Table 1). These values are much
less than that expected for 1:1 electrolytes (65–90 mho
cm2 mol−1) and, hence, are feeble electrolytic in
nature.[20]
2
gav, Grnd. State, Geometry): 2.0475, 2.1685, 2.1282, dz ,
Compressed Octahedral.
3.3 | NMR studies
3 | RESULTS AND DISCUSSION
3.1 | Synthesis and characterization
1H‐NMR spectra of the common precursor of the
ligands L1H and L2H, i.e. 3,5‐di‐tert‐butyl‐2‐
hydroxybenzoylhydrazide 2 shows the resonance of
hydrazine‐NH2 proton at 3.85 ppm, ‐NH proton at 12.23
ppm, phenolic ‐OH proton at 8.1 ppm, aromatic protons
The synthetic protocol employed in the syntheses of
the copper complexes C1–C4 from the ligands L1H and
L2H is outlined in Scheme 2. The reaction of 3,5‐di‐tert‐
TABLE 1 Molar conductivity and electronic spectral data
butyl‐2‐hydroxybenzoylhydrazide
with
pyridine‐2‐
aldehyde and 2‐acetylpyridine formed the ligands L1H
and L2H, respectively, in good yields. The ligands L1H
and L2H on metallation reaction with copper (II) salts
of different anions in methanol at room temperature
yielded the Cu (II) complexes with the general formulae
[Cu2Cl2(L1)2] (C1), [Cu(L1)2] (C2), [Cu2Cl2(L2)2] (C3)
and [Cu(L2)2] (C4). Copper salts with various
counteranions like chloride, acetate, nitrate, sulphate,
phosphate and perchlorates were used to study their
Compound
λmax (nm)
Molar cond. ΛM
L1H
C1
211, 304, 340
–
208, 280, 390, 414, 712
210, 254, 288, 415, 675, 715
234, 268, 342
0.58
12.6
–
C2
L2H
C3
234, 288, 393, 414, 691, 851
253, 285, 383, 667
0.87
1.26
C4

HEGDE ET AL.
5 of 15
at 7.18 and 7.47 ppm, and tertiary butyl protons at 1.28
and 1.36 ppm, respectively. The other two precursors:
pyridine‐2‐aldehyde and 2‐acetylpyridine of ligand L1H
and L2H exhibit a singlet at 10.1 ppm for an aldehydic
proton and three proton singlets for acetyl protons at
2.729 ppm, respectively. These peaks shifted to 8.73 and
2.57 ppm in L1H and L2H, respectively, indicating the
successful formation of Schiff base ligands through the
imine linkage.[21] 1H‐NMR spectra of the ligand L1H
exhibited highly deshielded proton peaks at 15.63 and
12.64 ppm, and also some additional peaks even after
using re‐crystallized pure sample for the analysis. Careful
investigation of the spectra of the compound and the lit-
erature survey[22] concluded the presence of two inter‐
convertible E/Z geometrical isomers in the solution.
There are two ways that the Schiff base ligand could be
formed by imine linkage of the precursor 2 with 2‐
formylpyridine. Pyridine ring and the amide NH on the
same side of the imine bond constitutes the Z isomer,
and on the opposite side result in the E form.[22,23] Inter-
estingly, the Z isomer enables two intra‐molecular hydro-
gen bonds, one between the pyridine nitrogen and the
amide proton, and the other between the carbonyl oxygen
of the amide and the phenolic hydrogen. The effect of
these hydrogen bonds was reflected in the highly down-
field peaks for amide NH and C(2)‐OH at 15.63 and
12.64 ppm, respectively,[24–26] whereas in the E isomer
there is no scope for such hydrogen bonds, and these
peaks were found at 12.28 and 11.13 ppm, respectively,
as depicted in Scheme 3(a). (1H‐NMR spectra of ligand
precursor 2 and both ligands are provided as Supporting
information.) Further, the various additional peaks of
low intensities also confirm the presence of both the
mutually inter‐convertible isomers in the solution state
for L1H. The peaks due to NH and OH protons in the Z
isomer appeared as sharp peaks in contrast to their usual
broad nature. The probable reason for this would be the
intra‐molecular hydrogen bonding that checks their
chemical exchangeability.
The ligand L2H, however, exhibits clear NMR spec-
trum without any additional peaks, due to the more sta-
ble Z isomer than the E isomer wherein steric repulsion
between the bulky methyl group and the amidic proton
dominates as depicted in Scheme 3(b). The downfield
peaks at 15.93 and 12.80 ppm were authentically assign-
able again to the amide NH and phenolic C(2)‐OH pro-
tons, respectively. (The above hypothesis is further
supported by the X‐ray crystal structure of the ligand
L2H in the Z configuration, as detailed in Section 3.7.)
The aroyl hydrazone ligands L1H and L2H are poten-
tial NNO chelators, but the Z isomer is geometrically
unfavourable for coordination with the metal ions, hence
they must reorient to the E conformation during the com-
plexation as shown in Scheme 4. The absence of any
SCHEME 3 Schematic representation
of (a) inter‐convertability of Z and E
isomers of L1H and (b) the steric
repulsion in E isomer of L2H resulting in
the more stable Z isomer and their
1
corresponding H‐NMR shift of NH and
OH protons

6 of 15
HEGDE ET AL.
SCHEME 4 Schematic representation of the reorientation of ligands during complexation
additional small intensity peaks in 1H‐NMR spectra of the
zinc (II) complexes of L1H as well as L2H also provided
supporting evidence that the ligands L1H (E/Z isomeric
mixture) and L2H (Z isomer) were all converted into
the E isomeric form during the complexation (1H‐NMR
spectra of ligands and their zinc complexes were provided
as Supporting information).
completely absent in both the ligands,[28,29] indicating
the successful formation of the Schiff base ligands
through the imine (>C=N) bond.
The IR spectral observation stands complementary
with the NMR spectral interpretations. The presence of
weak peaks at about 3288 and 1683 cm−1 in both the
ligands were assigned to >NH and > C=O groups of the
amide, respectively. The strong and sharp peaks at about
3426 cm−1 that appeared in both the ligands were
assigned to the phenolic –OH under the intra‐molecular
hydrogen bonding interaction with the carbonyl group
of the amide.[30,31] All these observations further support
the Z isomeric forms of both the ligands in the solid state.
The Z isomeric hydrazone keto form of both the
ligands in the solution undergoes rearrangement to the
E conformation, followed by tautomerization to the
diimino enol forms, in the presence of metal salts during
complexation. Disappearance of the two amide bands in
all the complexes confirms the transition to diimino enol
tautomer in the complexes. The diimino enolic form of
the ligand moieties in the complexes enjoys further stabi-
lization through the cooperative intra‐molecular hydro-
gen bonding between the uncoordinated diimine N with
C2‐OH, as depicted in Scheme 4.[32] This observation
was further supported by the fact that the sharp OH
bands at about 3426 cm−1 in the ligands were broadened
in all the complexes.
The 13C‐NMR spectrum of L2H was in agreement with
the 1H‐NMR data, and all the signals were suitably
assigned to the respective carbon atoms of the ligand mol-
ecule. However, 13C‐NMR spectra of L1H, like its proton
NMR, was found to contain many additional peaks of low
intensities making it difficult for the assignment. But, this
observation further confirms the presence of both the E/Z
geometrical isomers in the solution. Peaks at 149 and 153
ppm were due to RC(8) = N azomethine carbon atoms in
the ligands, respectively. The appearance of these two sig-
nals is the major supporting evidence for the successful
formation of ligands L1H and L2H. The signals of 13C‐
NMR spectra of L1H and L2H ligands observed at 159
and 169 ppm were assigned to the ‐HN‐C(7) = O carbon
atoms in the two ligands, respectively. Other aromatic
and aliphatic carbons were observed in the expected
region, and are detailed in the Experimental section
(13C‐NMR spectra of ligand precursor 2, ligands and
their zinc complexes were provided as Supporting
information).
In order to satisfy the primary valency of the metal
ion during the complexation, the ligands sacrifice the
enolate proton to coordinate through enolate oxygen
anion.[33] The sharp azomethine >C=N‐ bands at about
1630 cm−1 in both the ligands shifted to lower frequen-
cies by about 25–30 cm−1[34] in all the complexes,
confirming the formation of azine group and coordination
through one of its nitrogens.[35] The bands at 1588 and
1591 cm−1 assigned to aromatic pyridine C=N absorp-
tions in both the ligands shift to a lower frequency by
10–15 cm−1 in all the complexes, suggesting complexation
through this nitrogen.[36] Hence, the IR spectra support
the behaviour of both the ligands as tridentate; utilizing
pyridine‐N, azine‐N and diimino enolate‐O as donor sites.
3.4 | Infrared spectral studies
The FT‐IR spectral data for the free ligands and their
complexes are detailed in the Experimental section. The
condensation of the aroyl hydrazide with 2‐formyl
pyridine/2‐acetyl pyridine leading to the formation of
the imine linking group and their coordination behaviour
were supported in the IR spectral assignment. The FT‐IR
spectra of both the ligands exhibit typical intense bands
centred at about 1630 cm−1, which were assigned to
azomethine functionality,[27] and the peculiar –NH bend-
ing absorption in the precursor 2 found at 1524 cm−1 is

HEGDE ET AL.
7 of 15
The spectra are rather complex in the region below
500 cm−1, where the various M‐L bond stretching vibra-
tions are often found in combination with other bands
(the IR spectra of ligand precursor 2, ligands and their
complexes are provided in the Supporting information).
(II) complexes cannot exist. The t2geg separation in a reg-
ular octahedral copper (II) complex varies from about 13
000 cm−1 to about 18 000 cm−1
.
For the copper (II) complexes, C2 and C4 in chloro-
form (10−3 M solution), the d‐d bands were observed in
the regions 666–720 nm, i.e. 15 000–13 800 cm−1, which
2
2
could be assigned to the T2g to Eg transition of an octa-
2
2
hedral geometry. However, the T2g to Eg states of the
octahedral Cu (II) ion (d9) split under the influence of
the tetragonal distortion, and the three transitions
3.5 | Electronic spectral studies
The electronic spectra of the ligands and their copper
complexes were recorded in chloroform, and the data
are summarized in Table 1. Both the ligands exhibit
UV–Vis absorption bands at about 211–230, 270–304
and 340–342 nm. The intense bands at about 211 and
234 nm in the ligands, which almost remain unchanged
in the spectra of their complexes, were due to solvent
absorptions. The ligand bands at about 270–304 and
340–342 nm were due to the π → π* transitions of the
organic moieties with various π systems.[37,38] The ligands
show broad and intense bands at about 304–342 nm that
were assigned to π → π* transition of azo >C=N‐NH‐
functional group.[39] These bands in all the complexes
exhibit red shift due to the tautomerization of azo to
azine moiety >C=N‐N=C<, and coordination of one of
the azine nitrogens to the metal centres.
2
2
2
2
2B1g2Eg, B1g B2g and B1g A1g are expected.[42] But, such
complexes exhibit[43] a broad band with or without the
shoulder between 500 and 770 nm depending upon the
strength of the in‐plane and axial ligands. It is concluded
that all the three transitions will be within this broad
envelope. The spectra of copper (II) complexes C2 and
C4 exhibit broad d‐d absorption bands with λmax at 675
and 667 nm (14 815, 14 992 cm−1), with εmax values of
575.2 and 266.93 indicative of a distorted octahedral
system.[44]
Broad asymmetric peaks at about 712 nm, with a low‐
energy shoulder band, have been observed for Schiff base
binuclear copper (II) complexes with square‐pyramidal
geometries.[45–47] The bridged di‐copper bivalent com-
plexes generally show an LMCT band in the near‐UV
region at about 414 nm[48,49] with εmax values of 5774.9
3844.0 for [Cu2Cl2(L1)2] (C1) and [Cu2Cl2(L2)2] (C3)
complexes, which were assigned with the square pyrami-
dal geometry.[50] The representative spectra of ligand
L2H and complex C3 are shown in Figure 1. The remain-
ing UV–Vis spectra are provided in the Supporting
information.
The electronic spectra of copper (II) complexes exhib-
ited λmax values at about 390, 414 and 690–712 nm in all
the complexes, which were the electronic transitions
influenced by the coordination bond. The electronic spec-
tra of the copper complexes were observed as three main
transitions. The spectra of the complexes also show mod-
erate intense bands at 30 000–35 000 cm−1, assignable to
nitrogen‐centred ligand to metal charge transfer (LMCT)
transitions from the coordinated unsaturated ligand to
the metal ion.[40] The bands at higher energies at about
~30 000 cm−1 are associated with the azomethine of azine
group shifts to longer wavelength, indicating the coordi-
nation of azomethine nitrogen to copper.[41] The ground
state in an octahedral field is unstable due to the Jahn–
3.6 | EPR spectral studies
The EPR spectra are recorded for copper complexes in
powder form, and the results are given in Table 2. G =
2.303 for the dimeric complex C3, the value of which is
less than 4 hence, a considerable exchange interaction is
2
Teller distortion; hence, Eg of regular octahedral copper
FIGURE 1 Representative electronic spectrum of ligand L2H and its complex C3

8 of 15
HEGDE ET AL.
TABLE 2 EPR data
Comp.
g׀׀
g⊥
gav/giso
μ
Ground state
Geometry
2
2
C1
C2
C3
C3
C4
2.129
2.0476
2.1748
–
2.074
2.1434
2.0759
–
2.0923
1.812
1.829
1.826
1.803
1.843
dx ‐y
Square pyramidal
2
2.1115
dz
Compressed octahedral
Square pyramidal
2
2
2
2.1089
dx ‐y
2
2.0823(RT)
2.1282
dx ‐y
Square pyramidal
2
2.0475
2.1685
dz
Compressed octahedral
indicated in this solid complex. The g׀׀ is the moderately
sensitive function of the metal–ligand covalency.[51] The
ionic environment is indicated when g׀׀ is 2.3 or larger,
and it is less than 2.3 for more covalent environments.
The ground state orbital and the respective geometry for
all the complexes were tabulated based on the corre-
sponding ‘g’ values. The g׀׀ values < 2.3 for all the copper
complexes indicate the larger percentage of covalency in
their metal–ligand bonds. The shape of the EPR graph
indicates that these complexes may have either a square
pyramidal or elongated octahedral geometry. The lowest
gav value of C1 and C3 compared with other complexes
is attributed to the bis μ chloro bridge present in these
bimetallic square pyramidal complexes. The C3 complex
showed giso, when the spectrum was taken for the sample
in the powdered form at room temperature. However, the
spectrum taken at 77 K for this complex dissolved in
DMSO appears to exhibit anisotropy with the two ‘g’
values, as depicted in Figure 2. A similar observation
was recorded by Roy et al.[52]
as from the single‐crystal XRD analysis. The ligation of
L2H was tried with copper salts of various anions like
chloride, acetate, nitrate, perchlorate, phosphate and sul-
phate to look for the subsequent effect on complexation.
The chloride salt exhibited a normal EPR spectrum; how-
ever, acetate and all other salts exhibited the compressed
octahedral geometry. The EPR spectra of all of them
appear similar with the same g׀׀, g⊥ and gav values, so
as their IR spectra also overlap with each other. This
was the clear indication that anionic species other than
chloride neither entered the coordination sphere, nor in
any way were retained in the complex compound.
Thus, this indicated no role of them in the coordination
(the EPR spectra of the complexes are provided in the
Supporting information).
3.7 | Thermal analysis
All the complexes were studied for their thermal behav-
iour over the temperature range of 25–1000°C under
ambient atmosphere (the thermograms of the ligands
and the representative complexes were provided as
Supporting information).
The X‐band EPR spectrum of C4 was found to be of
the inverse type, and the z‐in compressed octahedral
geometry was assigned based on the ‘g’ values, as well
Thermal studies of both the ligands showed weight
loss in the temperature range of 130–150°C amounting
to 2.3–5.7% due to the loss of lattice‐held methanol mole-
cules. Further, both the ligands were thermally stable up
to about 270°C, and then L1H and L2H underwent com-
plete degradation within 400°C and 500°C, respectively.
Thermal studies of C1 indicated that the complex was
stable up to 273°C after the loss of lattice‐held solvent
molecule during 37–65°C amounting to 6.7%. The
observed weight loss of 82.4% from 273 to 307°C corre-
sponds to the loss of arolhydrazone ligand fragment
(C42H52N6O4Cl3−). The remaining part Cu2Cl3+ gradually
loses chlorine and finally oxidized to cupric oxide from
307 to 1000°C. The thermal studies of C2 indicated that
the complex was very stable up to 354°C. Then the ther-
mogram exhibited sharp weight loss of 79.2% up to
366°C due to the loss of two ligand fragments
FIGURE 2 X‐band electron paramagnetic resonance (EPR)
spectrum of complex C3 (a) in the solid state at room
temperature, and (b) in DMSO solution at 77K
3−
(C42H52N2). Finally, the remaining fragment CuN4O2

HEGDE ET AL.
9 of 15
decomposed to stable cupric oxide. The theromogram of
complex C3 indicated the weight loss of 2.7% from 49 to
72°C indicating the loss of lattice‐held solvent molecule,
and then the complex was stable up to 317°C. The weight
loss of 76.9% from 317 to 329°C amounts to the loss of
coordinated ligand part (C44H56N6O42-), leaving behind
39% amounted to another ligand fragment of C22H28.
The remaining metal fragment of CuN2O4 gradually
decomposed to the stable copper oxide as exhibited by
the plateau.
2+
the Cu2Cl2 fragment. Then from 329°C onwards, the
3.8 | Single‐crystal X‐ray diffraction
studies
thermogram showed gradual weight loss due to chlorine
molecule, and the formation of stable refractory copper
oxide compound. The thermogram curve for C4 indicated
stability up to 273°C, and then decomposed in three
sharp intermediate steps. The weight loss of 41.9% in
the first step from 273 to 276°C is near to the calculated
mass loss of one of the coordinated ligand fragments
(C22H28N3), leaving two oxygen atoms intact with the
remaining part. In the second step, the weight loss of
The structures of the ligand L2H and its copper com-
plexes C3 and C4 were unambiguously established by
the XRD studies. Summaries of the crystallographic data,
bond lengths and bond angles of the compounds L2H, C3
and C4 are shown in Tables 3 and 4. ORTEP representa-
tions of L2H, C3 and C4 showing 50% displacement
ellipsoids are shown in Figures 3, 4 and 5, respectively.
TABLE 3 Crystal data and structure refinement details of the ligand L2H and the complexes, C3 and C4
Crystal data
L2H
C3
C4
Empirical formula
C22H29N3O2
367.49
C44H56Cl2Cu2N6O4
930.96
C44H56CuN6O4
796.49
Formula weight
Temperature/K
293
293(2)
296(2)
Crystal system
Orthorhombic
Pbca
Monoclinic
P21/c
Orthorhombic
Pnna
Space group
a/Å
8.3683(15)
15.211(3)
33.321(6)
90.00
16.2026(7)
9.5114(5)
15.7038(7)
90.00
10.4172(7)
33.818(3)
12.0400(9)
90.00
b/Å
c/Å
α/°
β/°
90.00
113.256(2)
90.00
90.00
γ/°
90.00
90.00
Volume/Å3
4241.6(7)
8
2223.47(10)
2
4241.6(6)
4
Z
ρ
calcg/cm3
1.151
1.390
1.247
μ/mm−1
0.07
2.668
1.11
F (000)
1584
972.0
1692.0
Crystal size/mm3
0.24 × 0.21 × 0.18
MoKα (λ = 0.71070 Å)
4.88 to 47.7
0.29 × 0.25 × 0.22
CuKα (λ = 1.54178 Å)
12.0 to 129.0
0.23 × 0.11 × 0.09
CuKα (λ = 1.54178 Å)
11.6 to 128.8
Radiation
2θ range for data collection/°
Index ranges
−9 ≤ h ≤ 9, −17 ≤ k ≤ 17,
−37 ≤ l ≤ 37
−17 ≤ h ≤ 18, −11 ≤ k ≤ 11,
−18 ≤ l ≤ 18
−11 ≤ h ≤ 11, −39 ≤ k ≤ 39,
−13 ≤ l ≤ 13
Reflections collected
14 321
13 513
20 099
Independent reflections
Data/restraints/parameters
Goodness‐of‐fit on F 2
3273 (Rint = 0.036)
1882/0/1
3651 (Rint = 0.039)
3651/0/269
3483 (Rint = 0.145)
3483/0/288
0.72
1.05
1.04
Final R indexes [I ≥ 2σ (I)]
Final R indexes (all data)
Largest diff. peak/hole/e Å−3
R1 = 0.036, wR2 = 0.148
R1 = 0.036, wR2 = 0.148
0.79/−0.30
R1 = 0.039, wR2 = 0.101
R1 = 0.039, wR2 = 0.101
0.54/−0.46
R1 = 0.066, wR2 = 0.202
R1 = 0.1079, wR2 = 0.2021
0.36/−0.49

10 of 15
HEGDE ET AL.
TABLE 4 Selected bond lengths (Å) and angles (o) of complexes C3 and C4
L2H
C3
C4
Bond lengths (Å)
Bond lengths (Å)
Bond lengths (Å)
C6‐N2
1.2963(1)
1.3553(2)
1.4845(2)
1.3261(2)
1.3771(2)
0.880
Cu1‐N2
1.926(2)
1.971(16)
2.015(2)
2.2216(6)
2.7446(6)
1.280(3)
1.338(3)
1.363(3)
Cu1‐N21
1.963(3)
1.963(3)
2.147(3)
2.185(4)
1.263(5)
1.344(5)
1.373(5)
1.476(6)
C5‐N1
Cu1‐O1
Cu1‐N2
C5‐C6
Cu1‐N1
Cu1‐O11
Cu1‐N1
C1‐N1
Cu1‐Cl1
Cu1‐Cl11
O1‐C7
N2‐N3
O1‐C7
N3‐H30
C7‐O1
N3‐C7
1.2385(2)
1.3502(2)
N1‐C1
N3‐N2
C13‐O2
Bond angles (o)
N1‐C5
C8‐C7
Bond angles (o)
Bond angles (o)
C6‐N2‐N3
N3‐C7‐C8
C7‐C8‐C13
C8‐ C7‐ N3
H30‐N3‐C7
C7‐C8‐C9
117.893(11)
116.190(10)
118.195(9)
116.190(10)
121.8
N2‐Cu1‐O1
N2‐Cu1‐N1
O1‐Cu1‐N1
N2‐Cu1‐Cl1
O1‐Cu1‐Cl1
N1‐Cu1‐Cl1
N1‐C1‐C2
80.02(7)
80.17(8)
159.52(8)
174.10(6)
99.56(5)
99.60(6)
121.9(2)
N21Cu1N2
N21Cu1O1
O11Cu1O1
N2Cu1N1
C7O1Cu1
C1N1C5
174.9(2)
100.07(13)
97.62(17)
77.08(14)
109.7(3)
119.8(4)
116.0(4)
122.855(8)
121.145(8)
C9‐C10‐C18
N3C7C8
FIGURE 3 ORTEP projection of L2H
showing 50% probability ellipsoids
The asymmetric unit of L2H crystallized in an ortho-
rhombic crystal system with no crystal‐held solvent or
water molecules. The ligand structure maintains overall
co‐planarity with only the t‐butyl group popping out of
the plane of the molecule. With respect to the azomethine
module (C6 = N2), which averages to 1.294(5) Å, the con-
figuration is Z, with the highest priority groups, pyridine
and the amide functionality in the cis‐arrangement, that
is on the same side of this azomethine linkage. This con-
figuration is stabilized by the strong intra‐molecular
hydrogen bonding interaction between pyridine nitrogen,
N1 and the proton of amidic linkage H30, N3‐H30··· N1,
N3‐H30 averaging to 2.616 Å and H31···N1 averaging to
1.913 Å. The O2‐H20···O1 hydrogen bonding is character-
ized by O2‐H20 length of 0.82 Å and H20···O1 length
averaging to 1.76 Å.
The X‐ray structure of complex C3 shows that two
square planar copper (II) centres, joined by the two bridg-
ing chloride ions in an end‐to‐end fashion, share the axial
and equatorial positions, respectively.[53] Both the metal

HEGDE ET AL.
11 of 15
FIGURE 4 ORTEP projection of C3 showing 50% probability ellipsoids
FIGURE 5 ORTEP projection of C4 showing 50% probability ellipsoids
centres have penta coordination with the distorted square
pyramidal geometry using an N2OCl2 coordination
sphere provided by a tridentate ligand in a meridional
fashion with a dihedral angle of 88.64o, using pyridine‐
N, azine‐N and diimino enolate‐O and two bridging chlo-
ride ions, respectively. The NNO donor sites of the
tridentate ligand coordinate the Cu (II) centres to form
two five‐membered C2N2Cu and CN2OCu chelate rings,
with bite angles of 80.17(8)o and 80.02(7)o, respectively,
in both halves of the complex. The deviation of both
Cu(1) atoms from the coordinate plane [the least squares
plane composed of Cl(l), O(1), N(2) and N(1)] is 0.107 Å.
The Cu1....Cu1 distance is 3.45(5) Å. The equatorial Cu1–
Cl1 [2.2216(6) Å] distance is much smaller than the axial
Cu1–Cl2 [2.7446(6) Å] distance, clearly indicating the
distorted as well as compressed square pyramidal geome-
try around the metal centre. The equatorial Cu1–Cl1
[2.2216(6) Å] bond distance around both the metal cen-
tres is comparable to those of similarly reported com-
plexes,[54] but this distance is longer than Cu1–N1
[2.015(2) Å], Cu1–N2 [1.926(2) Å] and Cu1–O1
[1.9710(16) Å]. The Cu1–Cl2–Cu2 angle is found to be
87.40(2)o.
The X‐ray structure of complex C4 shows a distorted
octahedral structure wherein the Cu (II) metal ion centre
is surrounded by an N4O2 coordination sphere, provided

12 of 15
HEGDE ET AL.
by a tridentate ligand in a meridional fashion with a dihe-
dral angle of 88.74o using pyridine‐N, azine‐N and diimino
enolate‐O as donor sites. The NNO donor sites of the
tridentate ligand coordinate the Cu (II) centre to form
two five‐membered C2N2Cu and CuN2CO chelate rings,
with bite angles of 77.08(14)o and 76.53(12)o, respectively,
indicating distortion from an ideal octahedral geometry.
The metal centre is sited in an axially distorted compressed
octahedral geometry; probably due to Jahn–Teller distor-
tion. The C‐O bond distance of 1.263(5) Å supports the
existence of coordination via enolate oxygen to the metal
centre. The Cu‐N (py) bond and Cu‐O(1) (carboxyl) bonds
[2.185(4) Å and 2.147(3) Å] are significantly longer than
the Cu‐N(2) [1.963(3) Å], although the latter is formed
via deprotonation. This difference can be attributed by
the bis (chelating) mode of the ligand in which the
Cu–N/O bonds (pyridine nitrogen) and carbonyl oxygen
(O‐carboxyl) appear to be shared by two five‐membered
chelate rings. Similar observations were seen in the
complexes having similar coordination mode.[55] In the
extended crystal structures of both the complexes,
the azine (diimino) enol tautomeric form of the ligand is
further supported by the existence of cooperative intra‐
molecular hydrogen bonding between azine nitrogen and
hydroxyl ‐OH group.
and 1867983, respectively. The supplementary crystallo-
graphic data of these compounds can be obtained free
of charge via https://www.ccdc.cam.ac.uk/structures/.
3.9 | Biological assay
All the synthesized compounds were evaluated for
their antimicrobial activity against Staphylococcus aureus,
a gram‐positive bacterium, and gram‐negative Escherichia
coli pathogens using micro‐broth dilution method. Cipro-
floxacin is used as the standard drug to compare the
activity of the samples and the minimum inhibitory
concentration (MIC) of which for both the pathogens is
2 μg mL−1. The potency of ligands and their complexes
was studied by comparing the turbidity[56] formed with
that of the standard drug on two bacterial strains, and
the result is shown in Table 5. The ligand L2H and all
its copper complexes exhibited better activity even than
the ‘Ciprofloxacin' control for the S. aureus microorgan-
ism. However, for E. coli, except complex C3, the rest
of the compounds were better than the control.
The ligand L1H in the E/Z isomeric forms and its com-
plexes showed different antimicrobial behaviour against
gram‐positive and gram‐negative bacteria, respectively.
L1H and C1 were sensitive to S. aureus, only at higher
concentrations, i.e. at 12.5 and 25 μg mL−1, respectively,
whereas C2 was sensitive at 0.8 μg mL−1 concentration.
However, L1H and both of its complexes were very sensi-
All the crystal structures were deposited to Cambridge
Crystallographic Data Centre via the joint CCDC/FIZ
Karlsruhe deposition service. The crystal structures of
the ligands L2H [Cu2Cl2(L2)2] (C3) and [Cu(L2)2] (C4)
were assigned the CCDC numbers as 1884153, 1867982
tive to E. coli at very low concentration of 0.4 μg mL−1
.
TABLE 5 Antimicrobial activity report
100 μg
50 μg
25 μg
12.5 μg
6.25 μg
3.12 μg
1.6 μg
0.8 μg
0.4 μg
0.2 μg
Samples
mL−1
mL−1
mL−1
mL−1
mL−1
mL−1
mL−1
mL−1
mL−1
mL−1
Sl. no.
Staphylococcus aureus
1
2
3
4
5
6
L1H
C1
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
R
S
S
S
S
R
R
S
R
R
S
R
R
S
R
R
S
R
R
R
S
R
R
R
R
R
R
C2
L2H
C3
S
S
S
S
S
S
S
S
S
C4
S
S
S
S
S
Escherichia coli
1
2
3
4
5
6
L1H
C1
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
R
S
S
S
S
S
R
S
S
S
S
S
R
S
R
R
R
R
R
R
C2
L2H
C3
C4
S, Sensitive; R, Resistant.

HEGDE ET AL.
13 of 15
TABLE 6 Anti‐tuberculosis activity report
Sl. no. Samples 100 μg mL−1 50 μg mL−1 25 μg mL−1 12.5 μg mL−1 6.25 μg mL−1 3.12 μg mL−1 1.6 μg mL−1 0.8 μg mL−1
1
2
3
4
5
6
L1H
C1
S
S
S
S
S
S
R
S
S
S
S
S
R
S
S
S
S
S
R
S
R
R
R
S
R
R
R
S
R
R
R
R
S
R
R
R
R
R
R
C2
R
S
L2H
C3
S
S
S
C4
S
S
S
R
S, Sensitive; R, Resistant.
The synthesized compounds were also evaluated for
their anti‐mycobacterial activities against Mycobacterium
tuberculosis (H37 RV strain): ATCC No‐27294, using
the Microplate Alamar Blue Assay (MABA) method.[57]
The results of the analysis were shown in Table 6. The
MIC of ligand L2H was found to be 3.125 μg mL−1 and is
as good as three controls, i.e. pyrazinamide (3.125 μg mL
(M:L) stoichiometry for [Cu2Cl2(L1)2] (C1) and
[Cu2Cl2(L2)2] (C3), and 1:2 for [Cu(L1)2] (C2) and
[Cu(L2)2] (C4). Thus, from the physico‐chemical investi-
gation, it was observed that the coordination mode of
the ligands was of mono basic tridentate in all the
complexes. The two distinct dichlorido‐bridged dinuclear
copper (II) complexes, i.e. [Cu2Cl2(L1)2] (C1) and
[Cu2Cl2(L2)2] (C3) adopted distorted square pyramidal
geometries. However, the complexes derived from Cu
(II) acetate precursors, i.e. [Cu(L1)2] (C2) and [Cu(L2)2]
(C4) adopted the six coordinated distorted octahedral
geometries.
Although the copper (II) precursors with various coun-
ter ions like chloride, acetate, nitrate, sulphate, phosphate
and perchlorates were tried to study their effect on the
complexation, only the chlorine atoms from the metal
salts exhibited their role in the complex as bridging the
two square pyramidal units. However, the rest of the
counter ions during the complexation escaped from
the complex, leading to the formation of the same octahe-
dral complex without any diverse products. The synthe-
sized copper complexes were evaluated for anti‐
microbial and anti‐tuberculosis activity. Anti‐tuberculosis
activity revealed an MIC value of 1.6 μg mL−1 for C3 and
3.125 μg mL−1 for C4, which was almost four and two
times more active than standard streptomycin (6.25 μg
mL−1), and two times more active than and as active as
the pyrazinamide and ciprofloxacin (3.125 μg mL−1 each)
standards, respectively. Also, the ligand L2H and all its
copper complexes were highly active and even better than
the ‘Ciprofloxacin’ control for the S. aureus microorgan-
ism, but for E. coli, except the C3 complex, the rest of
the compounds demonstrated activities better than the
control. L1H and both of its complexes were very sensi-
tive to E. coli at low concentration of 0.4 μg mL−1; how-
ever, only C2 was sensitive at 0.8 μg mL−1 concentration
against S. aureus. The activities demonstrated by the
synthesized compounds are encouraging and illustrate
the prospective of these copper complexes as potential
chemotherapeutic drugs as anti‐microbial and anti‐
−1), ciprofloxacin (3.125 μg mL−1
) and streptomycin
(6.25 μg mL−1). The MIC value of 1.6 μg mL−1 for C3 and
3.125 μg mL−1 for C4, which are almost four and two times
more active than standard streptomycin (6.25 μg mL−1
)
and two times more active than and as active as the
pyrazinamide and ciprofloxacin (3.125 μg mL−1 each)
standards, respectively.
The MIC values of L1H and its complexes were again
different from others, as neither the ligand nor its
complexes C1 and C2 exhibited better sensitivity against
M. tuberculosis. The ligand was sensitive only at very high
concentration of 100 μg mL−1, whereas the complexes C1
and C2, even though they exhibited better sensitivities
than ligand, they were not better than any of the three
standard controls.
4 | CONCLUSION
The copper (II) complexes of two new ligands L1H and
L2H: 3,5‐di‐tert‐butyl‐2‐hydroxybenzoylhydrazones of 2‐
formylpyridine and 2‐acetylpyridine were synthesized in
good yields. The ligand L1H exists as inter‐convertible
E/Z geometric isomeric forms, whereas the ligand L2H
exists exclusively as a Z isomer due to steric reasons.
But both the ligands L1H and L2H undergo transforma-
tion to the E form in order to coordinate to the Cu metal
centre. Further, the ligands bind the Cu (II) ion through
the pyridine‐N, azine‐N and diimime enolate‐O coordina-
tion sites in the tridentate manner. The various spectro‐
analytical techniques, in addition to the single‐crystal
X‐ray diffraction studies, assisted in deciding the molecu-
lar structures of the copper complexes indicating the 2:2

14 of 15
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Ellipsoid Plot Program for Crystal Structure Illustrations, Oak
Ridge National Lab, USA: N.p. 1996 https://doi.org/10.2172/
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The authors are thankful to USIC, Karnatak University,
Dharwad, India, for providing spectral facilities. Record-
ing of NMR from IISc‐Bangalore, EPR from SAIF IIT
Bombay, biological activity studies from Maratha
Mandal's Institute of Dental Science & Research Centre,
Belgaum, and SXRD analysis from Mysore University
are all gratefully acknowledged. One of the authors
(Ganesh S. Hegde) is thankful to the University Grants
Commission, New Delhi (U.G.C.) for providing financial
assistance under the Minor Research Project program
with the UGC approval Letter No. MRP(S)‐0475/13‐14/
KAKA089/UGC‐SWRO and M. E. S., M. M. Arts and
Science College, Sirsi, Uttara Kannada, Karnataka, India,
for the basic research facilities, respectively.
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Ganesh S. Hegde https://orcid.org/0000-0003-4989-2487
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How to cite this article: Hegde GS, Netalkar SP,
Revankar VK. Copper (II) complexes of 3,5‐di‐tert‐
butyl‐2‐hydroxybenzoylhydrazones of 2‐
formylpyridine and 2‐acetylpyridine, with
tautomeric azine‐scaffold‐based architecture:
Synthesis, crystal structures, the effect of
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microbial and anti‐tuberculosis evaluation. Appl
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