Ralf Alsfasser

Ni(II), Cu(II) and Zn(II) complexes of a bifunctional bis(picolyl)amine (bpa) ligand derived from glycine

Abstract The reactions of the tripodal ligand bpaAc–Gly–OEt (1a) (bpaAc–Gly–OEt=(N,N-bispicolylamino)acylglycine ethyl ester) with three different transition metal dihalides MCl2 (M=Ni, Cu, Zn) have been studied. 1a is a typical member of a new family of quadridentate amino acid derived ligands developed in our laboratories. X-ray crystal structures of the products [(bpaAc–Gly–OEt)NiCl2] (2), [(bpaAc–Gly–OEt)CuCl]2[(H2O)CuCl3]Cl·3H2O (32[(H2O)CuCl3]Cl), and [(bpaAc–Gly–OEt)ZnCl]2[ZnCl4] (42[ZnCl4]) were obtained. The formation of octahedral (2), square-pyramidal (3), and trigonal-bipyramidal (4) coordination geometries demonstrates the flexibility of the quadridentate N3O ligand framework. A comparison with literature data reveals some general trends in the chemistry of our amino acid ligands with different metal ions. The ligands are designed as building blocks for larger molecular and supramolecular assemblies. This report is part of our effort to study their basic coordination chemistry in order to gain insight in structural properties of aggregates based on synthetic metallopeptides.

The reactivity of N-coordinated amides in metallopeptide frameworks: molecular events in metal-induced pathogenic pathways?

The amino acid derived tertiary amide ligand tert-butoxycarbonyl-(S)-alanine-N,N-bis(picolyl)amide (Boc-(S)-Ala-bpa, 1) has been synthesized as a model for metal-coordinating peptide frameworks. Its reactions with copper(II) and cadmium(II) salts have been studied. Binding of Cu2+ results in amide bond cleavage and formation of [(bpa)(solvent)Cu]2+ complexes. In contrast, the stable, eight-coordinate complex [(Boc-(S)-Ala-bpa)Cd(NO3)2] (5) has been isolated and characterized by X-ray crystallography. An unusual tertiary amide nitrogen coordination is observed in 5; this gives rise to significantly reduced cis-trans isomerization barriers. Possible implications for metal-induced conformational changes in proteins are discussed.

Chiral Quadridentate Ligands Derived from Amino Acids and Some Zinc Complexes Thereof

A series of three new quadridentate ligands was synthesized by reaction of the haloacetylated amino acid esters L-BrAc−Phe−OMe (4a), L-BrAc−Lys(Z)−OMe (4b), and ClAc−Gly−OEt (4c), respectively, with bis(picolyl)amine (bpa, 5). The obtained products L-bpaAc−Phe−OMe (3a), L-bpaAc−Lys(Z)−OMe (3b), and bpaAc−Gly−OEt (3c) were treated with Zn(OTf)2 (OTf = CF3SO3−) to yield the trigonal-bipyramidal complexes [(L-bpaAc−Phe−OMe)ZnOTf](OTf) (6a), [(L-bpaAc−Lys(Z)−OMe)ZnOTf](OTf) (6b), and [(bpaAc−Gly−OEt)ZnOTf](OTf) (6c). Crystal structures of 6c and the hydrolysis product [(L-bpaAc−Phe−OMe)(H2O)ZnOTf](OTf)2 (7a) are reported. The results suggest the formation of a chiral pocket at the metal center provided by the benzyl substituent in the L-phenylalanine derivative 7a. This observation is further supported by 1H-NMR and circular dichroism spectroscopic data. These methods indicate a significant ordering effect within the ligands upon metal coordination as well as interactions between the first coordination spheres and their chiral environments provided by the L-phenylalanine and L-lysine moieties of 3a and 3b, respectively. Our results are discussed with respect to the development of chiral building blocks for transition metal catalysts and biomimetic assemblies.

A peptide approach to covalently linked [Ru(bipy)3]2+–ferrocene and [Ru(bipy)3]2+–tyrosine conjugates

Abstract We have worked out the synthesis of two bifunctional photochemically active peptide derivatives based on a side chain ruthenium labeled amino acid. The ruthenium modified amino acid [H-Orn{Ru(bipy) 2 m}-OH](PF 6 ) 3 (Orn=ornithine, m=4-carbonyl-4′-methyl-2,2′-bipyridyl) was used as a module for the synthesis of a [Ru(bipy) 3 ]-(Fc-CONHR) (Fc-CONHR=ferrocene-1-carboxamide), and a [Ru(bipy) 3 ]-Tyr (Tyr=tyrosine) chromophore-quencher conjugate. The complex [Fc-Orn{Ru(bipy) 2 m}-OMe](PF 6 ) 2 shows efficient luminescence quenching by energy transfer. Electron transfer from phenolate to ruthenium occurs in the dipeptide [Boc-Tyr-Orn{Ru(bipy) 2 m}-O](PF 6 ) above pH 9. Implications for the development of cooperative sensing devices and light energy converting peptides are discussed.

Inductive Effects in Ruthenium‐Modified Amino Acids

Emission spectroscopy has been used to probe and quantify electronic interactions mediated by alkyl side chains in a homologous series of amino acids. The ω-amine functions of diaminopropionic acid (DAPA), diaminobutyric acid (DABA), ornithine, and lysine were covalently labeled with a luminescent [Ru(bipy)3]2+ fragment. Protonation of the α-amine function results in a significant dependence of nonradiative excited-state decay rates on the number of methylene groups, n, in the respective side chain. Two analogous series of compounds in which the α-amino acid moiety was replaced by R−NH2 or R−NMe3+ have been studied for comparison. It was found that the emission energies of the chromophore and the pKA values of the remote amine functional groups in our complexes are both affected by inductive effects which can be described by a Hammett−Taft type relationship. We were able to show that the induction decays with 1/n, where n = the number of methylene groups separating the chromophore from the amine and ammonium functions. A qualitative description of the phenomenon is given in terms of acid base theory.

Intramolecular Luminescence Quenching in Amino Acid Bridged Ruthenium(II)-Copper(II) Complexes with Negligible Ground-State Coupling

A series of heterobimetallic complexes [{Ru(bipy)2}m-AA{Cu(phen)(H2O)}](PF6)3 (m-AA = Nω-(4-carbonyl-4′-methyl-2,2′-bipyridyl)-L-α,ω-diamino acid; diamino acid (AA): 1b, L-2,3-diaminopropionic acid; 2b, L-2,4-diaminobutyric acid; 3b, L-ornithine, 4b, L-lysine) has been synthesized and characterized starting from the 2,2′-bipyridineruthenium(II)-substituted amino acids [{Ru(bipy)2}m-AA-αN-tBoc]2+ (αN-tBoc-1a–4a, αN-tBoc = Nα-tert-butoxycarbonyl). The metal centers in 1b–4b are bridged by insulating alkyl chains. Consequently, spectroscopic and electrochemical investi-gations confirmed the absence of any appreciable ground-state coupling between ruthenium(II) and copper(II). However, the luminescence of 1b–4b is significantly quenched compared to that of the parent compounds 1a–4a. Quenching was found to proceed only intramolecularly and to be most efficient in 1b with the shortest alkyl spacer. Equilibrium constants for the formation of 1b–4b were determined from luminescence titrations of the respective ruthenium-substituted amino acid with [Cu(phen)(NO3)2]. The complexes 2b–4b (K = 1.61–2.08 × 107M–1) were found to be significantly more stable than 1b (K = 5.7 × 106M–1). This is explained by a stronger electrostatic repulsion between the two metal centers in the latter compound.

Luminescent, Cu2+ -binding chromophore-spacer receptor conjugates derived from ruthenium-substituted lysine

Abstract Two luminescent chromophore–spacer–receptor conjugates, [H 2 cyclenAcLys{Ru(bipy) 2 m}OH](PF 6 ) 4 ( 3 ) and [mLys{Ru(bipy) 2 m}OMe](PF 6 ) 2 ( 4 ) (m=4-carbonyl-4′-methyl-2,2′-bipyridyl; bipy=2,2′-bipyridyl) were synthesized. Both compounds bind copper(II) ions in aqueous solution with concomitant quenching of their ruthenium-based emission. A pentadentate acylated cyclen ligand (cyclen=1,4,7,10-tetraazacyclododecane) is the metal binding receptor site in 3 . The conjugate 4 contains a bidentate 2,2′-bipyridyl subunit. Both compounds were prepared starting with the synthesis of the spacer–receptor subunits and subsequent coupling with the chromophore [Ru(bipy) 2 (mOSu)](PF 6 ) 2 ( 8 , HOSu= N -hydroxysuccinimide). The emission properties of 3 in aqueous solution are almost independent of the pH. Compound 4 shows a significant quenching below pH 5 which is most likely due to an electron transfer from Ru 2+ to the protonated bipyridyl ligand. Both ligands, 3 and 4 , form 1:1 complexes with copper(II) ions. Higher aggregates are only formed at substoichiometric metal ion concentrations. The complex 3 –Cu 2+ is stable over a range of pH 2–12. In contrast, the complex 4 –Cu 2+ dissociates under basic conditions above approximately pH 10. Copper(II) is rebound upon acidification making 4 the first example for a receptor which exhibits reversibility at high pH.

Selective Recognition of Copper(II) by a Water-Soluble, Emitter-Receptor Conjugate Containing a Ruthenium Chromophore, a Lysine Bridge, and a Cyclen Unit

The amino acid derivative [H-Lys{Ru(bipy)2m}-cyclenH2](PF6)5 (7; Lys = lysine, bipy = 2,2′-bipyridyl, m = 4-carbonyl-4′-methyl-2,2′-bipyridyl, cyclen = 1,4,7,10-tetraazacyclododecane) has been synthesized. A modular approach was taken which involves only standard amide-coupling methods well-known from peptide synthesis. Compound 7 is readily soluble in water. It contains a luminescent ruthenium chromophore and a cyclen ligand which serves as a binding site for metal ions. The emission of 7 is pH-independent but efficiently quenched by Cu2+ ions in a pH range of 6−7. Copper(II) binding is reversible upon protonation of the ligand at pH values below 6. In contrast, no significant spectral changes are observed with Zn2+ and Ni2+, respectively. Thus, 7 selectively recognizes copper(II) in aqueous solution under slightly acidic to neutral conditions. Unfortunately, applications at higher pH values are limited by metal-promoted hydrolysis of 7 under mildly basic conditions.

Probing the aqueous copper(II) coordination chemistry of bifunctional chelating amino acid ligands with a luminescent ruthenium chromophore

A covalently attached fluorescent [Ru(bipy)3]2+ label was used to probe the coordination chemistry of two different bpa–amino acid (bpa = bis(2-picolyl)amine) conjugates with copper(II) ions in aqueous solutions. The ligand moiety bpaAc–AA (Ac = acyl) is quadridentate and contains an O-coordinating secondary amide function. It forms a stable 1:1 complex with Cu2+ ions in a pH range between 2 and 12. This is evident from an efficient quenching of the ruthenium based emission. The Cu+/2+ redox transition is reversible. Formation of the copper(I) complex results in a restoration of the luminescence intensity. It is thereby possible to switch the emission ON and OFF by chemical reduction and oxidation with hydrazine and hydrogen peroxide, respectively. The ligand framework AA–bpa is tridentate and contains a tertiary carboxamide linkage. This functional group causes a dramatically lower affinity for copper(II) ions. A complex is only formed in a pH range between 8 and 10. The formation is slow and results in a subsequent cleavage of the tertiary amide bond. Implications for the use of both ligand moieties for the design of bioinorganic hybrid molecules are discussed.

Can aromatic interactions control the coordination geometry of zinc complexes? Structural evidence and a possible mechanism for the conversion of trigonal-bipyramidal to octahedral compounds

Aromatic interactions are well known to participate in the structural stabilization of biological macromolecules. We have utilized this motif as an unconventional new means to control the stereochemistry of synthetic zinc complexes. The aromatic amino acid L-phenylalanine has been applied as a building block in the chiral ligand bpaAc–Phe–OMe (N,N-bis(2-picolyl)aminoacyl-(S)-phenylalanine-methylester). Zinc(II) complexes of this ligand are always trigonal–bipyramidal in the solid state. This is confirmed by the X-ray structures of [(bpaAc–Phe–OMe)Zn(OTf)]+ (1b, OTf = Triflate), [(bpaAc–Phe–OMe)Zn(H2O)]2+ (2b), and [(bpaAc–Phe–OMe)Zn(pz)]2+ (3b). In contrast, the octahedral complexes [(bpaAc–Gly–OEt)Zn(pz)(OTf)]+ (3a) and [(bpaAc–Gly–OEt)Zn(N-Meim)(H2O)]2+ (4a) have been obtained with the related glycine derived ligand bpaAc–Gly–OEt. A comparison with the five-coordinate structures of [(bpaAc–Gly–OEt)Zn(OTf)]+ (1a) and [(bpaAc–Gly–OEt)Zn(Cl)]+ (5) allows an appreciation of effects brought about by (1) the coligand (chloride, triflate, pyrazole, N-methylimidazole) and (2) the non-coordinating amino acid side chain (benzyl in bpaAc–Phe–OMe). It is shown that the pyrazole complex 3b adopts an unusual tense five-coordinate geometry which is stabilized by weak aromatic interactions. The structure represents an analogue of the possible transition state between five-coordinate trigonal-bipyramidal and six-coordinate octahedral complexes in our series.