Dopamine Interaction in the Absence and in the Presence of Cu²⁺ Ions with Macrocyclic and Macrobicyclic Polyamines Containing Pyrazole Units. Crystal Structures of [Cu₂(L₁)(H₂O)₂](ClO₄)₄ and [Cu₂(H_-1L₃)](ClO₄)₃·2H₂O

Abstract

The interaction with Cu2+ and dopamine of three polyazacyclophanes containing pyrazole fragments as spacers is described. Formation of mixed complexes Cu2+−macrocycle−dopamine has been studied by potentiometric methods in aqueous solution. The crystal structures of the complexes [Cu2(L 1)(H2O)2](ClO4)4·2H2O (4) (L 1 = 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.111,14]octacosa-1(27),11,14(28),24-tetraene) and [Cu2(H- 1 L 3)](HClO4)(ClO4)2·2H2O (6) (L 3 = 1,4,7,8,11,14,17,20,21,24,29,32,33,36-tetradecaazapentacyclo[12.12.12.16,9.119,22.131,34]hentetraconta-6,9(41),19(40),21,31,34(39)-hexaene) are presented. In the first one (4), each Cu2+ coordination site is made up by the three nitrogens of the polyamine bridge, a sp2 pyrazole nitrogen and one water molecule that occupies the axial position of a square pyramid. The distance between the copper ions is 6.788(2) Å. In the crystal structure of 6, the coordination geometry around each Cu2+ is square pyramidal with its base being formed by two secondary nitrogens of the bridge and two nitrogen atoms of two different pyrazolate units which act as exobidentate ligands. The axial positions are occupied by the bridgehead nitrogen atoms; the elongation is more pronounced in one of the two sites [Cu(1)−N(1), 2.29(2) Å; Cu(2)−N(6), 2.40(1) Å]. The Cu−N distances involving the deprotonated pyrazole moieties are significantly shorter than those of the secondary nitrogens. The Cu(1)···Cu(2) distance is 3.960(3) Å. The pyrazole in the noncoordinating bridge does not deprotonate and lies to one side of the macrocyclic cavity. One of the aliphatic nitrogens of this bridge is protonated and hydrogen bonded to a water molecule, which is further connected to the sp2 nitrogen of the pyrazole moiety through a hydrogen bond. The solution studies reveal a ready deprotonation of the pyrazole units induced by coordination to Cu2+. In the case of L 2 (L 2 = 3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.111,14]octacosa-1(27),11,14(28),24-tetraene), deprotonation of both pyrazole subunits is already observed at pH ca. 4 for 2:1 Cu2+:L 2 molar ratios. All three free receptors interact with dopamine in aqueous solution. L 3 is a receptor particularly interesting with respect to the values of the interaction constants over five logarithmic units at neutral pH, which might suggest an encapsulation of dopamine in the macrocyclic cage. All three receptors form mixed complexes Cu2+−L−dopamine. The affinity for the formation of ternary dopamine complexes is particularly high in the case of the binuclear Cu2+ complexes of the 1-benzyl derivative L 1.

Hochempfindliche Erkennung von Substraten adrenerger Rezeptoren an der Luft‐Wasser‐Grenzschicht

“…[4] Neuere Entwicklungen auf dem Gebiet der künstlichen Catecholamin-Rezeptoren beruhten auf Bipyridinium-Goldnanopartikel-Anordnungen, [5] Phenylboronaten [6] und pyrazolhaltigen Kryptanden. [7] Mit RNA-Aptameren [8] oder kupferhaltigen Redoxenzymen [9] wurden bioorganische Alternativen vorgestellt. Ausgehend von der natürlichen Bindungseinheit [10] haben wir einen künstlichen Adrenalinrezeptor mit folgenden Erkennungseinheiten entwickelt: 1) eine p-Xylylenbisphosphonat-Einheit dient als etablierte Aminoalkohol-bindende Funktion [11] mit ausreichender Beweglichkeit für einen "induced fit"; 2) an diese zentrale Einheit sind starre Bausteine gebunden, die für eine hohe Präorganisation sorgen.…”

Cu2+-Induced formation of cage-like compounds containing pyrazole macrocycles

“…[4][5][6] The first of these receptors L 1 takes up, both in solution and in the solid state, two Cu 2+ metal ions. Its X-ray structure revealed a strongly distorted square pyramidal coordination geometry around each copper centre.…”

“…The Cu(1)-Cu(2) distance of 3.967 Å falls within the range found for related complexes. † [4][5][6]8 Scheme 1…”

Zn(II) Coordination by Open-chain Polyamine Ligands Containing Dipyridine Units. Highly Active Dinuclear Zn(II) Complexes in Phosphate Ester Hydrolysis

“…Polyamine ligands containing six or more nitrogen donors and cavities of appropriate shape and dimension may be able to hold two metal centers at short distances [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The distance between the two metal ions can be varied by an opportune synthetic modulation of the structural characteristics of the ligands.…”