Coordination Chemistry of Cu²⁺ Complexes of Small N-Alkylated Tetra-azacyclophanes with SOD Activity

Abstract

A new tetraaza-pyridinophane macrocycle (L1) N-alkylated with two isopropyl and one methyl groups symmetrically disposed has been prepared and its behavior compared with those of the unsubstituted pyridinophane (L3) and the related compound with three methyl groups (L2). The protonation studies show that, first, a proton binds to the central methylated amine group of L1, while, second protonation leads to a reorganization of the protons that are at this stage attached to the lateral isopropylated amines. The X-ray structure of [HL1] agrees with the UV-vis and NMR studies as well as with the results of DFT calculations. The stability of the Cu complexes decreases on increasing the bulkiness of the alkyl substituents of the amine groups. The crystal structures of [CuL1Cl](ClO) and [CuL1(HO)](ClO)·HO show square pyramidal coordination geometries with the ligands disposed in a bent L-shaped conformation. Kinetic studies indicate that the rates of both complexation and ligand dissociation decrease with the bulkiness of the substituents, so that the stability changes are surely the results of compensating effects, complex formation dominating over complex dissociation. The pH dependence of the rate constants for complex formation cannot be explained by consideration of rapid pre-equilibria involving the different protonated forms of the ligand, and it has been interpreted in terms of a mechanism involving an acid-base equilibrium for a reaction intermediate. NBT SOD studies show that the Cu complex of the bulkiest L1 ligand is the one having the highest activity (IC = 0.26(5) μM, k = 13.7 × 10 M s) which can be associated with the poorer σ-donor ability of the tertiary amino groups, and the rigidity of the system, caused by the bulky isopropyl groups.

Stabilisation of Exotic Tribromide (Br3−) Anions via Supramolecular Interaction with a Tosylated Macrocyclic Pyridinophane. A Serendipitous Case

“…It was later in the spotlight for its ability to form metal complexes [6][7][8], but its wider success was achieved thanks to its utilisation as a scaffold for the preparation of new materials that have proven effective in a variety of applications. Indeed, L derivatives decorated with different hanging functionalities have been studied for several biomedical (MRI contrast agents [9][10][11][12], antiproliferative treatments [13][14][15][16], radiotherapy [17,18], enzyme mimicking [19,20] and antioxidant activity [21][22][23]), chemosensing [24][25][26][27] and catalytic [28][29][30][31][32][33] applications. Very recently, (MRI contrast agents [9][10][11][12], antiproliferative treatments [13][14][15][16], radiotherapy [17,18], enzyme mimicking [19,20] and antioxidant activity [21][22][23]), chemosensing [24][25]…”

“…Anion-π interactions were also found to play an important role in the formation of highly organised polyiodide complexes [44,45] and iodide based permutable organised frameworks (POF) [46] with a pyridinium-based ligand such as Stoddart's blue box (BB, cyclobis(paraquat-p-phenylene)). (MRI contrast agents [9][10][11][12], antiproliferative treatments [13][14][15][16], radiotherapy [17,18], enzyme mimicking [19,20] and antioxidant activity [21][22][23]), chemosensing [24][25][26][27] and catalytic [28][29][30][31][32][33] applications. Very recently, it has been shown that L and its N-trimethylated derivative are capable of stabilising iodine-dense three-dimensional networks that might be relevant for crystal engineering purposes and the design of solid-state conductors [34].…”

Stabilization of Supramolecular Networks of Polyiodides with Protonated Small Tetra-azacyclophanes

“…− anions, each lying on the crystallographic planes ( Figure 7). The ligand assumes a bent conformation, typical of small macrocycles incorporating rigid aromatic units [22][23][24]26,27], which can be described by the 84 • dihedral angle between the aromatic ring plane and the mean plane defined by the aliphatic nitrogen atoms. The acidic protons are located on the benzylic nitrogen atoms [22][23][24], yet their interaction with the polyiodide anions are very limited, consisting of a sole contact, and moreover quite long to be considered a typical salt bridge (N2(H2A) anions define a slightly distorted void cubic lattice hosting the countercations.…”

“…The synthesis of the compounds 3,6,9-triaza-1(2,6)-pyridinecyclodecaphane (L1•3HBr) [39][40][41][42], 6-(N-methyl)-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane (L1-Me•3HBr) [42], 3,6,9-tris(N-methyl)-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane (L1-Me 3 •3HCl) [43][44][45] (Figure 3) 4-methyl-1,7-bis(p-tolylsulfonyl)-1,4,7-triazaheptane (2•3HCl) [23,42] and 4-benzyloxy-2,6-bis(bromomethyl)pyridine (py-obn) [46][47][48] (Figure 13) were carried out following the procedure described previously in the literature. All reagents were obtained from commercial sources and used as received.…”

“…Other helpful insights were drawn from the structure of the hydrobromic salt of 3,6,9-triaza-1(2,6)-pyridinecyclodecaphane (L1) which became the starting point of current work [22]. As can be seen from Figure 2, the marked basicity of the ligand [22][23][24] (the extra aza-type nitrogen helping to compensate for the loss of basicity due to the proximity of charged groups compared to the azacyclophane used in [21]) pairs with its small size, so that even in the case of the significantly smaller (compared to I − ) bromide, only one anion can be accommodated above the macrocycle; yet it may not engage all N atoms into salt-bridge/hydrogen bonding (Figure 2a To accommodate all the necessary counterions, the ligand is forced to use its ammonium groups as divergent binding sites, so that further bromide anions can be trapped within three-dimensional cavities formed in between the ligand molecules ( Figure 2c). This was considered as an indication of the ability of this ligand to force the localization of charged species outside its cage and stabilize them in three-dimensional supramolecular networks.…”