Synthesis, potent anti-TB activity against M. tuberculosis ATTC 27294, crystal structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole derivatives

Article abstract of DOI:10.1016/j.molstruc.2018.10.030

The synthesis, anti-TB activity, crystal structures and ligand ability of a number of 2-arylidene-benzylidenehydrazinylbenzothiazole derivatives, 1, have been investigated. The compounds 1 were obtained from 2-hydrazinobenzothiazole and substituted benzaldehydes in refluxing methanol in yields, after recrystallisation, of 55–75%. The crystal structure determination of compounds, 1e (aryl = 4-MeOC₆H₄), 1h (aryl = pyridin-2-yl), 1f (aryl = 2-HO-5-MeC₆H₃) revealed amino forms, whereas an imino form was found for 1f (aryl = 2-HO-4-MeOC₆H₃). Despite the different tautomeric forms of 1e and 1h, the two compounds have similar cell dimensions and furthermore their intermolecular interactions combine to form similar sub-structures. Pairs of N–H?N hydrogen bonds and π···dπ stacking interactions produce dimers in all compound. The compounds with the best anti-mycobacterial activity were found to be 1c (aryl = 2-O₂NC₆H₄), 1d, (aryl = 2-HOC₆H₄), 1e and 1h, all having superior activities to that of the standard drug, ethambutol. Moreover two of these compounds have the capacity to act as tridentate ligands, namely 1d [a potential ONN chelator] and 1h [a potential NNN chelator]. Compound 1d (HL) acts as a tridentate O,N,N-donor to Cu^(II) in forming the dimeric octahedral complex{[(L) (H₂O)Cu][O₃SCF₃]}₂, 3, from Cu^{(II) (}O₃SCF₃)₂ in moist MeOH. The monomeric square-pyramidal [(L) (H₂O)Cu][O₃SCF₃], with an axial OS(O₂)CF₃ ligand and equatorial H₂O ligand, dimerizes through extensive π···π interactions involving two complete planar L-Cu fragments. The dimers are linked into a three dimensional array by O–H?O and N–H?O hydrogen bonds and by further π···π interactions. Complex 3, while still very active, has only about 40% of the activity of its ligand against M. tuberculosis ATTC 27294.

Full text of DOI:10.1016/j.molstruc.2018.10.030

Accepted Manuscript
Synthesis, potent anti-TB activity against M. tuberculosis ATTC 27294, crystal
structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole
derivatives
AlessandraC. Pinheiro, MarcusV.N. de Souza, MariaC.S. Lourenço, Cristiane F. da
Costa, Thomas C. Baddeley, John N. Low, SolangeM.S.V. Wardell, James L. Wardell
PII:
S0022-2860(18)31215-8
DOI:
https://doi.org/10.1016/j.molstruc.2018.10.030
MOLSTR 25759
Reference:
To appear in: Journal of Molecular Structure
Received Date: 29 June 2018
Revised Date: 10 October 2018
Accepted Date: 10 October 2018
Please cite this article as: A. Pinheiro, M.N. de Souza, M.S. Lourenço, C.F. da Costa, T.C. Baddeley,
J.N. Low, S.S.V. Wardell, J.L. Wardell, Synthesis, potent anti-TB activity against M. tuberculosis
ATTC 27294, crystal structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole
derivatives, Journal of Molecular Structure (2018), doi: https://doi.org/10.1016/j.molstruc.2018.10.030.
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ACCEPTED MANUSCRIPT
Synthesis, potent anti-TB activity against M. tuberculosis ATTC 27294, crystal
structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole
derivatives.
1
1
2
Alessandra C. Pinheiro , Marcus V. N. de Souza , Maria C. S. Lourenço ,
1
3
3
Cristiane F. da Costa , Thomas C. Baddeley, John N. Low, Solange M.S. V.
4
1,3*
Wardell, James L. Wardell
1
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos,
1041-250, Rio de Janeiro, RJ, Brazil, Fundação Oswaldo Cruz, Instituto Nacional de
2
2
Infectologia Evandro Chagas, Departamento de Bacteriologia, 21045-900, Manguinhos,
3
Rio de Janeiro, Brazil, Department of Chemistry, University of Aberdeen, Old
4
Aberdeen, AB 24 3 UE, Scotland, UK, . CHEMSOL, 1 Harcourt Road, Aberdeen AB5
5
NY, Scotland, UK.
Abstract
The synthesis, anti-TB activity, crystal structures and ligand ability of a number of
2
-arylidene-benzylidenehydrazinylbenzothiazole derivatives, 1, have been investigated.
The compounds 1 were obtained from 2-hydrazinobenzothiazole and substituted
benzaldehydes in refluxing methanol in yields, after recrystallisation, of 55 to75%. The crystal
structure determination of compounds, 1e (aryl = 4-MeOC H ), 1h (aryl = pyridin-2-yl), 1f (aryl
6
4
=
2-HO-5-MeC H ) revealed amino forms, whereas an imino form was found for 1f (aryl = 2-
6 3
HO-4-MeOC H ). Despite the different tautomeric forms of 1e and 1h, the two compounds have
6
3
similar cell dimensions and furthermore their intermolecular interactions combine to form
similar sub-structures. Pairs of N—H···N hydrogen bonds and π---π stacking interactions
produce dimers in all compound.The compounds with the best anti-mycobacterial activity were
found to be 1c (aryl = 2-O NC H ), 1d, (aryl = 2-HOC H ), 1e and 1h, all having superior
2
6
4
6
4
activities to that of the standard drug, ethambutol. Moreover two of these compounds have the
capacity to act as tridentate ligands, namely 1d [a potential ONN chelator] and 1h [a potential
(II)
NNN chelator]. Compound 1d ( HL) acts as a tridentate O,N,N-donor to Cu in forming
(
II)
the dimeric octahedral complex{[(L)(H O)Cu][ O SCF ]} , 3, from Cu (O SCF ) in
2
3
3
2
3
3 2
moist MeOH. The monomeric square-pyramidal [(L)(H O)Cu][ O SCF ], with an axial
2
3
3
OS(O )CF ligand and equatorial H O ligand, dimerizes through extensive π···
π
2
3
2
interactions involving two complete planar L-Cu fragments. The dimers are linked into
a three dimensional array by O—H···O and N—H···O hydrogen bonds and by further
1

ACCEPTED MANUSCRIPT
π···π interactions. Complex 3, while still very active, has only about 40% of the activity
of its ligand against M. tuberculosis ATTC 27294
-----------------------------------------------
.
-
Keywords: 2-Arylidenehydrazinylbenzothiazole derivatives: Crystal structure
determinations; Anti-TB activity; Copper complex; Imino/amino tautomers.
1
. Introduction
Benzothiazole derivatives have attracted attention over a long period of time [2,3] due
in the main to their wide spectrum of biological activities, which include uses as antitubercular
4], antibacterial [5], anti-inflamatory [6], anticonvulsant [7], antimalarial [8], anthelmintic [9],
[
antileishmanial [10], antidiabetic [11], antidepressant [12] and antitumor agents [13]. The
benzothiazole framework remains today as an important scaffold for the design and synthesis of
active molecules [14,15].
Our interest in the biological and structural chemistry of heteroaromatic compounds,
especially hydrazonyl derivatives [16-23] has resulted in us continuing our studies of
benzothiazole derivatives, 1, prepared as shown in Scheme 1, from 2-hydrazinylbenzothiazole,
2
. Previously, some of us had reported the structures of several hydrazonal derivatives [24,25],
which had been used in in-vitro studies against three neoplastic cancer cells [26,27]. A more
recent report on the anti-tumour and structural chemistry of such compounds by a Polish group
[
28] indicated strong antiproliferative effects on tumor cells and cytotoxic effects on
fibroblasts.
We now wish to report the results of an antimycobacterial activity study against M.
tuberculosis ATTC 27294 of eight derivatives, 1a-1i, see Scheme 1. We also report the crystal
structures of the 4-MeOC H derivative, 1e, the pyridin-2-yl derivative, 1h, and two 2-
6
4
hydroxylphenyl derivatives, 1f and 1i. Each of the last three compounds is able to act as a
tridentate ligand, while in addition, compounds, 1f and 1i, were chosen for further study of the
tautomeric amino-imino equilibrium, see Scheme 2. Previous reports had shown that the only
known compounds, 1, having imino forms in the solid state were the 2-hydroxyphenyl
derivatives, 1d and 1j, see Scheme 2. However our new results indicate that 2-hydroxyphenyl
derivatives can also exist in the imino form in the solid state.
We also report the crystal structure and the antimycobacterial activity of a Cu(II)
complex, 3, formed from Cu(II)(OSO CF ) and 1d, see Scheme 3. Metal complexes of
2
3 2
benzothiazolyl hydrazone derivatives have occasionally been reported, e.g., complexes of Cu(II)
29-31], Ni(II) [32] amd molybdenum [33]. A Romanian group [29-31] characterized solid
[
copper complexes of benzothiazolyl hydrazone derivatives using IR, UV and EPR spectroscopic
data, elemental analysis and molar conductivity, and reported anti-fungicide and anti-bactericide
2

ACCEPTED MANUSCRIPT
properties: among the complexes isolated were [Cu(HL)X(H
2
O)], where H L = 1d, and X = Cl
2
or Br. However no crystal structure determinations of the metal complexes have been made.
2
. Results and discussion
.1.Synthesis and characterization
2
Reactions between 2-hydrazinylbenzothiazole, 2, and substituted benzaldehydes in refluxing
methanol produced the 2-arylidenehydrazinobenzothiazole derivatives, 1, in yields between 55-
7
5% after recrystallization from MeOH. The choice of the benzaldehydes used in this study
was based on our earlier results of the anti-TB activities of heteroaromatic hydrazones [34-39]
as well as those for the benzaldehyde precursors [40], see Table 1. All the hydrazones were
characterized from NMR and IR spectra, and by accurate mass measurements, and additionally
for compounds 1e, 1f,1h and 1i by X-ray crystallography.
2.2.Biological results
The results of the antimycobacterial activity of compounds 1 are shown in Table 1. The most
active compounds, 1c-1e and 1h, have superior activities to that of the standard drug,
ethambutol. As these active compounds contain both electron releasing and withdrawing
substituents, there is no apparent role for electronic effects in the activities. However it is of
interest that two of these compounds, namely 1d [a potential ONN chelator] and 1h [a potential
NNN chelator] have the capacity to act as tridentate ligands. It has been argued that having a
chelator scaffold, especially one with a tridentate ability, is a necessity for a drug to be able to
overcome multidrug resistance [41, see also 36]. Another important is the hydrophilicity, with a
clogP value less than 5.0 being desirable. As shown in Table 1 some of the compounds studied
do have calculated values [42] less than 5, including active compounds,1c and 1h. All in all, the
active compounds can be considered as reasonable starting points for further study for
compounds having improved antitubercular activity.
2.3. Crystal structures of compounds 1.
Compounds, 1e, 1h, 1f and 1i, crystallize in monoclinic phases: compound, 1i in the P2 /n space
1
group with Z = 4, compounds 1e and 1f in the P2 /c space group with Z = 4 and compound 1h
1
in the I2/a space group with Z = 8. The asymmetric unit in each case is a single molecule.
Compounds, 1e, 1h and 1i were isolated in the amino form, while compound 1f was found in
the imino form. Despite the different tautomeric forms of 1e (the 4-MeO-phenyl derivative) and
1
f (the 2-HO-4-MeOC H derivative), the two compounds have similar cell dimensions and
6 3
furthermore their intermolecular interactions combine to form similar sub-structures, see later.
A small percentage (8.5 %) of disorder (flip disorder) involving the exchange of the
positions of the nitrogen and sulfur atoms in the thiazole ring was found for compound 1e, with
o
the two conformations differing by a rotation of 180 about the C2—N1 bond. Such flip
3

ACCEPTED MANUSCRIPT
disorder has been previously recognized for other thiazolyl derivatives [43]. The atoms were
labelled S1A and N3A in the major conformation and as S1B and N3B in the minor
conformation. The atom arrangement and numbering scheme for the major conformer of 1e is
illustrated in Fig. 1, along with those of compounds, 1f, 1h and 1i. Due to the small percentages
of the minor forms, and their practically negligible involvement in the intermolecular
interactions, the minor conformations were ignored in the discussion of intermolecular effects.
The crystal structure of a sample of compound 1d, recovered from a failed attempt to
complex MeSnCl in methanol solution, was also attempted. The structure determination, from
3
data collected at 100K, indicated a little flip disorder of 3.2%. However the same monoclinic
phase was determined with very similar cell dimensions as previously reported for 1d, without
flip disorder, by Katava et al [28] using data collected at 296 K for a sample recrystallised from
DMSO solution: cell dimensions at 100K: a, b and c = 15.3562(10), 4.5316(2) and 17.6862(12)
o
Å, β = 91.924(6) ; at 296 K: a, b and c = 15.6365(10), 4.5903(3) and 17.6379(13) Å, β =
o ,
9
1.813(6) As the important intra- and intermolecular interactions are the same in both cases for
this imino derivative, no further discussion of the structure of our sample will be made.
The benzothiazole ring is essentially planar in all cases and makes angles with the
o
phenyl ring of 8.70(8) in 1e, 6.03(5) in 1f, 13.30(6) in 1h and 2.17(9) in 1i, as well as 3.7(2) in
1
d. Of interest the smallest of these angles are for the 2-hydroxyphenyl derivatives, in which the
hydroxyl group is involved in intramolecular hydrogen bonding.
.4.Imino and amino tautomers
2
The only imino conformers previously reported, namely 1d [28] and the DMSO solvate of 1g
24], were both 2-hydroxyphenyl derivatives, see Scheme 2. However as found in this study,
[
some 2-hydroxyphenyl derivatives can be isolated in the imino form. While the 2-hydroxy-4-
methoxyphenyl derivative, 1f, was isolated in the imino form, the 2-hydroxy-5-methylphenyl
derivative, 1i, was determined to have the amino form. The amino form is by far the more
frequently determined tautomeric form for 1, see Supplementary Table 1: the structure
determinations of 1f and 1h further increased the number of known amino forms.
Bond angles and lengths in the linkers between the benzothiazole ring and the aryl ring
(
phenyl or heteroaryl) for imino and amino tautomers show considerable electron delocalisation,
when compared to standard single and double bond lengths, as shown in Supplementary Table
. Geometric parameters which differ the most significantly for amino and imino forms are the
1
N1-C2 and C2-N3 bond lengths and the C4-N3-C2 and C2-N1-N2 bond angles, see
Supplementary Table 1.
2.5.Intermolecular interactions of the amido tautomers.
The intermolecular interactions in compounds, 1e, 1h and 1i, are listed in Table 2.
4

ACCEPTED MANUSCRIPT
A general finding for non-solvated amido tautomers is the formation of inversion dimers
generated from pairs of N1—H1···N3 hydrogen bonds, the strongest intermolecular interaction
present for these molecules. These dimers are found for all non-solvated amido tautomers
formed from phenyl [24,25,28], naphthalenyl [28] and such heteroaromatic compounds as
pyridinyl, thienyl and pyrrolyl derivatives [25], but not from the furanyl derivative [25]. The
three amido tautomers, 1e,1h and 1i, reported here, form this major dimer, see Fig.1. Such
dimer formation has also been reported for the mono-hydrate of 3-MeO-4-HOC H but not that
6
3
of the 4-HOC H derivative.
6
4
There are subtle conformational differences between the dimers of 1e, 1h and 1i, which
stem from the orientation of the monomers within the dimer, as illustrated in Fig.2. In the dimer
of 1e, the non-hydrogen atoms are essentially coplanar, each molecule of 1h provides a concave
surface towards the other monomer, and in the dimer of 1i, the two molecules, each essentially
planar, are not coplanar, there being a perpendicular distance between the best planes through
the molecules of 1.00(2) Å.
Other generally found intermolecular interactions in these amido derivatives are weak
π···π interactions, see Table 3. In the subsequent discussion, the aromatic rings are designated
benzo, thiazolyl and phenyl for the rings containing atoms, C5, C2 and C12, respectively. In
compound 1e, the weak π···π interactions generate dimers as shown in Fig. 3a. Such dimers
combine with the N1—H1···N3 linked dimers in two ways to form more complex sub-
structures, as illustrated in Figs. 3b-d. In Figs. 3b and 3c, the two distinct π···π and N1—
H1···N3 dimers are linked by C8—H8···π(benzo ring) interactions into chains: the angle
between the best planes through the molecules in the π···π interaction and that of the N—H···N
o
dimers is 75.0 , see Fig. 3c. Fig. 3d illustrates the linking of the N1—H1···N3 dimers by the
π···π interactions, while Fig. 3e shows the overlap of the π systems in successive rows of this
substructure. As can be seen, the π overlap involves essentially the thiazolyl units and the linker
chains of a molecule of each dimer in successive layers. The perpendicular distance between the
i
parallel thiazolyl units is 3.343 Å. There are some short contacts, e.g. C6—H6···O2 , C17—
ii
iii
H17C···N2 and C10—H10···π(benzo) , which further reinforce the structure: symmetry
operations: i = 1+x,12-y, ½+x; ii = -x,1-y,-z; iii = 1-x,2-y,z.
Compound 1h has a similar structure, in that weak π···π dimers are also formed, which
combine with the N1—H1···N3 dimers to give similar sub-structures to those found in
compound 1e. Due to the similarity of the arrangements, no figures are shown specifically for
compound 1h. However, some slight differences can be mentioned, for example the π···π
dimers in 1h are made up from pairs of π(pyridinyl)··· π(benzothiazolyl) interactions, rather
than a single π(thiazolyl)···π(thiazolyl) interaction as in compound 1e, and that the π···π
dimers and N—H···N dimers in 1h are linked by two C—H···π iteractions, namely C13—
5

ACCEPTED MANUSCRIPT
H13···Cg3 and C14—H14···Cg1 interactions, rather than by just one as in 1e. A short contact
i
exists between C6—H6···π(benzo) : symmetry code: i = 1-x,1/2+y, ½-z.
The situation is somewhat different in 1i, in which the 2-hydroxyl group is strongly
involved in intramolecular interactions. Stacks of molecules are generated by linking the N1-
NH1---N3 dimers, shown in Fig. 2c, by π(benzo)···π(thiazole) and C17—H27B···π interactions,
see Fig. 4. The C17—H17B···π interaction, involving the phenyl ring, is more π (allyll) like
than a π(phenyl) interaction, with the closest links to C11, C14 and C15 ring atoms. Fig. 4c
shows the overlap of the dimers in successive layers in the the 2-molecule wide column.
Somewhat differently to the situations in compounds, 1e and 1h, the π overlap in 1i involves
both molecules in each layer with those in adjacent layers, and there is overlap between the aryl
rings as well as between the aryl ring and the delocalised linker chain, compare Figs. 3e and
4
c. These features plus the short perpendicular distance between successive layers of 3.205 Å,
clearly suggests that this is a strong interaction.
A short contact C6—H6···π contact is indicated in the lis file, which if significant
would result in the columns being linked into, at best, a very weakly held sheet of molecules.
2.6.The imino derivative, compound 1f
As with all the 2-hydroxy derivatives so far studied, the 2-hydroxy group in the imino
compound, 1f is involved in an intramolecular hydrogen bond, see Fig. 1. The N—H···N dimers
in 1f are N3—HN3···N1 linked dimers, see Fig. 2d. Despite the fact that 1f is an imino
derivative, with the hydrogen on the thiazolyl nitrogen, N3, and 1e is an amino tautomer, with
the hydrogen on N1 of the hydrazonyl group, similar sub-structures are formed in both
compounds from combination of different N—NH···N, π···π and C—H···π interactions, for
example, compare Fig.3 for 1e with Fig. 5 for 1f. Thus in 1f, N3—HN3···N1 linked dimers in
combination with π(thiazolyl)···π(thiazolyl) linked dimers and C8—H8···π(benzo) interactions,
generate the sub-structure shown in Fig. 5b and c. In 1e, the combination of interactions are
N1—NH1···N3 linked dimers, π(thiazolyl)···π(thiazolyl) linked dimers and C8-H8···π(phenyl)
interactions. Direct linkage of the N3—NH3···N1 dimers by (thiazolyl)···π(thiazolyl)
interactions generates two-molecule wide columns as illustrated in Fig. 5d. The overlap of the
·
π systems in the arrangement is illustrated in Fig. 5e, with a perpendicular distance of 3.212 Å
between the best planes of the dimers, which indicates a strong interaction. Combination of all
the intermolecular interactions creates a three dimensional structure. Additional short contacts,
i
ii
iii
C17—H17C---N and C6—H6···O2 hydrogen bonds and a C17—H17A···π interaction, are
indicated in the lis-file, which could augment the stability of the three dimensional structure.
[
symmetry codes: i = 1-x,1-y,1-z; ii = 1+x,1/2-y, ½+z; iii = x, 1+y,z]. The C17—H17A··π
interaction is best described as a π(allyl) rather than a π(phenyl) interaction.
Only two non-solvated imino tautomers, 1d [28] and 1i [this study], have been
characterised by X-ray crystallography, and each has a different set of classical hydrogen
6

ACCEPTED MANUSCRIPT
bonds. In contrast to the situation in 1f detailed above, in 1d no N—HN···N dimers are
produced, instead the strong classical hydrogen bonds, N—H···N, produce spiral chains [28].
2.7.Structure of the copper complex, 3.
The sample of 3 used in the structure determination was recrystallised from moist
methanol solution, see Scheme 3. The blue complex crystallizes in the triclinic phase group, P-
, with Z = 2. The asymmetric unit is a single molecule. The atom numbering system and atom
1
arrangements of the single molecule are shown in Fig. 6a. The monomer has a square pyramidal
geometry with a 5-coordinate copper(II) ion, a water ligand, a trifluromethylsulfonate anion and
an essentially planar O,N,N- mono-deprotonated 1d anion, see Table 3 for selected bond angles
and lengths. There are two intramolecular interactions, namely a C5—H5···O1 hydrogen bond
and a C17—F2···π(ring containing Cu1 and O2) interaction. The tridentate ligand and the water
molecule provide the donor atoms in the basal plane of the 5-coordinate monomer, while the
trifluoromethylsulfonate ligand occupies the apical site. The Cu(II) ion sits ca 0.2 Å above the
basal plane. Each pair of trans sites in the basal plan is ocupied by O and N donors with
o.
∠
O(water)-Cu-N2 = 178.48(7) and ∠O(deprotonated hydroxyl)-Cu-N3 = 171.31(8)
Monomers are linked into centrosymmetric dimers by Cu···π [44-46] and by π···π
interactions utilising the π system of the deprotonated O,N,N-ligand. Each of the two Cu(II)
centres in the dimer makes short Cu···π interactions with specific rings, namely the delocalised
rings with atoms [Cu1,O2,C12-C10,N2] and atoms C11-C16: the two Cu(II)···Cg distances of
3
.766 and 3.819 Å, respectively. Considering that the π system of two fused delocalised rings
involves both rings, it seems that the midpoint of the C4-C9 bond, common to the two rings, is
i
i
i
an appropiate centroid, Cg , for the π system of both rings. Such a Cg provides a Cu···Cg
distance of 3.571 Å, see Fig. 6b. Including this interaction leads to two octahedral Cu(II)
i
i
centres in the dimer, with the sixth sites, apical sites, occupied by Cg , and an
∠ O3-Cu---Cg =
o
1
62.4 . Table 3 lists the bond angles and lengths involving this sixth ligand. The Cu—Cu
separation in the dimer is 4.823(2) Å.
The overlap of the π systems in the π···π interactions involving the deprotonated 1d
ligand in the dimer is extensive, see Fig. 6c and Table 4, and with the relatively short
perpendicular distance between the parallel benzothiazolyl moieties of 3.3409(9) Å, these are
good indications of strong interactions.
The dimers are building blocks for more elaborate supramolecular arrangements.
Firstly, the dimers form two-molecule wide columns on interacting with a set of O1—H1···O5,
O1—H2···O2 and N1—Hn1···O4 hydrogen bonds, see Fig. 7a. These columns are further
linked by C10—H10···O5 and C7—H7···F3 hydrogen bonds into a three dimensional array:
this has not been illustrated. Secondly, the dimers are linked by π(benzo)···π(benzo)
interactions to form a tilted column of molecules, as shown in Fig 7b. The overlap of the π
7

ACCEPTED MANUSCRIPT
systems in the π(benzo)···π(benzo) interactions is illustrated in Fig.7c. The extesive overlap of
the π systems and the perpendicular distance between the parallel ligands in the
π(benzo)···π(benzo) interaction of 3.4669(10) Å, indicates this is a strong interaction.
To form the complex, the ligand, 1d, undergoes both a deprotonation of the hydroxyl
group and tautomerisation from the imino form to the amino form. However there are only
small differences between corresponding bond lengths and angles in the complex and ligand,
1
d, see Table 3. The most significant differences involve a shortening of the C2-N3 and a
lengthening of the N1-C2 bonds on complexation.
Complex 3 was found to be active againnst the Mycobacterium tuberculosis H37Rv
strain but less so than than the ligand, 1d, based on the MIC(ꢀM,) values of 4.9 to 12.4 for the
ligand and its complex. An interpretation of the reduced potency of the complex is that strong
complexation by copper results in less of the active ligand being freely available for activity
against M. tuberculosis ATTC 27294. If correct, it does provide evidence that good ligand
abilities of the drugs are important.
2.8.Comparison of compounds 3 and 4.
Calinescu et al [29-31] reported spectral and other data for a few solid copper(II)
complexes of benzaldehyde benzothiazolyl hydrazone ligands, 1. Among the complexes
indicated from the IR, UV and EPR data and elemental analysis was grey-green [aqua{2-(2-
benzothiazolyhydrazonyl)phenoxyl})chlorocopper(II)].monohydrate, [4.(H O)], see Scheme 3,
2
formed from reaction between Cu(II)Cl and 1d in refluxing ethanol [30]. Their suggested
2
structure for pentacoordinate square pyramidal 4 agrees very well with the X-ray structure of
monomeric 3, found in this study, with the chloro ligand in 4 replacing the sulfonate ligand in
3
. The IR spectrum of 3 was similar to that of 4, except for the additional bands due to the
different anions.
The complex, 4, was reported to be only moderately active against Gram positive and
HGram negative bacteria and fungi.
Conclusion
Prior to this work, 2-hydroxyphenylideneydrazinylbenzothiazole derivatives had only been
isolated in the imino tautomer form. However this study has revealed that this is not always the
case as shown by 1f (aryl -= 2-HO-5-MeC H ), which was isolated in the amino form. While the
6
3
amino form is the most frequently isolated, further study is required to establish the the most
important in deciding whether imino or amino forms are isolated. Four compounds, namely 1c
(
aryl = 2-O NC H ), 1d, (aryl = 2-HOC H ), 1e and 1h, were found to have superior ant-TB
2 6 4 6 4
activities against M. tuberculosis ATTC 27294 compared to that of the standard drug,
ethambutol in in-vitro studies. It is of interest that two of these compounds have the capacity to
8

ACCEPTED MANUSCRIPT
act as tridentate ligands, namely 1d [a potential ONN chelator] and 1h [a potential NNN
chelator]. Conformation of the chelating ability of 1d, HL, towards copper (II) was the
isolation of the dimeric octahedral complex{[(L)(H O)Cu][O SCF ]} , 3, from interaction with
2
3
3
2
(II)
Cu (O SCF ) in moist MeOH. The monomeric square-pyramidal [(L)(H O)Cu][ O SCF ],
3
3 2
2
3
3
with an axial OS(O )CF ligand and equatorial H O ligand, dimerises via extensive π---π
2
3
2
interactions involving the complete planar L-Cu fragments.
3
. Experimental
.1. General
3
Melting points were determined using an MQAPF-302 (MicroQuímica Ltd, Santa Catarina,
Brazil) apparatus and are uncorrected. NMR spectra were analysed using a 400 or 500 MHz
Bruker AC spectrometer. Infrared spectra were obtained using a Thermo Nicolet 6700
spectrometer or as neat powders using a Perkin Elmer UART two instrument, with ATR
Diamond Cell. High-resolution mass spectra were acquired on a Bruker compact-Tof and on a
Water Mass Spec. Model Xevo G2 QT of instrument and MassLynx version 4.1 software. The
progress of reactions was monitored by thin-layer chromatography (TLC) using ultraviolet light
detection. For column chromatography, Merck silica gel (70-230 or 230-400 mesh) was used.
Solvents and reagents were used without further purification.
3
.2. General procedure for the synthesis of 2-arylidenehydrazinobenzothiazole
compounds.
The desired compounds 1 were prepared by reaction between 2-hydrazinobenzothiazole 1 (0.16
g, 1 mmol) and the appropriate arenecarbaldehyde (1.0 eq., 1 mmol) in methanol (15 mL). The
reaction mixture was stirred for 30-60 minutes at reflux, concentrated under reduced pressure,
washed with cold ethanol (2.0 mL), and finally recrystallised from methanol..
(
E)-2-(2-Benzylidenehydrazinyl)benzo[d]thiazole, 1a, using benzaldehyde
o
-1
M .p. 218-220 C. IR (cm , KBr) ν 3070 (C-H, Ar-H), 1627 (C=N, cyclic), 1576 (C=N,
max
1
open). H-NMR (500MHz, DMSO-d ) δ (ppm): 12.29 (1H, s, NH); 8.14 (1H, s, N=CH); 7.77
6
(
1H, d, J= 7.5, H4); 7.70 (2H, d, J= 7.1, H1’ and H5’); 7.44 (1H, d, J= 7.5, H7); 7.42 (3H, m,
H2’, H3’ and H4’); 7.30 (1H, t, J= 7.5, H5 or H6); 7.11 (1H, t, J= 7.5, H5 or H6) ppm.
1
3
C-NMR (125 MHz, DMSO-d ) δ(ppm): 167.0; 142.0; 134.2; 132.7; 129.4; 129.1; 128.7;
6
1
28.7; 128.4; 126.4; 125.8; 121.5; 121.4; 118.0 ppm
+
+
HR-MS (ESI): Calcd for C H N S (M + H ): 254.0746; Found: 254.0741
14
12
3
9

ACCEPTED MANUSCRIPT
(
E)-2-(2-(2-Chlorobenzylidene)hydrazinyl)benzo[d]thiazole, 1b, from 2-
chlorobenzaldehyde
o
-1
Mp: 236-238 C. IR (cm , KBr) ν 3067 (C-H, Ar-H), 1614 (C=N, cyclic), 1562
max
1
(
(
C=N, open), 748 (C-Cl). H-NMR (500MHz, DMSO-d ) δ (ppm): 8.48 (1H, s, N=CH); 7.96
6
1H, dd, J= 7.5 and J= 2.5, H5’); 7.79 (1H, d, J= 7.5, H4); 7.53 (1H, dd, J= 6.9 and J= 2.2, H2’);
7
.43 (3H, m, H3’, H4’ and H7); 7.31 (1H, t, J= 7.5, H5 or H6); 7.13 (1H, t, J= 7.5, H5 or H6)
13
ppm. C-NMR (125 MHz, DMSO-d ) δ(ppm): 167.1; 132.4; 131.5; 130.9; 130.9; 130.0; 130.0;
6
+
1
27.6; 127.6; 126.4; 126.0; 121.9; 121.9; 121.6 ppm. HR-MS (ESI): Calcd for C H ClN S
14 11 3
+
(
M + H ): 288.0357; Found: 288.0355
(
E)-2-(2-(2-Nitrobenzylidene)hydrazinyl)benzo[d]thiazole, 1c, from 2-nitrobenzaldehyde
o
-1
Mp: 225 C (dec). IR (cm , KBr) ν 3065 (C-H, Ar-H), 1622 (C=N, cyclic), 1575 (C=N,
max
1
open), 1515, 1334 (NO ). H-NMR (500MHz, DMSO-d ) δ (ppm): 8.51 (1H, s, N=CH); 8.06
2
6
(
(
2H, m, H2’ and H5’); 7.81 (2H, m, H4 and H4’); 7.63 (1H, dt, J= 8.1 and J= 0.8, H3’); 7.48
1
3
1H, m, H7); 7.32 (1H, t, J= 7.5, H5 or H6); 7.14 (1H, t, J= 7.5, H5 or H6) ppm. C-NMR (125
MHz, DMSO-d ) δ(ppm): 167.2; 147.6; 147.6; 133.4; 133.4; 129.9; 129.9; 128.4; 127.7; 126.0;
6
+
+
1
24.6; 121.9; 121.9; 121.6 ppm. HR-MS (ESI): Calcd for C H N O S (M + H ): 299.0597
14 11 4 2
Found: 299.0595.
(
E)-2-((2-(Benzo[d]thiazol-2-yl)hydrazono)methyl)phenol, 1d, from 2-
hydroxybenzaldehyde
o
o
-1
Darkens on heating, dec. at 250 C. (Lit.value 250 C [30]). IR (cm , KBr) ν 3041 (C-H, Ar-
max
1
H), 1603 (C=N, cyclic), 1575 (C=N, open), 1198 (C-O). H-NMR (400MHz, DMSO-d ) δ
6
(
ppm): 12.17 (1H, s, NH); 10.45 (1H, s, OH); 8.45 (1H, s, N=CH); 7.75 (1H, d, J= 7.7, H4);
.62 (1H, d, J= 7.3, H5’); 7.36 (1H, m, H7); 7.31 (1H, dd, J= 8.2 and J= 7.3, H3’); 7.26 (1H, m,
7
1
3
H5); 7.10 (1H, d, J= 8.0, H6); 6.93 (1H, d, J= 8.2, H2’); 6.91 (1H, t, J= 7.3, H4’) ppm. C-
NMR (125 MHz, DMSO-d ) δ(ppm): 166.4; 156.5; 130.8; 130.8; 127.4; 126.1; 121.7; 121.5;
6
+
+
1
21.5; 119.6; 119.4; 119.4; 116.1; 116.1 ppm. HR-MS (ESI): Calcd for C H N OS (M + H ):
1
4
12
3
2
70.0696; Found: 270.0685
(
E)-2-(2-(4-methoxybenzylidene)hydrazinyl)benzo[d]thiazole, 1e, using 4-
methoxybenzaldehyde.
o
-1
M.p. 186-188º C (lit. value 189 C [29]). IR (cm , KBr) ν 3070 (C-H, Ar-H), 1608 (C=N,
max
1
cyclic), 1575 (C=N, open), 1247 (C-O-CH ). H-NMR (400MHz, DMSO-d ) δ (ppm): 12.10
3
6
(
1H, s, NH or OH); 8.09 (1H, s, N=CH); 7.75 (1H, d, J= 7.7, H4); 7.64 (2H, d, J= 8.8, H1’ and
H5’); 7.42 (1H, d, J= 8.1, H7); 7.29 (1H, dd, J= 8.1 and J= 7.3, H6); 7.09 (1H, dd, J= 7.7 and J=
1
3
7
.3, H5), 7.01 (1H, d, J= 8.8, H2’and H4’); 3.81 (3H, s, CH ) ppm. C-NMR (100 MHz,
3
DMSO-d ) δ(ppm): 166.8; 160.4; 160.4; 144.0; 129.0; 128.0; 128.0; 126.8; 125.8; 121.4; 121.3;
6
1
0

ACCEPTED MANUSCRIPT
+
+
1
18.0; 114.3; 114.3; 55.2 ppm. HR-MS (ESI): Calcd for C H N OS (M + H ): 284.0852;
15 14 3
Found: 284.0854.
(
E)-2-((2-(Benzo[d]thiazol-2-yl)hydrazono)methyl)-5-methoxyphenol, 1f, from 2-hydroxy-
4
-methoxybenzaldhyde
o
-1
M.p. 218-220 C. IR (cm , KBr) ν 3065 (C-H, Ar-H), 1613 (C=N, cyclic), 1576 (C=N, open),
max
1
1
1
230 (C-O-CH ), 1195 (C-OH). H-NMR (400MHz, DMSO-d ) δ (ppm): 12.01 (1H, s, NH);
3
6
0.74 (1H, s, OH); 8.38 (1H, s, N=CH); 7.71 (1H, d, J= 7.7, H4); 7.50 (1H, d, J= 8.6, H5’); 7.28
(
2H, m, H5 and H7); 7.07 (1H, t, J= 8.1, H6); 6.53 (1H, dd, J= 8.6 and J=2.4, H4’), 6.49 (1H, d,
1
3
J= 2.4, H2’); 3.78 (3H, s, CH ) ppm. C-NMR (100 MHz, DMSO-d ) δ(ppm): 165.7; 161.6;
3
6
1
61.6; 158.4; 129.6; 126.1; 121.8; 121.3; 121.3; 112.6; 106.4; 106.4; 100.9; 100.9; 55.2 ppm.
+
+
HR-MS (ESI): Calcd for C H N O S (M + H ): 300.0801; Found: 300.0805.
15
14
3
2
(
E)-2-(2-(2-Methoxy-4-nitrobenzylidene)hydrazinyl)benzo[d]thiazole, 1g, from 2-methoxy-
-nitrobenzaldehyde
4
0
-1
M.p. 238-240(dec.) C. 238-240 IR (cm , KBr) ν 3068 (C-H, Ar-H), 1616 (C=N, cyclic),
max
1
1
570 (C=N, open), 1510, 1326 (NO ), 1252 (C-O-CH ). H-NMR (500MHz, DMSO-d ) δ
2
3
6
(
ppm): 12.63 (1H, s, NH); 8.41 (1H, s, N=CH); 8.02 (1H, d, J= 8.5, H5’); 7.92 (1H, dd, J= 8.5
and J= 1.8, H4’); 7.86 (1H, d, J= 1.8, H2’); 7.80 (1H, d, J= 7.6, H4); 7.49 (1H, m, H7); 7.32
1H, t, J= 7.6, H5 or H6); 7.14 (1H, t, J= 7.6, H5 or H6); 4.00 (3H, s, CH ) ppm.
(
3
1
3
C-NMR (125 MHz, DMSO-d ) δ(ppm): 156.9; 156.9; 148.3; 148.3; 128.9; 126.0; 125.4;
6
1
25.4; 121.9; 121.9; 121.5; 116.0; 116.0; 106.8; 56.4 ppm. HR-MS (ESI): Calcd for
+
+
C H N O S (M + H ): 329.0703; Found: 329.0691
15
13
4
3
(
E)-2-(2-(Pyridin-2-ylmethydene)hydrazinyl)benzo[d]thiazole, 1h, from pyridin-2-
ylcarbaldehyde
0
-1
MP: 217-219 C. IR (cm , KBr) ν 3072 (C-H, Ar-H), 1621 (C=N, cyclic), 1575 (C=N, open).
max
1
H-NMR (500MHz, DMSO-d ) δ (ppm): 12.57 (1H, s, NH); 8.60 (1H, d, J= 4.7, H2’); 8.14 (1H,
6
s, N=CH); 7.88 (2H, m, H4’ and H5’); 7.81 (1H, m, H4); 7.50 (1H, m, H7); 7.39 (1H, ddd, J=
6
.6, J=4.7 and J= 1.3, H3’); 7.32 (1H, t, J= 7.5, H5 or H6); 7.14 (1H, t, J= 7.5, H5 or H6) ppm.
1
3
C-NMR (125 MHz, DMSO-d ) δ(ppm): 168.0; 153.0; 149.4; 149.4; 142.0; 136.7; 136.7;
6
+
+
1
2
25.9; 123.8; 123.8; 121.8; 121.5; 119.3 ppm. HR-MS (ESI): Calcd for C H N S (M + H ):
13 11 4
55.0699; Found: 255.0689
(
E)-2-((2-(Benzo[d]thiazol-2-yl)hydrazono)methyl)-4-methoxyphenol, 1i], from 2-hydroxy-
-methybenzaldhyde
5
1
1

ACCEPTED MANUSCRIPT
0
-1
MP: 224-226 C(dec). IR (cm , KBr) ν 3072 (C-H, Ar-H), 1626 (C=N, cyclic), 1572 (C=N,
max
1
open). H-NMR (500MHz, DMSO-d ) δ (ppm): 12.29 (1H, s, NH); 8.14 (1H, s, N=CH); 7.77
6
(
1H, d, J= 7.5, H4); 7.62(1H, d, J = 7.6, ), 7.44 (1H, d, J= 7.5, H7); 7.37(1H,d); 7.31 (1H, t, J=
7
.5, H5 or H6); 7.11 (1H, t, J= 7.5, H5 or H6) , 7.03(1H,s) ppm.
+
HR-MS (ESI): Calcd for C H N O S (M + H ): 284.0852; Found: 284.0853.
15
14
3
3
.3.Preparation of aqua(trifluoromethylsulfonato-O)(2-hydroxybenzaldehyde 2-
benzothiazolyl hydrazone-N,N,O)copper(II)
A solution containing 2-hydroxybenzaldehyde-2-benzothiazolyl hydrazone (1mmol, 0.270g)
II
and Cu (O SCF ) (1mmol,0.362g) in MeOH (20ml) was refluxed for 30 min. The solution was
3
3 2
filtered hot and left at room temperature. The deep blue crystals which formed after 2 days were
collected, and dried in air, and recrystallized from MeOH..
Anal: Calc for 3 (C H CuF N O S ) (3),: C, 36.10; H: 2.42; N: 8.42%; Found: C, 36.21; H:
1
5
12
3
3
5 2
2
.29; N: 8.34%;
IR 3445 (br), 3140, 1610(C=N), 1559, 1364(SO),13 02, 1150(S)
3
.4.Anti-mycobacterial activity
The anti-mycobacterial activities of compounds, 1, were assessed against M.
tuberculosis ATTC 27294 using the micro plate Alamar Blue assay (MABA) [47]. This
methodology is nontoxic, uses a thermally-stable reagent and shows good correlation with
proportional and BACTEC radiometric methods [48,49]. Sterile deionized water (200 ml) was
added to all outer-perimeter wells of 96 sterile well plates (Falcon, 3072: Becton Dickinson,
Lincoln Park, NJ) to minimize evaporation of the medium in the test wells during incubation.
The 96 plates received 100 mL of the Middlebrook 7H9 broth (100 mL) (Difco laboratories,
Detroit, MI, USA) and successive dilutions of the compounds were made directly on the plate.
The final drug concentrations tested were 0.01-20.0 mg/mL. Plates were covered and sealed
0
with parafilm and incubated at 37 C for five days. To the plates were added a freshly prepared
1
:1 mixture of Alamar Blue (25 ml) (Accumed International, WestlakeOhio) reagent and 10%
tween 80, followed by incubation for 24 h. A blue color in the well was interpreted as no
bacterial growth, and a pink color was scored as growth. The minimal inhibition concentration
(
MIC) was defined as the lowest drug concentration, which prevented a color change from blue
to pink. Results are listed in Table 1.
3
.5. X-ray crystallography.
Data for compounds 1d, 1e and 1f, at 100 K, were obtained with Mo radiation and for 1i and 3,
at 293 K, with Cu radiation. by means of a Rigaku Saturn724+ (2x2 bin mode) of the NSC
1
2

ACCEPTED MANUSCRIPT
crystallographic service, based at the University of Southampton. Data collection, data reduction
and unit cell refinement were achieved with CrystalClear-SM Expert 3.1 b27 [50] for 1d, 1e, 1f,
and 1i, and for 3 by CrysAlisPro 1.171.38.43 [51]. The thiazolyl moiety in compounds 1d and
1
e were refined with a disorder model corresponding to a ring flip, which exchanges the S and
N orientation, using PART n commands An empirical absorption correction program, part of the
Rigaku packages were used. The program MERCURY [52] was used in the preparation of the
Figures. SHELXL97 [53] and PLATON [54] were used in the calculation of molecular
geometry. The structures were solved by direct methods using SHELXS-97 [55] and fully
refined by means of the program SHELXL-97 [53].
Difference map peaks provided positions for hydrogens attached to nitrogen and oxygen
atoms. The coordinates, along with isotropic displacement parameters, were fully refined. All
other hydrogen atoms were placed in calculated positions. Crystal data and structure refinement
details are listed in Table 5.
Supplementary material
Supplementary Table 1, with information on conformations of 2H-chromene-3-carboxylate
derivatives and full details of the crystal structure determinations in cif format are available in
the online version,at doi: xxxxx. The cif-files have also been deposited with the Cambridge
Crystallographic Data Centre with deposition numbersxxxxxx for compounds xxx, respectively,
copies of which can be obtained free of charge on written application to CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK (fax: +44 1223 336033); on request by e-mail to
deposit@ccdc.cam.ac.uk or by access to http://www.ccdc.cam.ac.uk.
Acknowledgements
The authors thank the National Crystallographic Service, University of Southampton, UK, for
the data collection, and for their help and advice. JLW thanks CNPq, Brazil for support.
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Pharm, 347 (2014) 432-448.
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J. Med. Chem. 117 (2016) 335-354.
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1
5

ACCEPTED MANUSCRIPT
Table 1 In-vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC
2
7294, susceptible to ethambutol).
b
Compound
MIC (µM)
Mutagenic/
Tumorigenic
clog P
a
1
1
1
1
1
1
1
1
3
a
b
c
d
e
f
>100
>100
10.5
11.6
8.8
167
>100
4.9
None/none
None/none
None/none
None/none
None/none
None/none
None/none
Low/none
5.6433
6.2493
4.5513
5.2976
5.5733
5.2276
4.4813
4.6964
g
h
12.4
15,3
0.46
Ethambutol
Isoniazide
a
Calculated using Data Warrior program (http://www.openmolecules.org/datawarrior.

ACCEPTED MANUSCRIPT
Table 2. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular
o
interactions (Å, )
__________________________________________________________________________________________________________________________
(
a) Intramolecular hydrogen bonds
D—H···A
D—H
H···A
D···A
D—H···A
1
i
O1—H1···N2
0.88(3)
1.88(3)
2.668(2)
149(3)
(
b) Intermolecular H bonds
D—H···A
D—H
0.94(2)
0.98
0.88(2)
0.82(4)
H···A
2.02(2)
2.62
2.11(2)
2.20(4)
D···A
D—H···A
174.2(16)
158
175
Symmetry code
1-x,2-y,-z
-x,1-y,-z
1-x,1-y,1-z
2-x,1-y,1-z
1
1
1
1
e
e
h
i
N1—Hn1···N3A
C17—H17C···N2
N1—H1···N3
N1—HN1···N3
2.955(4)
3.545(2)
2.9843(15)
3.013(3)
168(3)
(
c) Y—X···π
Y—X···Cg
C8—H8···Cg(benzo)
C13—H13···Cg(benzo)
C14—H14···Cg(thiazolyl)
C17—H17B···Cg(pyridnyl)
X···Cg
2.92
2.74
2.98
3.34
Xperp
2.71
2.68
2.86
2.71
γ
Y—X···Cg Y···Cg
1
1
1
1
e
h
h
i
22.06
135
141
119
143
3.655(2)
3.5279(17) 1/2-x,-1+
3.5374(17) 1/2-x,-1+
1-x,-1/2+
12.51
16.22
28.48
4.150(2)
1+x,y,z
a
(
d) π··π interactions
Cg(I)···Cg(J)
Cg···Cg
α
β
γ
CgIperp
CgJperp
1
1
1
1
1
e
h
h
i
Cg(thiazolyl···Cg(thiazolyl)
Cg(pyridinyl)···Cg(benzothiazolyl) 4.1602(8)
Cg(benzothiazolyl)···Cg(pyridinyl) 4.1602(8)
4.2103(16) 0.0(10)
37.4 37.4 3.3433(8)
30.6 28.4 3.6601(6)
28.4 30.6 3.5808(4)
27.6 26.7 3.4642(9)
3.3433(8)
3.5808(4)
3.6601(6)
3.4357(10) -1+
1+
1-x
1-x
1-x
13.30(6)
13.30(6)
3.8769(13) 0.97(11)
3.8769(13) 0.97(11)
Cg(thiazolyl)···Cg(benzo)
Cg(benzo)···Cg(thiazolyl)
i
26.7 27.6 3.4357(10) 3.4642(9)
= Angle Cg(I)-->Cg(J) ;
= Angle Cg(I)-->Cg(J) vector and normal to plane J (Deg) ; Cg-Cg = Distance between ring
Cg(I) = Plane number I ; α = Dihedral Angle between Planes I and J (Deg) ;
β
γ
Centroids (Å) ; CgI_Perp = Perpendicular distance of Cg(I) on ring J (Å); CgJ_Perp = Perpendicular
distance of Cg(J) on ring I (Å).

ACCEPTED MANUSCRIPT
Table 3. Selected geometric parameters for 3.
a) Parameters involving Cu in the complex, 3
(
Cu1-O1
Cu1-N2
1.9529(17)
1.9458(18)
Cu1-O2
Cu1-N3
1.9064(15)
1.9788(18)
Cu1-O3
Cu---Cg
2.3902(17)
3.571
i
O1-Cu1-O2
O1-Cu1-N3
O2-Cu1-N3
N2-Cu1-N3
89.20(7)
96.99(7)
171.31(8)
81.94(7)
O1-Cu1-O3
O2-Cu1-O3
O3-Cu1-N2
O3-Cu1···Cg 162.4
O2-Cu1···Cg
83.71(6)
102.87(6)
97.23(7)
O1-Cu1-N2
O2-Cu1-N2
O3-Cu1-N3
N3-Cu1···Cg
178.48(7)
91.75(7)
83.93(7)
79.0
i
i
i
i
i
N2-Cu1···Cg 87.3
93.8
O1-Cu1···Cg 102.4
(
b) Ring numbers, atoms and shapes in the complex 3
Ring
Atoms in ring
Ring shape
Ring 1
Cu1,N2,N1,C2,N3
Slight twist on Cu1-N2
Pucker parameters: Q(2) = 0.0754(17) Å, Phi(2) = 20.6(16)
o
Ring 2
Ring 3
Ring 4
Ring 5
Ring 6
S1,C2,N3,C4,C9
Cu1,O2,C12,C11,C10,N2 Essentially planar
C4-C9
C11-C16
Essentially planar
Essentially planar
Essentially planar
Essentially planar
S1,C2,N3,C4-C8
(
c) Comparison of selected parameters in the ligand, 1d, and complex, 3
Complex, 3
Ligand, 1d
Complex, 3
Ligand ,1d
N1-N2
N1-C2
C2-N3
C12-C11
S2-04
S2-O3
N2-N1-C2
C11-C10-N2
1.389(2)
1.351(3)
1.304(3)
1.419(3)
1.4427(17)
1.4386(18)
112.99(17)
123.3(2)
1.395(2)
1.299(2)
1.338(3)
1.410(3)
-
C10-N2
C12-O2
C11-C10
N3-C4
1.288(3)
1.329(3)
1.433(3)
1.404(3)
1.4510(16)
1.284(2)
1.352(2)
1.444(6)
1.414(3)
-
S2-O5
-
111.61(15)
122.47(17)
N1-C2-N3
N1-N2-C10
121.11(19)
118.10(18)
121.68(19)
114.91(15)

ACCEPTED MANUSCRIPT
Table 4. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular
o
interactions for 3 (Å, )
__________________________________________________________________________________________________________________________
(
d) Intramolecular hydrogen bonds
D—H···A
D—H
H···A
D···A
D—H···A
C5—H5···O1
0.93
2.42
3.154(3)
135
(
e) Intermolecular H bonds
D—H···A
O1—H1···O5
N1—Hn1···O4 0.81(3)
O1—H2···O2
C7—H7···F3
D—H
0.805(19)
H···A
1.88(2)
2.03(3)
1.93(2)
2.48
D···A
D—H···A
177(3)
171(3)
167(3)
168
Symmetry code
2-x,1-y,1-z
-1+x,y,z
2-x,1-y,1-z
1-x,-y,-z
2.679(2)
2.837(2)
2.696(2)
3.399(3)
3.141(3)
0.78(2)
0.93
C10—H10···O5 0.93
2.42
134
-1+x,y,z
a
(
f) Y—X···
π
interactions
a
Y—X···Cg
X···Cg
Xperp
γ
Y—X···Cg
20.77 125.28(12)
Cg3 is centroid of ring with atoms [Cu1,O2,C12,C11,C10,N2].
Y···Cg
4.312(2)
Symmetry code
C17—F2···Cg3 3.4020(16) 3.181
a
a
π
···π interactions
CgI···CgJ
Cg···Cg
α
β
γ
CgIperp
CgJperp
Symmetry code
Cg5···Cg1
Cg5···Cg2
Cg1···Cg3
Cg1···Cg5
Cg2···Cg5
Cg3···Cg1
Cg3···Cg3
Cg4···Cg4
Cg4···Cg6
3.5520(12)
3.7280(13)
3.9719(11)
3.5520(12)
3.7280(13)
3.9719(11)
3.4887(11)
3.8010(13)
3.8468(12)
3.8469(12)
2.68(10)
0.66(11)
3.67(8)
2.68(10)
0.66(11)
3.67(8)
0.00(8)
0.00(11)
0.20(9)
0.20(9)
17.4 17.3 3.3910(10) 3.3890(8)
26.3 25.9 3.3534(10) 3.3410(9)
1-x,1-y,1-z
1-x,1-y,1-z
1-x,1-y,1-z
27.8 31.3 3.3954(8)
17.3 17.4 3.3890(8)
25.9 26.3 3.3409(9)
31.3 27.8 3.5145(8)
3.5146(8)
3.3909(10) 1-x,1-y,1-z
3.3534(10) 1-x,1-y,1-z
3.3954(8)
3.4588(8)
1-x,1-y,1-z
1-x,1-y,1-z
7.5
7.5
3.4587(8)
24.2 24.2 3.4669(10) 3.4669(10) 1-x,-y,-z
25.8 25.7 3.4660(10) 3.4626(7) 1-x,-y,-z
25.7 25.8 3.4626(7) 3.4660(10) 1-x,-y,-z
Cg6···Cg4
a
Cg1 – Cg6 are centroids of rings with atoms [Cu1,N2,N1, C2, N3], [S1,C2,N3,C4,C9],
[
Cu1,O2,C12,C11,C10,N2], [ [C4-C9], C11-C16] and [S1,C2,N3,C4,C5,C6,C7,C8], respectively.
(
d) Cu···
π
interactions
CgI···Cu
Cg3···Cu1
Cg5···Cu1
d(CgI-Cu)
3.766
3.819
Cuperp
3.481
3.496
β
Symmetry code
1-x,1-y,1-z
1-x,1-y,1-z
2.41
23.72

ACCEPTED MANUSCRIPT
o
Table 2. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular interactions (Å, )
__________________________________________________________________________________________________________________________
(
a) Intramolecular hydrogen bonds
D—H···A
D—H
H···A
D···A
D—H···A
1
i
O1—H1···N2
0.88(3)
1.88(3)
2.668(2)
149(3)
(
b) Intermolecular H bonds
D—H···A
D—H
0.94(2)
0.98
0.88(2)
0.82(4)
H···A
2.02(2)
2.62
2.11(2)
2.20(4)
D···A
D—H···A
174.2(16)
158
175
168(3)
Symmetry code
1-x,2-y,-z
-x,1-y,-z
1-x,1-y,1-z
2-x,1-y,1-z
1
1
1
1
e
e
h
i
N1—Hn1···N3A
C17—H17C···N2
N1—H1···N3
N1—HN1···N3
2.955(4)
3.545(2)
2.9843(15)
3.013(3)
(
c) Y—X···π
Y—X···Cg
X···Cg
2.92
2.74
2.98
3.34
Xperp
2.71
2.68
2.86
2.71
γ
Y—X···Cg Y···Cg
1
1
1
1
e
h
h
i
C8—H8···Cg(benzo)
C13—H13···Cg(benzo)
C14—H14···Cg(thiazolyl)
C17—H17B···Cg(pyridnyl)
22.06
135
141
119
143
3.655(2)
3.5279(17) 1/2-x,-1+y,1-z
3.5374(17) 1/2-x,-1+y,1-z
1-x,-1/2+y,1/2-z
12.51
16.22
28.48
4.150(2)
1+x,y,z
a
(
d) π··π interactions
Cg(I)···Cg(J)
Cg···Cg
α
β
γ
CgIperp
CgJperp
1
1
1
1
1
e
h
h
i
Cg(thiazolyl···Cg(thiazolyl)
Cg(pyridinyl)···Cg(benzothiazolyl) 4.1602(8)
Cg(benzothiazolyl)···Cg(pyridinyl) 4.1602(8)
Cg(thiazolyl)···Cg(benzo)
Cg(benzo)···Cg(thiazolyl)
4.2103(16) 0.0(10)
37.4 37.4 3.3433(8)
30.6 28.4 3.6601(6)
28.4 30.6 3.5808(4)
27.6 26.7 3.4642(9)
3.3433(8)
3.5808(4)
3.6601(6)
1-x,1-y,-z
1-x,-y,1-z
1-x,-y,1-z
13.30(6)
13.30(6)
3.8769(13) 0.97(11)
3.8769(13) 0.97(11)
3.4357(10) -1+x,y,z
26.7 27.6 3.4357(10) 3.4642(9) 1+x,y,z
i
Cg(I) = Plane number I ; α = Dihedral Angle between Planes I and J (Deg) ; β = Angle Cg(I)-->Cg(J) ; γ = Angle Cg(I)-->Cg(J) vector and
normal to plane J (Deg) ; Cg-Cg = Distance between ring Centroids (Å) ; CgI_Perp = Perpendicular distance of Cg(I) on ring J (Å); CgJ_Perp =
Perpendicular distance of Cg(J) on ring I (Å).

ACCEPTED MANUSCRIPT
Table 3. Selected geometric parameters for 3.
a) Parameters involving Cu in the complex, 3
(
Cu1-O1
Cu1-N2
1.9529(17)
1.9458(18)
Cu1-O2
Cu1-N3
1.9064(15)
1.9788(18)
Cu1-O3
Cu---Cg
2.3902(17)
3.571
i
O1-Cu1-O2
O1-Cu1-N3
O2-Cu1-N3
N2-Cu1-N3
89.20(7)
96.99(7)
171.31(8)
81.94(7)
O1-Cu1-O3
O2-Cu1-O3
O3-Cu1-N2
O3-Cu1···Cg 162.4
O2-Cu1···Cg
83.71(6)
102.87(6)
97.23(7)
O1-Cu1-N2
O2-Cu1-N2
O3-Cu1-N3
N3-Cu1···Cg
178.48(7)
91.75(7)
83.93(7)
79.0
i
i
i
i
i
N2-Cu1···Cg 87.3
93.8
O1-Cu1···Cg 102.4
(
b) Ring numbers, atoms and shapes in the complex 3
Ring
Atoms in ring
Ring shape
Ring 1
Cu1,N2,N1,C2,N3
Slight twist on Cu1-N2
Pucker parameters: Q(2) = 0.0754(17) Å, Phi(2) = 20.6(16)
o
Ring 2
Ring 3
Ring 4
Ring 5
Ring 6
S1,C2,N3,C4,C9
Cu1,O2,C12,C11,C10,N2 Essentially planar
C4-C9
C11-C16
Essentially planar
Essentially planar
Essentially planar
Essentially planar
S1,C2,N3,C4-C8
(
c) Comparison of selected parameters in the ligand, 1d, and complex, 3
Complex, 3
Ligand, 1d
Complex, 3
Ligand ,1d
N1-N2
N1-C2
C2-N3
C12-C11
S2-04
S2-O3
N2-N1-C2
C11-C10-N2
1.389(2)
1.351(3)
1.304(3)
1.419(3)
1.4427(17)
1.4386(18)
112.99(17)
123.3(2)
1.395(2)
1.299(2)
1.338(3)
1.410(3)
-
C10-N2
C12-O2
C11-C10
N3-C4
1.288(3)
1.329(3)
1.433(3)
1.404(3)
1.4510(16)
1.284(2)
1.352(2)
1.444(6)
1.414(3)
-
S2-O5
-
111.61(15)
122.47(17)
N1-C2-N3
N1-N2-C10
121.11(19)
118.10(18)
121.68(19)
114.91(15)

ACCEPTED MANUSCRIPT
Table 4. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular
o
interactions for 3 (Å, )
__________________________________________________________________________________________________________________________
(
a) Intramolecular hydrogen bonds
D—H···A
D—H
H···A
D···A
D—H···A
C5—H5···O1
0.93
2.42
3.154(3)
135
(
b) Intermolecular H bonds
D—H···A
O1—H1···O5
N1—Hn1···O4 0.81(3)
O1—H2···O2
C7—H7···F3
D—H
0.805(19)
H···A
1.88(2)
2.03(3)
1.93(2)
2.48
D···A
D—H···A
177(3)
171(3)
167(3)
168
Symmetry code
2-x,1-y,1-z
-1+x,y,z
2-x,1-y,1-z
1-x,-y,-z
2.679(2)
2.837(2)
2.696(2)
3.399(3)
3.141(3)
0.78(2)
0.93
C10—H10···O5 0.93
2.42
134
-1+x,y,z
a
(
c) Y—X···
π
interactions
a
Y—X···Cg
X···Cg
Xperp
γ
Y—X···Cg
20.77 125.28(12)
Cg3 is centroid of ring with atoms [Cu1,O2,C12,C11,C10,N2].
Y···Cg
4.312(2)
Symmetry code
C17—F2···Cg3 3.4020(16) 3.181
a
a
π
···π interactions
CgI···CgJ
Cg···Cg
α
β
γ
CgIperp
CgJperp
Symmetry code
Cg5···Cg1
Cg5···Cg2
Cg1···Cg3
Cg1···Cg5
Cg2···Cg5
Cg3···Cg1
Cg3···Cg3
Cg4···Cg4
Cg4···Cg6
3.5520(12)
3.7280(13)
3.9719(11)
3.5520(12)
3.7280(13)
3.9719(11)
3.4887(11)
3.8010(13)
3.8468(12)
3.8469(12)
2.68(10)
0.66(11)
3.67(8)
2.68(10)
0.66(11)
3.67(8)
0.00(8)
0.00(11)
0.20(9)
0.20(9)
17.4 17.3 3.3910(10) 3.3890(8)
26.3 25.9 3.3534(10) 3.3410(9)
1-x,1-y,1-z
1-x,1-y,1-z
1-x,1-y,1-z
27.8 31.3 3.3954(8)
17.3 17.4 3.3890(8)
25.9 26.3 3.3409(9)
31.3 27.8 3.5145(8)
3.5146(8)
3.3909(10) 1-x,1-y,1-z
3.3534(10) 1-x,1-y,1-z
3.3954(8)
3.4588(8)
1-x,1-y,1-z
1-x,1-y,1-z
7.5
7.5
3.4587(8)
24.2 24.2 3.4669(10) 3.4669(10) 1-x,-y,-z
25.8 25.7 3.4660(10) 3.4626(7) 1-x,-y,-z
25.7 25.8 3.4626(7) 3.4660(10) 1-x,-y,-z
Cg6···Cg4
a
Cg1 – Cg6 are centroids of rings with atoms [Cu1,N2,N1, C2, N3], [S1,C2,N3,C4,C9],
[
Cu1,O2,C12,C11,C10,N2], [ [C4-C9], C11-C16] and [S1,C2,N3,C4,C5,C6,C7,C8], respectively.
(
d) Cu···
π
interactions
CgI···Cu
Cg3···Cu1
Cg5···Cu1
d(CgI-Cu)
3.766
3.819
Cuperp
3.481
3.496
β
Symmetry code
1-x,1-y,1-z
1-x,1-y,1-z
2.41
23.72

ACCEPTED MANUSCRIPT
Table 5. Crystal data and structure refinement
Identification code
Empirical formula
Formula weight
Temperature, K
Wavelength, Å
1d
1e
1f
1h
1i
3
C
C
14
H
11
N
3
OS
C
15
H
13
N
3
OS
C
15
H
13
N
3
O
2
S
C
13
H
10
N
4
S
C
15
H
13
N
3
O S
15 3 3 5 2
H12CuF N O S
269.32
100(2)
0.71073
283.34
100(2)
0.71075
299.34
100(2)
0.71075
254.31
100(2)
0.71075
283.34
293(2)K
1.54184
498.94
293(2)
0.71075
Crystal system, space group
Monoclinic,
P2(1)/n
Monoclinic,
P2(1)/c
Monoclinic,
P2(1)/c
Monoclinic, I2/a
Monoclinic,
P2(1)/n
Triclinic, P-1
Unit cell dimensions
a, Å
b, Å
c, Å
15.3562(10)
4.5316(2)
17.6862(12)
90
91.924(6)
90
1230.06(13)
4
1.454
12.9653(4)
5.0773(13)
20.6982(7)
90
97.2060(3)
90
1351.8(4)
4
1.392
12.5717(3)
5.1855(12)
20.7336(6)
90
94.8360(2)
90
1346.8(3)
4
1.476
5.7741(5)
5.84790(15)
25.7418(9)
90
99.685(3)
90
2340.72(13)
8
1.443
4.69760(10)
23.0158(7)
12.1108(3)
90
98.991(2)
90
1293.32(6)
4
1.455
8.0978(3)
10.5153(3)
12.1152(4)
102.402(3)
103.149(3)
109.762(3)
896.24(6)
2
o
α,
β,
γ,
o
o
3
Volume, Å
Z
Density (calculated) Mg/m
Absorption coefficient, mm
F(000)
3
1.849
1.517
502
-
1
0.257
560
0.238
592
0.248
624
0.262
1056
2.211
592
Crystal size, mm
0.180 x 0.015 x
0.560 x 0.070 x
0.060
0.156 x 0.069 x
0.011
0.101 x 0.096 x
0.091
0.080 x 0.010 x
0.005
0.100 x 0.080 x
0.060
0.010
Theta range for data
collection,
1.786 to 27.483
2.378 to 29.590
2.448 to 27.482
2.620 to 27.483
3.841 to 66.589
2.348 to 27.485
o
Index ranges
-19<=h<=19;
-17<=h<=17;
-7<=k<=5;
-28<=l<=26
12727
-15<=h<=16;
-6<=k<=6;
-26<=l<=26
21861
-20<=h<=18;
-7<=k<=7;
-32<=l<=33
7823
-5<=h<=4;
-26<=k<=26;
-14<=l<=14
10755
-10<=h<=10;
-13<=k<=13;
-15<=l<=15
14955
-5<=k<=5;
-22<=l<=22
Reflections collected
13611
Independent reflections
2782 [R(int) =
3483 [R(int) =
0.0260]
3080 [R(int) =
0.0313]
2676 [R(int) =
0.0245]
2263 [R(int) =
0.0605]
4107 [R(int) =
0.0291]
0.0643]
Reflections observed
2062
2896
2799
2391
1860
3693
(
>2sigma)
Data Completeness
0.99
0.92
1.00
0.99
0.99
1
Absorption correction
Semi-empirical
from equivalents
Semi-empirical
from equivalents
Semi-empirical
from equivalents
Semi-empirical
from equivalents
Semi-empirical
from equivalents
Semi-empirical from
equivalents
Max. and min. transmission
1.00000 and
1.00000 and
0.81391
1.00000 and
0.79329
1.00000 and
0.93527
1.00000 and
0.61764
1.00000 and 0.83575
0.32339

ACCEPTED MANUSCRIPT
Refinement method
Full-matrix least- Full-matrix least- Full-matrix least- Full-matrix least- Full-matrix least- Full-matrix least-
2
2
2
2
2
2
squares on F
squares on F
squares on F
squares on F
squares on F
squares on F
Data / restraints / parameters
Goodness-of-fit on F
2782 / 3 / 185
1.02
3483 / 0 / 198
1.04
3080 / 0 / 197
0.96
2676 / 0 / 163
1.02
2263 / 0 / 188
1.04
4107 / 4 / 271
0.94
2
Final R indices [I>2sigma(I)] R = 0.044
R = 0.043
R = 0.0319 wR
= 0.0836
R = 0.0361 wR
1
R = 0.035 wR
R = 0.050 wR
= 0.139
R = 0.060 wR
1
R = 0.030 wR =
0.077
1
1
1
2
1
2
1
2
2
1
2
wR
2
= 0.088
wR
2
= 0.106
= 0.098
1
2
R indices (all data)
R = 0.075
1
R = 0.056
1
R = 0.041 wR
R = 0.035 wR =
2
1
2
wR
2
= 0.099
wR
2
= 0.115
= 0.0867
= 0.103
= 0.147
0.080
Largest diff. peak and hole,
e.Å
0.33 and -0.28
0.57 and -0.28
0.35 and -0.20
0.38 and -0.26
0.44 and -0.60
0.45 and -0.58
-3
CCDC no.
1851312
1851313
1851318
1851319
1851320

ACCEPTED MANUSCRIPT
o
Table 2. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular interactions (Å, )
__________________________________________________________________________________________________________________________
(
a) Intramolecular hydrogen bonds
D—H···A
D—H
H···A
D···A
D—H···A
1
i
O1—H1···N2
0.88(3)
1.88(3)
2.668(2)
149(3)
(
b) Intermolecular H bonds
D—H···A
D—H
0.94(2)
0.98
0.88(2)
0.82(4)
H···A
2.02(2)
2.62
2.11(2)
2.20(4)
D···A
D—H···A
174.2(16)
158
175
168(3)
Symmetry code
1-x,2-y,-z
-x,1-y,-z
1-x,1-y,1-z
2-x,1-y,1-z
1
1
1
1
e
e
h
i
N1—Hn1···N3A
C17—H17C···N2
N1—H1···N3
N1—HN1···N3
2.955(4)
3.545(2)
2.9843(15)
3.013(3)
(
c) Y—X···π
Y—X···Cg
X···Cg
2.92
2.74
2.98
3.34
X
perp
γ
Y—X···Cg Y···Cg
1
1
1
1
e
h
h
i
C8—H8···Cg(benzo)
C13—H13···Cg(benzo)
C14—H14···Cg(thiazolyl)
C17—H17B···Cg(pyridnyl)
2.71
2.68
2.86
2.71
22.06
135
141
119
143
3.655(2)
3.5279(17) 1/2-x,-1+y,1-z
3.5374(17) 1/2-x,-1+y,1-z
1-x,-1/2+y,1/2-z
12.51
16.22
28.48
4.150(2)
1+x,y,z
a
(
d) π··π interactions
Cg(I)···Cg(J)
Cg···Cg
α
β
γ
CgIperp
CgJperp
1
1
1
1
1
e
h
h
i
Cg(thiazolyl···Cg(thiazolyl)
Cg(pyridinyl)···Cg(benzothiazolyl) 4.1602(8)
Cg(benzothiazolyl)···Cg(pyridinyl) 4.1602(8)
Cg(thiazolyl)···Cg(benzo)
Cg(benzo)···Cg(thiazolyl)
4.2103(16) 0.0(10)
37.4 37.4 3.3433(8)
30.6 28.4 3.6601(6)
28.4 30.6 3.5808(4)
27.6 26.7 3.4642(9)
3.3433(8)
3.5808(4)
3.6601(6)
1-x,1-y,-z
1-x,-y,1-z
1-x,-y,1-z
13.30(6)
13.30(6)
3.8769(13) 0.97(11)
3.8769(13) 0.97(11)
3.4357(10) -1+x,y,z
26.7 27.6 3.4357(10) 3.4642(9) 1+x,y,z
i
Cg(I) = Plane number I ; α = Dihedral Angle between Planes I and J (Deg) ; β = Angle Cg(I)-->Cg(J) ; γ = Angle Cg(I)-->Cg(J) vector and
normal to plane J (Deg) ; Cg-Cg = Distance between ring Centroids (Å) ; CgI_Perp = Perpendicular distance of Cg(I) on ring J (Å); CgJ_Perp =
Perpendicular distance of Cg(J) on ring I (Å).

ACCEPTED MANUSCRIPT
Table 3. Selected geometric parameters for 3.
a) Parameters involving Cu in the complex, 3
(
Cu1-O1
Cu1-N2
1.9529(17)
1.9458(18)
Cu1-O2
Cu1-N3
1.9064(15)
1.9788(18)
Cu1-O3
Cu---Cg
2.3902(17)
3.571
i
O1-Cu1-O2
O1-Cu1-N3
O2-Cu1-N3
N2-Cu1-N3 i 81.94(7)
N2-Cu1···Cg 87.3
89.20(7)
96.99(7)
171.31(8)
O1-Cu1-O3
O2-Cu1-O3
O3-Cu1-N2
O3-Cu1···Cg 162.4
O2-Cu1···Cg
83.71(6)
102.87(6)
97.23(7)
O1-Cu1-N2
O2-Cu1-N2
O3-Cu1-N3
N3-Cu1···Cg
178.48(7)
91.75(7)
83.93(7)
79.0
i
i
i
i
93.8
O1-Cu1···Cg 102.4
(
b) Ring numbers, atoms and shapes in the complex 3
Ring
Atoms in ring
Ring shape
Ring 1
Cu1,N2,N1,C2,N3
Slight twist on Cu1-N2
Pucker parameters: Q(2) = 0.0754(17) Å, Phi(2) = 20.6(16)
o
Ring 2
Ring 3
Ring 4
Ring 5
Ring 6
S1,C2,N3,C4,C9
Cu1,O2,C12,C11,C10,N2 Essentially planar
C4-C9
C11-C16
Essentially planar
Essentially planar
Essentially planar
Essentially planar
S1,C2,N3,C4-C8
(
c) Comparison of selected parameters in the ligand, 1d, and complex, 3
Complex, 3
Ligand, 1d
Complex, 3
Ligand ,1d
N1-N2
N1-C2
C2-N3
C12-C11
S2-04
S2-O3
1.389(2)
1.351(3)
1.304(3)
1.419(3)
1.4427(17)
1.4386(18)
112.99(17)
1.395(2)
1.299(2)
1.338(3)
1.410(3)
-
C10-N2
C12-O2
C11-C10
N3-C4
1.288(3)
1.329(3)
1.433(3)
1.404(3)
1.4510(16)
1.284(2)
1.352(2)
1.444(6)
1.414(3)
-
S2-O5
-
N2-N1-C2
111.61(15)
N1-C2-N3
121.11(19)
121.68(19)

ACCEPTED MANUSCRIPT
C11-C10-N2
123.3(2)
122.47(17)
N1-N2-C10
118.10(18)
114.91(15)

ACCEPTED MANUSCRIPT
o
Table 4. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular interactions for 3 (Å, )
__________________________________________________________________________________________________________________________
(
d) Intramolecular hydrogen bonds
D—H···A
D—H
H···A
D···A
D—H···A
C5—H5···O1
0.93
2.42
3.154(3)
135
(
e) Intermolecular H bonds
D—H···A
O1—H1···O5
N1—Hn1···O4 0.81(3)
O1—H2···O2
C7—H7···F3
D—H
0.805(19)
H···A
1.88(2)
2.03(3)
1.93(2)
2.48
D···A
D—H···A
177(3)
171(3)
167(3)
168
Symmetry code
2-x,1-y,1-z
-1+x,y,z
2-x,1-y,1-z
1-x,-y,-z
2.679(2)
2.837(2)
2.696(2)
3.399(3)
3.141(3)
0.78(2)
0.93
C10—H10···O5 0.93
2.42
134
-1+x,y,z
a
(
f) Y—X···π interactions
a
Y—X···Cg
X···Cg
Xperp
γ
Y—X···Cg
Y···Cg
Symmetry code
C17—F2···Cg3 3.4020(16) 3.181
20.77 125.28(12)
4.312(2)
a
Cg3 is centroid of ring with atoms [Cu1,O2,C12,C11,C10,N2].
a
π···π interactions
CgI···CgJ
Cg···Cg
α
β
γ
CgIperp
CgJperp
Symmetry code
Cg5···Cg1
Cg5···Cg2
Cg1···Cg3
Cg1···Cg5
Cg2···Cg5
Cg3···Cg1
Cg3···Cg3
Cg4···Cg4
Cg4···Cg6
Cg6···Cg4
3.5520(12)
3.7280(13)
3.9719(11)
3.5520(12)
3.7280(13)
3.9719(11)
3.4887(11)
3.8010(13)
3.8468(12)
3.8469(12)
2.68(10)
0.66(11)
3.67(8)
2.68(10)
0.66(11)
3.67(8)
0.00(8)
0.00(11)
0.20(9)
0.20(9)
17.4 17.3 3.3910(10) 3.3890(8)
26.3 25.9 3.3534(10) 3.3410(9)
1-x,1-y,1-z
1-x,1-y,1-z
1-x,1-y,1-z
27.8 31.3 3.3954(8)
17.3 17.4 3.3890(8)
25.9 26.3 3.3409(9)
31.3 27.8 3.5145(8)
3.5146(8)
3.3909(10) 1-x,1-y,1-z
3.3534(10) 1-x,1-y,1-z
3.3954(8)
3.4588(8)
1-x,1-y,1-z
1-x,1-y,1-z
7.5
7.5
3.4587(8)
24.2 24.2 3.4669(10) 3.4669(10) 1-x,-y,-z
25.8 25.7 3.4660(10) 3.4626(7) 1-x,-y,-z
25.7 25.8 3.4626(7) 3.4660(10) 1-x,-y,-z