Cu(II) and Ni(II) complexes of n (2 hydroxybenzyl) amino acid ligands synthesis, structures, properties and catecholase activity 2

In fact, the two copper atoms of dicopperII bio-active centers present in different metalloenzymes are found to act cooperatively within the proximity of ~3.5 Ǻ with each CuII centre coo

Chapter 2

Dinuclear Copper(II) Complexes as

Functional Models for the Catechol

Oxidase

2-1 Prelude to Parts A and B

Next to iron, copper is the most important bioessential element and its biological

relevance is recognized to the highest degree in the last decades due to the rapid

development of bioinorganic chemistry which offers a successful interaction between

model complexes and metalloenzyme chemistry Transport, activation and

metabolism of dioxygen are very important processes in living systems

Metalloenzymes containing one or more copper centers are responsible for these

functions Many copper containing metalloenzymes such as hemocyanin (dioxygen

carrier), tyrosinase (hydroxylation of monophenols and melanin pigment formation),

catechol oxidase (oxidation of catechols), dopamine β-hydroxylase (production of

catecholamine for nerve and metabolic function), superoxide dismutase (disposal of

potentially damaging radicals formed during normal metabolism), plastocyanin of

plant chloroplasts (electron transport for photosynthesis), celuroplasmin (potential

extra cellular free radical scavenger) and other enzymes such as tryptophan

oxygenase, ascorbate oxidase have been discovered.1-4

Proteins containing dinuclear copper centers play paramount roles in biology,

including dioxygen transport or activation, electron transfer, reduction of nitrogen

oxides and hydrolytic chemistry.5 Copper proteins are classified as Type 1, Type 2

and Type 3 Among them many copper enzymes have oxidase or oxygenase activities

Type 3 copper proteins are characterized by an antiferromagnetically coupled

dicopper core with three histidine ligands on each copper ion and µ-hydroxo bridging

in the met Cu(II)-Cu(II) form which results in the EPR silent active site Among the

well-known representatives of Type 3 copper proteins, catechol oxidase with active

dicopper(II) sites is a ubiquitous enzyme in living systems for catalyzing the oxidation

of a wide range of ortho-diphenols (catechols) to ortho-diquinones (Figure 2-1) The

subsequent auto polymerization of the highly active quinones into polyphenolic

catechol melanins is considered to be responsible for the defense mechanism observed

in plants against pathogens or pests.6 While tyrosinase catalyzes the hydroxylation of

tyrosine to dopa (cresolase activity) and the oxidation of dopa to dopaquinone

(catecholase activity) with electron transfer to dioxygen, catechol oxidase exclusively

catalyzes the oxidation of catechols to quinones without acting on tyrosine. 7 This

reaction is of great importance in medical diagnosis for the determination of the

hormonally active catecholamines adrenaline, noradrenaline and dopa.8 Oxidation of

mono- and diphenol-containing neurotransmitters such as dopamine, epinephrine,

norepinephrine and serotonin have been found associated with the Fe(II) and Cu(II)

centered redox chemistry related to Alzheimer’s disease.8b-d

Figure 2-1 Catecholase reaction in natural systems

In fact, the two copper atoms of dicopper(II) bio-active centers present in different

metalloenzymes are found to act cooperatively within the proximity of ~3.5 Ǻ with

each Cu(II) centre coordinated by three histidine donors.5 As confirmed by the recent

X-ray crystal structure analysis, catechol oxidase in the met oxidized form contains

the dicopper active centers with a Cu···Cu distance of 2.9 Å.9

The crystal structure of catechol oxidase reported recently by Krebs and co-workers

shown in Figure 2-2 reveals new insight into the functional properties of the Type III

copper protein which includes the closely related and well known tyrosinase as well

as hemocyanin.9a These proteins have a dinuclear copper center and have similar

spectroscopic behavior and functional relationships

Figure 2-2 Overall structure of catechol oxidase from sweet potato (ipomoea

batatas) Copper atoms are shown in orange, α helices in blue, β sheets in green.9a

One of the interesting structural aspects encountered in the active site of catechol

oxidase from sweet potatoes (Ipomoea batatas) and in the active sites of some

hemocyanins is an unusual thioether bond between a carbon atom of one of the

histidine ligands and the sulfur atom of a nearby cysteine residue from the protein

backbone A cysteinyl-histidinyl bond has also been reported for other Type 3 copper

proteins such as tyrosinase from Neurospora crassa,10a and hemocyanin from Helix

pomatia10b and Octopus dofleini.10c A thioether bond between cysteine and tyrosine is

also present in the mononuclear copper enzyme galactose oxidase.10d Biomimetic

models mimicking this unique feature were reported by Belle and Reedjik10e and

Wieghart and co-workers.10f In an attempt to further mimic this quite unusual

structural feature, recently, Krebs et al demonstrated that adjacent thioether group

enhanced the activity of dicopper(II) complexes by weakening the exogenous acetate

bridging.11h

Figure 2-3 Oxy and met forms during the activity of tyrosinase and/or catechol

oxides

Based on the spectroscopic and biochemical evidences as well as the recent X-ray

crystallographic structural findings of catechol oxidase,9 a plausible mechanism has

been proposed for catecholase activity of tyrosinase and /or catechol oxidase.9a, 12 The

catalytic cycle begins with the oxy and met states A diphenol substrate binds to the

met state, followed by the oxidation of the substrate to the first quinone and the

formation of the reduced state of the enzyme Binding of the dioxygen leads to the oxy

state which is subsequently attacked by the second diphenol molecule Oxidation to

the second quinone forms the met state again and closes the catalytic cycle Thus, in

short, the catecholase activity of tyrosinase and catechol oxidase is carried out by the

oxy form (Cu(II)-O22--Cu(II)) and by the met form (Cu(II)-Cu(II)) of the enzymes

through a two electron-transfer reaction as shown in Figure 2-3 Coordination sphere

of the dinuclear copper center in the met state is shown in Figure2-4.9a

Figure 2-4 Coordination sphere of the dinuclear copper center in the met state.9a

In order to gain deeper insight into the copper-mediated substrate oxidations and to

understand the influence of various parameters that determine bimetallic reactivity

both in natural metalloenzymes and in synthetic analogues, studies of the well defined

and appropriate dicopper(II) complexes are obviously essential For this reason, quite

a number of mono- and dinuclear copper(II) complexes have been investigated as

biomimetic catalysts for catechol oxidation.11-14 Krebs and Reimdemonstrated that

that complexes with strained structures show catalytic activity, whereas complexes

present in relaxed and energetically favored conformations are essentially inactive

towards catechol oxidation.11j

Krebs et al have shown the dicopper(II) complex [Cu2bbpen](ClO4)2.3MeOH as a

structural and functional model for catechol oxidase.14a In all the modeling studies,

11-14 a common and convenient model substrate, 3,5-DTBC, has been employed as a

model substrate (Figure 2-5) since its low redox potential makes it easy to oxidize,15

and the bulky substituents prevent further side reactions such as ring opening

Figure 2-5 Biomimetic oxidation of 3,5-DTBC catalyzed by dicopper(II) complex

Figure 2-6 Formation of 3,5-DTBQ band from the oxidation of 3,5-DTBC catalyzed

by [Cu2bbpen2](ClO4)2·3MeOH The inset shows the course of the absorption

maximum at 405 nm with time for 10 and 100 equivalents of 3,5-DTBC.14a

Further, the oxidation product, 3,5-DTBQ is sufficiently stable and displays a strong

absorption at ca λmax = 390 nm the growth of which can be monitored by UV-Vis

spectroscopy as shown in Figure 2-6.14a

For a dicopper(II) complex to act as an efficient catalyst towards the oxidation of

3,5-DTBC, a steric match between substrate and complex is believed to be the

determining factor: two metal centers have to be located in the proximity of 3 Å to

facilitate proper binding of the two hydroxyl oxygen atoms of catechol prior to the

electron transfer.16 (Figure 2-7) This view is supported by the observation that

dinuclear copper complexes are generally more active towards the oxidation of

catechol than the corresponding mononuclear complexes.16 Further, Nishida et al

have shown that square-planar mononuclear copper(II) complexes are less active than

non-planar mononuclear copper(II) complexes.17

Figure 2-7 Proposed steric match and binding of substrate with complex.

With dinuclear copper(II) complexes, only a few structurally characterized

complex/substrate adducts are reported The first, described by Karlin et al.18 was

prepared by the oxidative addition reaction from a phenoxo-bridged dicopper(II)

complex and tetrachloro-o-benzoquinone (tcbq) which displayed a bridging

tetrachlorocatechol (tcc) between the two copper(II) ions with a Cu···Cu distance of

3.248 Å Recently, crystal structures of the different adducts of complex/substrate

exemplifying various coordination modes of catecholate have been reported as shown

in Figure 2-8.19

Figure 2-8 TCBQ complexes, [HL3Cu2(TCC)(H2O)2]2.ClO4 (left) and

[HL Cu (TCC)(H O)] ClO (right) as models for substrate binding.19b

Comparing the activity of a series of dicopper(II) complexes containing various

endogenous and exogenous bridging moieties, Mukherjee and Mukherjee reported

that nature of the bridging group has profound effects on the ability of the complexes

to perform the oxidation.20 It has been assumed that for the square pyramidal

dicopper(II) complex to act as an active catalyst, the dissociation of bridging

group/axial donor must occur so that a vacant coordination site will be readily

available for the binding of substrate in a bridging mode As the binding strength of

exogenous bridge decreases, the ability of the complex to bind to the substrate

increases and the oxidation becomes more efficient The compounds [Cu2(L5

-O)2(OClO3)2] (L5-OH = 4-methyl-2,6-bis(pyrazol-1-ylmethyl)phenol) (Figure 2-9

(left)) was found inactive, probably the bridging structure changes due to reaction

with catechol.20

Figure 2-9 Dicopper(II) complexes studied by Mukherjee et al (left)20a and Jager et

al (right).11f

The complex,

{1,2-O-isopropylidene-6-N-(3-acetyl-2-oxobut-3-enyl)amino-6-deoxy-glucofuranoso}copper(II) (Figure 2-9 (right) reported by Jager et al has been

found to be highly active among the model complexes. 11f These investigations also

confirmed that the copper(II) complexes are reduced to copper(I) complexes during

catalysis and electron transfer from catechol to the copper(II) complex begins after the

formation of a copper-catechol intermediate which could be prevented by the

competitive formation of copper-quinone complex.16

Reactivity of the dicopper(II) complexes towards catechols have established both

geometry around the copper(II) ions and Cu···Cu distance as two key factors in

determining the catalytic ability of the complexes.11f, 20-21 The short Cu···Cu distance

allows the bridging catechol coordination compatible with the distance between the

two o-diphenol oxygen atoms.11f, 20-21 Jager and Klemm 11f proposed a mechanism

which was adapted from Karlin22 and Casella23 as shown in Figure 2-10 In this

mechanism, dinuclear copper(I) species with the o-quinone, µ-peroxo moieties with

copper(II) are the key intermediates

Figure 2-10 Mechanism of 3,5-DTBC oxidation catalyzed by dicopper(II)

complexes.11f

Neves et al.24 postulated a mechanism for the pH dependent oxidation of

3,5-DTBC by the acetato-bridged complex [Cu2(H2bbppnol)(µ-OAc)(H2O)2]Cl2.2H2O

According to the proposed mechanism (Figure 2-11), in the first step, a

pre-equilibrium exists between the complex and its deprotonated form since the reaction

depends on pH

As the incoming catecholate is stronger than acetate, acetate is replaced by the

coordinating diphenol as a bridging ligand prior to the intramolecular electron-transfer

reaction The electron-transfer reaction, as the rate-determining step, results in the

oxidation of catechol substrate to the corresponding o-quinone and the reduction of

copper centers to copper(I) The oxidation of Cu(I)-Cu(I) complex with 4-coordinated

Cu(I) centers back to the original form in the presence of dioxygen completes the

catalytic cycle as shown in Figure 2-11

Figure 2-11 Proposed mechanism for the pH dependent oxidation of 3,5-DTBC by

acetate bridged complex, [Cu2(H2bbppnol)(µ-OAc)(H2O)2]Cl2.2H2O.24

Torelli et al investigated a series of µ-OH dicopper(II) complexes25 (for example,

[Cu2(LR)(μ-OH)](ClO4)2) (LR =

(2,6-bis[{bis(2-pyridylmethyl)amino}-methyl]-4-R-substituted phenol, R = -OCH3, -CH3, -F) as model systems for the catechol oxidase

regarding the binding of catechol substrate in the first step of the catalytic cycle It is

shown that ortho-diphenol binds monodentately one copper(II) center with the

concomitant cleavage of the OH bridge The mechanism shown in Figure 2-12

displays the substrate fixation step as the first step: the first adduct corresponds to the

one proposed by Krebs12c and the other adduct corresponds to the one proposed by

Solomon.12a

Figure 2-12 Proposed mechanism for the interaction between dinuclear copper(II)

µ-OH complexes and the 3,5-DTBC.25 Insert: (A) intermediate proposed by Krebs;12c

(B) intermediate proposed by Solomon.12a

The complete deprotonation of the monodentate bound catechol leads to a bridging

catecholate prior to the electron transfer The µ-OH appears to be a key factor to

achieve the complete deprotonation of the catechol, leading to a bridging catecholate

This view is further supported when Belle and Reedjik demonstrated the effect of

substituting the µ-hydroxo bridge with chloride or bromide ion.10e Upon substitution

of the µ-hydroxo bridge with the halogen anion, no proton transfer occurred

precluding the binding of catecholate in bidentate bridging fashion, and thus the

subsequent catalytic cycle

Many attempts to establish a correlation between the structural parameters of the

complexes and their catalytic activity in the oxidation of catechols were described in

the literature.11-14, 16-25 Some of the crucial factors dictating the catecholase activity

can now be highlighted based on these investigations made on the dicopper(II)

complexes: the distance between the Cu(II) centres,21 the nature of the bridging group

between the copper ions,10, 20 electronic properties of the complexes 21a and the

geometric changes of the dicopper core.19b Furthermore, the factors such as the

number of donor sites, nature of the donors and the rigidity of the ligand or the

bridging moiety imposing strain in the complex have also been found to play a role.11j

Chapter 2

Part A

Synthesis, Characterization, Structural Properties and Catecholase Activity of Dicopper(II) Complexes of reduced Schiff

base Ligands

2-A-1 Introduction

In this section, we present a series of dicopper(II) complexes of reduced Schiff base ligands formed between various substituted salicylaldehydes and

aminocyclopentane/cyclohexanecarboxylic acids and L-alanine (Chaper 1, Figure

1-20, p-31) Driven by our recent results demonstrating the effect of the chelating side arms of the dicopper(II) complexes,27 we are prompted to investigate the role of electron-donating and withdrawing groups at the benzene ring of the ligand on catecholase activity Despite the plethora of the reports on catecholase activity of various dicopper(II) complexes, studies modulating the activity in terms of electronic properties21 via substituted bridging phenolates have not been well documented Such

investigation on the structure-reactivity patterns is essential to enhance the mechanistic understanding of the parameters affecting the catecholase activity This section describes the structural features and catecholase activity of the dicopper(II) complexes of various reduced Schiff base ligands containing substituted phenolate moiety Further, variable temperature magnetic studies on the representative complex have also been discussed

2-A-2 Results and Discussion

2-A-2-1 Synthesis

The dinuclear copper(II) complexes, [Cu2(RScp11)2(H2O)2] [R = H (IIA-1), Cl (IIA-2), CH3 (IIA-3), OH (IIA-4)], [Cu2(RSch11)2(H2O)x] [R = H and x = 1 (IIA-5),

R = Cl (IIA-6), R = CH3 and x = 2 (IIA-7)], [Cu2(RSch12)2(H2O)2] [R = H (IIA-8),

CH3 (IIA-10), [Cu2(ClSch12)2].2H2O (IIA-9)], [Cu2(Diala5)(H2O)2].H2O, IIA-11;

[Cu2(Diala4)(H2O)2].H2O, IIA-12 and [Cu2(Diala3)(H2O)2].H2O, IIA-13 have been

synthesized in good yields by the complexation of copper(II) acetate monohydrate or

copper(II) nitrate trihydrate with the corresponding reduced Schiff base ligands

according to the procedures described in the experimental section Owing to their

poor solubility in common solvents except in DMF and DMSO, our attempts to get

single crystals of the bulk as such were not successful However, for [Cu

-2(Scp11)2(MeOH)2] (IIA-1a), [Cu2(ClScp11)2(DMF)(H2O)].MeCN (IIA-2a),

[Cu2(MeScp11)2(MeOH)2].2MeOH (IIA-3a), [Cu2(ClSch11)2(MeOH)2].2MeOH

[Cu2(Diala4)2(DMSO)2]⋅2DMSO⋅2Acetone, IIA-12a the single crystals with the

solvates different from bulk were obtained following the technique of slow diffusion

of solvents (see experimental section) But the complexes IIA-4 and IIA-8 afforded

single crystals from the reaction mixture as described in the experimental section

2-A-2-2 Description of crystal structures

In all these complexes, the reduced Schiff base ligands display tridentate

coordination mode with binucleating ability through bridging phenolate oxygen

atoms The ONO donor set arising from amine nitrogen, phenolate oxygen and one of

the carboxylate oxygen atoms completes the tridentate coordination of the ligands to

the Cu(II) ions (Figure 2-13) All these complexes contain phenolato bridged

dinuclear Cu2O2 cores with Cu···Cu distance of ca 3 Å With respect to the ligands,

IIA-1a, IIA-2a, IIA-3a and IIA-4 contain 1-aminocyclopentanecarboxylate side arm

as a common structural moiety but different substituents on the 5-position of the

benzene ring; H in IIA-1a, Cl in IIA-2a, CH3 in IIA-3a and OH in IIA-4 All these

complexes, IIA-1a, IIA-2a, IIA-3a, IIA-4 and IIA-12a display Cu(II) centres with

distorted square pyramidal geometry (τ = 0.168, 0.043, 0.038, 0.228 and 0.003

respectively)28 while square planar Cu(II) centers are present in IIA-9a

Crystallographic centre of inversion is present in the dimeric structure of 1a, 3a, IIA-4, IIA-6a and IIA-9a

IIA-Figure 2-13 Schematic representation of dicopper(II) complexes The axial positions

are mostly occupied by the solvents

In all these complexes, basal plane of the square pyramid is completed by the coordination of each Cu(II) to the two bridging phenolate oxygen atoms, amine nitrogen and carboxylate oxygen The Cu-O bond distances due to the coordination of each Cu(II) to the bridging phenolate and carboxylate oxygen atoms in the basal plane fall in the range of 1.934(2)-2.002(3) Å and 1.876(2)-1.982(7) Å respectively while the bond distances due to Cu-N (amine nitrogen) are observed in the range of

1.950(2)-2.004(8) Å The apical position is occupied by aqua ligands as in IIA-4, by solvent molecules such as methanol as in IIA-1a and by both aqua ligand and DMF solvent as in IIA-2a giving the Cu-O bond distances in the range 2.213(2)-2.660(3) Å The common 1-aminocyclopentanecarboxylate side arm of the ligands in IIA-1a, IIA-2a, IIA-3a and IIA-4 resulted in the formation of five membered rings where as

the bridging phenolate oxygen generated four membered Cu2O2 rings

The crystal packing of dimers in IIA-1a, IIA-2a, IIA-3a and IIA-12a resulted in

the formation of 1D hydrogen bonded polymeric structures while the packing pattern

in IIA-4 resulted in the 3D hydrogen bonded network structures

2-A-2-2-1 [Cu2 (Scp11)2(MeOH) 2], IIA-1a

The complex IIA-1a as a methanol adduct crystallized with two methanol

molecules in monoclinic system with space group C2/c with Cu···Cu separation of 3.0245(7) Å Selected bond lengths and bond angles are given in Table 2-1 The apical positions of square pyramid of the two Cu(II) atoms are occupied by methanol

molecules in trans fashion (Figure 2-14)

Figure 2-14 A perspective view of the dimer, IIA-1a

Table 2-1 Selected bond distances (Å) and bond angles (º) for IIA-1a

C(1)-O(1)-Cu(1) 118.37(18) Cu(1)a-O(1)-Cu(1) 101.04(9)

Symmetry transformations used to generate equivalent atoms: a = -x+1,-y+1,-z+1

Complementary MeOH···O=C (O4-H4···O2) and N-H···O=C (N1-H1···O3) intermolecular hydrogen bonding generates 1D polymeric structure in the solid state (Figure 2-15) Table 2-2 contains the hydrogen bond parameters

Figure 2-15 A view showing a portion of the 1D hydrogen-bonded structure in

IIA-1a

Table 2-2 Hydrogen bond distances (Å) and angles (º) for IIA-1a

D-H d(D-H) d(H··A) ∠DHA d(D··A) A Symmetry

N1-H1 0.80(3) 2.35(4) 148(4) 3.053(3) O3 x-1, y, z-½

O4-H4 0.72(4) 1.97(4) 174(5) 2.691(4) O2 x-1, y, z-½

2-A-2-2-2 [Cu2 (ClScp11) 2(DMF)(H2O)] MeCN, IIA-2a

Each Cu(II) atom adopts distorted square pyramidal geometry The two copper atoms in the dimer are separated by distance of 3.0428(6) Å Selected bond lengths and bond angles are given in Table 2-3 The apical site of square pyramid is occupied

by DMF [Cu(1)-O(8), 2.230(3) Å] with Cu(1) and aqua ligand [Cu(2)-O(7), 2.299(3)

Å ] with Cu(2) in trans to each other Each dimer is associated with a molecule of

acetonitrile solvent in the asymmetric unit (Figure 2-16)

Figure 2-16 A perspective view of the unit cell contents of IIA-2a

Table 2-3 Selected bond distances (Å) and bond angles (º) for IIA-2a

generates 1D polymer along the b-axis (Figure 2-17) sustained by hydrogen bonds

between carboxylate oxygen and aqua ligand, O(7) H(7B)···O(3) Further H(7A)···N(4S) hydrogen bonds have also been observed Hydrogen bond parameters are shown in Table 2-4

O(7)-Figure 2-17 Hydrogen bonded association in IIA-2a

Table 2-4 Hydrogen bond distances (Å) and angles (º) for IIA-2a

D-H D(D-H) d(H··A) ∠DHA d(D··A) A Symmetry

O7-H7A 0.73(6) 2.26(4) 162(6) 2.961(9) N4S x+1, y, z

O7-H7B 0.81(6) 1.92(4) 177(5) 2.728(4) O3 x-1, y-1, z-1

2-A-2-2-3 [Cu2 (Mescp11)2 (MeOH)2].2MeOH, IIA-3a

The complex IIA-3a displays square pyramidal geometry at each Cu(II) centre

(Figure 2-18) Basal plane of square pyramid is occupied by two phenolate oxygen atoms [Cu(1)-O(1) 1.960(2) Å and Cu(1)-O(1A) 1.944(2) Å], amine nitrogen [Cu(1)-N(1) 1.961(2) Å] and the carboxylate oxygen [Cu(1)-O(2) 1.939(2) Å] Table 2-5 shows the selected bond distances and bond angles

Figure 2-18 A perspective view of IIA-3a

The apical sites the square pyramid at each Cu(II) centre are occupied by methanol

molecules in trans fashion with Cu···O distance of 2.59 Å The two square planar

copper centres resulted in the Cu···Cu distance of 3.0056(5) Å through phenolate bridging

Table 2-5 Selected bond distances (Å) and bond angles (º) for IIA-3a

Symmetry transformations used to generate equivalent atoms: a = -x+1,-y+1,-z+1

Packing of dimers along a axis displays intermolecular hydrogen bonding between

amine hydrogen and lattice methanolic oxygen (N-H···O(5)) and also between methanolic hydrogen and carboxylate oxygen atoms (O(4)-H(4)···O(3) and O(5)-H(5)···O(2)) Carboxylate oxygen atoms of the neighboring molecules involved in

weak interactions with each Cu(II) ion in syn-anti fashion giving the Cu···O distance

of 2.885 Å Hydrogen bond distances and angles are tabulated in Table 2-6 The solid state structure of this compound is a 1D polymer supported by all these interactions (Figure 2-19)

Table 2-6 Hydrogen bond distances (Å) and angles (º) for IIA-3a

D-H D(D-H) d(H··A) ∠DHA d(D··A) A Symmetry

N1-H1 0.87(3) 2.10(3) 159(3) 2.932(3) O5 -x,-y+1,-z+1

O4-H4 0.76(4) 2.05(4) 163(3) 2.785(3) O3 x+1, y, z

O5-H5 0.78(6) 2.14(5) 156(5) 2.864(4) O2

Figure 2-19 Packing diagram of IIA-3a

2-A-2-2-4 Crystal structure of [Cu 2 (OHScp11) 2 (H 2 O) 2 ], IIA-4

Figure 2-20 A perspective view of the dimer IIA-4

The crystal structure of IIA-4 consists of the basic dimeric building block

[Cu2(OH)Scp11)2(H2O)2] in which both Cu(II) centres have square pyramidal geometry The two lattice water molecules are in close interaction with Cu(II) atoms

with Cu-O distance of 2.66(3) Å occupying the apical positions to complete the square pyramidal geometry around each Cu(II) centre (Figure 2-20) The two Cu(II) atoms bridged by the two phenolate oxygen atoms resulted Cu···Cu distance of 2.9924(8) Å Table 2-7 shows the selected bond lengths and angles

Table 2-7 Selected bond distances (Å) and bond angles (º) for IIA-4

O(1)a-Cu(1)-N(1) 165.21(9) O(1)a-Cu(1)-O(4) 105.32(8)

Symmetry transformations used to generate equivalent atoms: a = -x+1,-y+1,-z+1

Packing of the dimers along b axis showed one of the aqua ligands involving in the

hydrogen bonding with the oxygen atom of the hydroxyl group on the phenolate moiety (O4-H4B···O5) and the carboxylate oxygen atom (O4-H4A···O3) N-H···O hydrogen bonds are formed between the N-H hydrogen atom and carboxylate oxygen atom (N1-H1···O3) In addition, there is also hydrogen bonding between the hydrogen atom of the hydroxyl group and oxygen atom of aqua ligand (O5-H5···O4) These

hydrogen bonds generate 3D hydrogen bonded network connectivity in IIA-4

Hydrogen bond distances and angles are shown in Table 2-8 A portion of the

hydrogen bonding connectivity in IIA-4 has been shown in Figure 21 and Figure

2-22

Figure 2-21 Packing diagram of IIA-4

Figure 2-22 A segment of H-bonded 3D network in IIA-4

Table 2-8 Hydrogen bond distances (Å) and angles (º) for IIA-4

2-A-2-2-5 [Cu 2 (ClSch11) 2 (MeOH) 2 ].2MeOH, IIA-6a

The compound IIA-6 crystallized in triclinic space group Pī with two methanol molecules in the crystal lattice and IIA-6a is isomorphous to IIA-3a i.e the

arrangement of molecules in the crystal lattice, but not isostructural The coordination geometry of each Cu(II) centre is square pyramidal geometry (Figure 2-23) with the square base occupied by two phenolate oxygen atoms [Cu(1)-O(1) 1.970(2) Å and Cu(1)-O(1A) 1.951(2) Å], amine nitrogen [Cu(1)-N(1) 1.968(2) Å] and the carboxylate oxygen [Cu(1)-O(2) 1.940(2) Å]

Figure 2-23 A perspective view of IIA-6a

The apical positions of square pyramid at each Cu(II) centre are occupied by

methanol molecules in trans fashion with Cu···O distance of 2.492 Å The two copper

atoms are bridged by two phenolic oxygen atoms giving the Cu···Cu distance of 3.0380(5) Å Selected bond parameters are given in Table 2-9

Table 2-9 Selected bond distances (Å) and bond angles (º) for IIA-6a

O(1)-Cu(1)a 1.951(1) Cu(1)-Cu(1A)a 3.0382(5)

O(2)-Cu(1)-O(1)a 103.62(6) O(2)-Cu(1)-N(1) 83.76(7)

O(1)a-Cu(1)-N(1) 169.91(7) O(2)-Cu(1)-O(1) 173.62(6)

O(1)a-Cu(1)-O(1) 78.49(6) O(2)-Cu(1)-Cu(1)a 142.78(5)

Symmetry transformations used to generate equivalent atoms: a = -x+1,-y+1,-z+1

Hydrogen bonding pattern in IIA-6a is similar to that observed in IIA-3a The solid

state crystal packing along b axis revealed that the complex is a 1D polymer resulting

from the Cu···O weak interactions and intermolecular hydrogen bonding (Figure 24)

2-Figure 2-24 Packing diagram of IIA-6a

Further, carboxylate oxygen atoms of the neighboring dimeric units maintain weak

interactions with each Cu(II) ion (Cu···O, 2.95 Å) in syn-anti mode In addition to

these interactions, crystal packing also reveals that N-H hydrogen atoms involve in the intermolecular hydrogen bonding to methanolic oxygen atoms (N(1)-H(1)···O(5)) and the methanolic hydrogen atoms maintain intermolecular hydrogen-bonding to carboxylate oxygen atoms (O(4)-H(4)···O(3) and O(5)-H(5)···O(2)) Hydrogen bond parameters are given in Table 2-10

Table 2-10 Hydrogen bond distances (Å) and angles (º) for IIA-6a

D-H d(D-H) d(H··A) ∠DHA d(D··A) A Symmetry

N1-H1 1.01(3) 1.92(3) 167(2) 2.905(3) O5

O4-H4 0.71(3) 2.08(3) 171(4) 2.775(2) O3 x-1, y, z

O5-H5 0.75(3) 2.11(3) 169(3) 2.851(3) O2 -x+2, -y+1, -z+1

2-A-2-2-6 [{Cu2(Sch12)2}2 ⋅Cu 2(Sch12)2(H2O)2].4H2O, IIA-8

For Z = 3 in the triclinic space group Pī, there are three independent Cu(II)-Sch12

units each one is near inversion centres (½, ½, ½), (0,0,0) and (½, ½, 0) in IIA-8 as

illustrated in Figure 2-25 Of these Cu3 has an aqua ligand in the apical position The O9 of the carboxylate group from this unit is bonded to Cu2 with Cu2-O9 distance, 2.513(13) Å Table 2-11 shows selected bond lengths and bond angles Similarly O6 occupies the apical axial position of the Cu1 (Cu1-O6, 2.355(12) Å) having distorted square pyramidal geometry On the other hand, the oxygen atom of the third carboxylate group, O3 is only involved in hydrogen bonding to a hydrogen atom, H13D of lattice water Hydrogen bond parameters are given in Table 2-12

Figure 2-25 Perspective view of the unit cell contents in IIA-8 The lattice water

molecules are omitted for clarity

Figure 2-26 Portion of packing diagram of IIA-8 showing the 2D connectivity The

hydrogen atoms and lattice water molecules have been omitted for clarity

The axial bonding of the carbonyl oxygen atoms O6 and O9 from neighboring dimeric units to Cu1 and Cu2 centres produces a 2D coordination polymeric structure

and the interdimer connectivity leads to the formation of 2D (4, 4) network structure

as shown in Figure 2-26 and these (4, 4) nets are well known in coordination polymeric structures.29

Table 2-11 Selected bond distances (Å) and bond angles (º) for IIA-8

O(2)-Cu(1)-O(1)a 94.9(5) O(1)-Cu(1)-O(1)a 76.8(6)

O(1)a-Cu(1)-N(1) 154.7(6) O(1)a-Cu(1)-O(6) 111.8(5)

O(5)-Cu(2)-O(4)b 96.8(5) O(4)b-Cu(2)-O(4) 76.1(5)

O(4)b-Cu(2)-N(2) 161.0(6) C(15)-O(4)-Cu(2)b 133.4(10)

Cu(2)b-O(4)-Cu(2) 103.9(5) O(7)c-Cu(3)-O(7) 78.1(6)

O(7)c-Cu(3)-N(3) 163.4(6) Cu(3)c-O(7)-Cu(3) 101.9(6)

O(7)c-Cu(3)-O(11) 95.0(5)

Symmetry transformations used to generate equivalent atoms: a = -x+1,-y+1,-z+1; b =

-x,-y,-z; c = -x+1,-y+1,-z

Table 2-12 Hydrogen bond distances (Å) and angles (º) for IIA-8

D-H d(D-H) d(H··A) ∠DHA d(D··A) A

2-A-2-2-7 [Cu 2 (ClSch12) 2 ].2MeOH, IIA-9a

The crystal structure of IIA-9a reveals that the complex crystallized in space group

Pī with each Cu(II) centre displaying square planar geometry as shown in Figure 2-27 Selected bond lengths and bond angles are given in Table 2-13 Each Cu(II) ion completes the square planar geometry by coordinating through two bridging phenolate oxygens

Table 2-13 Selected bond distances (Å) and bond angles (º) for IIA-9a

O(1)a-Cu(1)-N(1) 165.17(9) O(2)-Cu(1)-Cu(1)a 132.51(6)

Symmetry transformations used to generate equivalent atoms: a = -x+1,-y+1,-z+1

Figure 2-27 A view of the unit cell contents of IIA-9a

The unit cell contains two methanol molecules involved in hydrogen bonding via

amine nitrogen [N(1)-H(1)···O(1S)] and carboxylate oxygen [O(1S)-H(1S)···O(3)] which lead to the formation of 1D polymeric structure (Figure 2-28)

Figure 2-28 A portion of the 1D structure formed between IIA-9 and methanol

molecules IIA-9a

The hydrogen bond distances observed in the solid state packing of IIA-9a are

found to vary between 1.90 and 2.38 Å Table 2-14 contains selected hydrogen bond parameters These hydrogen bonds are considered to be normal as compared to the available literature on N-H···O and O-H···O hydrogen bond parameters.30

Table 2-14 Hydrogen bond distances (Å) and angles (º) for IIA-9a

D-H d(D-H) d(H··A) ∠DHA d(D··A) A Symmetry

N1-H1 0.84(4) 2.03(4) 171(3) 2.866(4) O1S

O1S-H1S 0.79(4) 1.89(4) 166(5) 2.667(4) O3 -x+1, -y+1, -z

2-A-2-2-8 [Cu 2 (Diala4) 2 (DMSO) 2 ] ⋅2DMSO⋅2Acetone, IIA-12a

The dimer crystallized with four DMSO molecules of which two are bonded at the apical positions of each Cu(II) in the dimer and two are hydrogen-bonded to the amine hydrogen atoms through N-H⋅⋅⋅O interactions as shown in Figure 2-29 The two

DMSO molecules are disposed in anti fashion This causes the dimer to have a

pseudo-center of inversion which is unprecedented in these types of structures having chiral reduced Schiff base ligands.26 Ribbon like 1D hydrogen bonded polymeric structure produced by complementary O-H⋅⋅⋅O bonds between phenolic hydrogen and oxygen atoms of the carboxylate group as displayed in Figure 2-30 and all these polymers are aligned parallel to (1ī0) plane (Figure 2-31) Acetone molecules filled the empty cavities between these strands

Figure 2-29 A perspective view of IIA-12a

Selected bond parameters and hydrogen bond parameters are given in Table 2-15 and Table 2-16 respectively

Table 2-15 Selected bond distances (Å) and bond angles (º) for IIA-12a

Figure 2-30 A portion of H-bonded 1D polymer in IIA-12a

Figure 2-31 Packing pattern in IIA-12a

Table 2-16 Hydrogen bond distances (Å) and angles (º) for IIA-12a

N1-H1 0.92 2.11 153 2.96(1) O11

N2-H2 0.92 2.08 146 2.89(1) O12

O7-H7 0.83 1.87 164 2.68(1) O3 x+1, y+1, z

O8-H8A 0.83 1.93 154 2.70(1) O6 x-1, y-1, z

2-A-3 Physico-chemical studies

2-A-3-1 Infrared spectra

The IR absorption bands of the complexes IIA-1 - IIA-13 in the range of

3398-3458 cm-1 indicate the presence of coordinated or lattice water molecules,31a, 31c further supported by the weight loss observed in TG The sharp bands observed in the range of 2927-2960 cm-1 are due to ν(N-H) The absorption bands observed in the region of 1597-1640 cm-1 and 1360-1460 cm-1 are due to the asymmetric [νasCOO-] and symmetric [νsCOO-] stretching frequencies respectively The stretching frequencies characteristic of [ν(C–O)] are observed in the range of 1262-1272 cm-1 The difference (Δν) between [νasCOO-] and symmetric [νsCOO-] has been used to determine their binding mode in the metal complexes.31a In general, Δν for monodentate carboxylate is greater than 200 cm-1 and for a bridging carboxylate Δν is less than 200 cm-1.31a, 32 This observation has been confirmed for the 2D coordination

polymeric structure in IIA-8 showing bridging (Δν = 115 cm-1) mode of carboxylate

Furthermore, the crystal structure of IIA-8 displays the syn-anti mode of bridging for

the carboxylate group The structures of Cu(II) complexes involving the carboxylate

in syn-anti mode of bridging exist in literature.31f – I Selected IR bands are given in Table 2-17

Table 2-17 IR spectral data of IIA-1 - IIA-13

Complex υ(OH) υ(NH) υas(COO-) υs(COO-) υ(CO)

2-A-3-2 Electronic spectra

Electronic spectra of the complexes IIA-1 - IIA-13 recorded in DMF solution and

nujol mull are shown in Table 2-18 The absorption bands observed in the range

620-703 nm correspond to d-d transitions and strong bands at 358-402 nm are due to

ligand-to-metal charge transfer For an octahedral geometry the expected 2Eg to 2T2g

transition takes place at around 800 nm This band will undergo a significant blue shift when octahedral geometry distorts to square pyramidal and square planar structure.33 For the reduced Schiff base copper(II) complexes with square pyramidal

geometry, the d-d transitions and charge transfer transitions generally occur in the

range 620-720 nm and 360-450 nm respectively.27, 34

Table 2-18 Magnetic and UV-Vis data of IIA-1 - IIA-1

Absorption bands (DMF) (Nujol)

CT bands to higher energies.21b, 34d Accordingly, we observe the electron donating

para –CH 3 group shifting LMCT band to lower energy and the electron withdrawing

para –OH and –Cl groups causing the shift of LMCT band to higher energy Based on

the crystal structure of IIA-9a, the geometry around the copper(II) centers in IIA-9 is

assumed to have square planar geometry The observed d-d transitions in IIA-9 at 623

nm also indicate square planar Cu(II) centers This behavior is similar to those recorded for the structurally well characterized square planar copper(II) complexes.33

The electronic spectra of IIA-1 – IIA-13 do not change much in DMF solution and

nujol mull, and appear to indicate that the coordination number and geometry observed in solid state are retained in solution

2-A-3-3 ESI-MS studies

The structural behavior of the complexes IIA-1 - IIA-13 in solution has been

investigated by ESI mass spectral analysis ESI mass spectra of the complexes were

recorded in MeOH except for IIA-2, IIA-7 and IIA-9 for which the spectra were

recorded in a 1:1 solvent mixture of MeOH and DMSO due to solubility problem As indicated by the masses of both positive and negative ions in the spectra, all the complexes are found to exist in solution mainly as dicopper(II) species (Table 2-19)

For example, the positive ion ESI masses observed for IIA-8 shows (Figure 2-32) the

existence of dicopper(II) species predominantly in solution as [Cu2(Sch12)2Na]+ (643, 100) The other less intense peaks found were [Cu(Sch12)Na]+ (333, 27); [Cu3(Sch12)3Na]+ (954, 55); [Cu4(Sch12)4Na]+ (1267, 25); [Cu5(Sch12)5Na]+ (1574, 20) Our attempts to obtain the consistent electrochemical data using CV were unsuccessful owing to the solubility problem Nonetheless, it may be noted that the concentration levels in methanolic solutions were just enough for the activity studies

Figure 2-32 ESI-MS of IIA-8

Table 2-19 ESI-MS data of IIA-1 - IIA-13

Complex Solvent Principal molecular species

(m/z), % peak height) a

[Cu2(Scp11)2 H] + (594.1 100); [Cu2(Scp11)2Na] + (614,80); [Cu 3 (Scp11) 3 Na] + (912, 52); [Cu 4 (Scp11) 4 H] + (1188.8, 25); [Cu4(Scp11)4Na] + (1208, 80);

[Cu 5 (Scp11) 5 Na+] (1504, 40); [Cu 6 (Scp11) 6 Na+] (1803.5, 30)

IIA-2 MeOH/DMSO [Cu 2 (ClScp11) 2 H]+ (699, 100);

[Cu(ClScp11)2(DMSO)Na] + (699.1, 50); [Cu 2 (ClScp11) 2 (DMSO)H]+ (818.4, 20); [Cu3(ClScp11)3(DMSO)H] + (1152.7, 22);

[Cu4(ClScp11)3(DMSO)4] + (1370.7, 52);

IIA-3 MeOH [Cu 2 (MeScp11) 2 (CH 3 OH)Na] + (678.9, 100);

[Cu2(MeScp11)3] - (870.1, 20); [Cu3(MeScp11)4] - (1179.9, 28); [Cu 4 (MeScp11) 5 ] - (1492.0, 30) [Cu2(MeScp11)2(CH3OH)H] + (654.9, 28);

IIA-4 MeOH [Cu 2 (OHScp11) 2 ] - (623.1, 100); [Cu(OHScp11) 2 ] -