Srećko I. Kirin

Systematizing structural motifs and nomenclature in 1,n′-disubstituted ferrocene peptides

Ferrocene peptide conjugates display an array of structural features including helical ferrocene based chirality and a number of different intramolecular hydrogen bonding patterns. In this tutorial review we present a rigorous nomenclature for these systems, followed by a section that summarises and categorises the structures known to date. The issues discussed herein are of general relevance for all metallocene-based chiral transition metal catalysts and peptide turn mimetics.

Synthesis, structure and comparison of the DNA cleavage ability of metal complexes M(II)L with the N-(2-ethoxyethanol)-bis(2-picolyl)amine ligand L (M = Co, Ni, Cu and Zn)

Complexes of a N,N-bis(2-picolyl)amine (bpa) derivative with a pendant ethoxyethanol side chain (bpa(CH2)2O(CH2)2OH) (1) with late divalent transition metal ions Co(II), Ni(II), Cu(II) and Zn(II) have been studied. All complexes, [[bpa(CH2)2O(CH2)2OH]Co(NO3)](NO3) (1Co), [[bpa(CH2)2O(CH2)2OH]Ni(NO3)](NO3) (1Ni), [[bpa(CH2)2O(CH2)2OH]Cu(H2O)(NO3)](NO3) (1Cu) and [[bpa(CH2)2O(CH2)2OH]Zn(NO3)](NO3) (1Zn), were comprehensively characterized and their X-ray single crystal structures have been determined. The complexes show hexacoordinated geometries, in which 1 acts as a tetradentate (1Cu) or pentadentate (1Co, 1Ni and 1Zn) ligand. DNA cleavage experiments have been performed on supercoiled double stranded DNA plasmids in order to compare the cleavage efficiency of all four metals in the same ligand environment of 1. In this assay, 1Co and 1Cu showed the highest cleavage efficiency, whereas 1Ni and 1Zn were virtually inactive. Quantification of the gel electrophoresis bands showed that more than 80% of the plasmid has suffered at least one single strand cut in the case of 1Cu, and about 50% of the plasmid was nicked by 1Co. The differential cleavage activity is discussed in relation to the structural findings and a mechanism is proposed for 1Cu.

Unsymmetrical 1,n′-disubstituted ferrocenoyl peptides: convenient one pot synthesis and solution structures by CD and NMR spectroscopy

We present a systematic study on unsymmetrical amino acid derivatives of 1,1′-ferrocene dicarboxylic acid. A convenient and general one pot synthetic procedure is presented in which the unsymmetrical amino acid derivatives are readily separated by column chromatography. The following ferrocene derivatives Fe[C5H4-CO-Aaa1-OMe][C5H4-CO-Aaa2-OMe] with different amino acids were prepared and their solution structures studied by NMR and CD spectrosocopy (Aaa1 = Aaa2 = Phe, 1; Aaa1 = Aaa2 = DPhe, 1a; Aaa1 = Aaa2 = Ala, 2; Aaa1 = Phe, Aaa2 = Ala, 3; Aaa1 = DPhe, Aaa2 = Ala, 4; Aaa1 = Aaa2 = Pro, 5; Aaa1 = Aaa2 = Gly, 6; all amino acids are pure L enantiomers except where stated otherwise). NMR spectroscopy in CDCl3 confirms intramolecular hydrogen bonds for the disubstituted derivatives 1–4 and 6. CD spectra were recorded for all derivatives in CH2Cl2. They clearly show a P helical isomer of the ferrocene moiety for the L amino acid derivatives 1–3 and M helicity for the DPhe derivative 1a. The racemic derivative 6 shows only intermolecular interactions, while the Pro derivative 5, which is devoid of amide protons, most likely exists in an “open conformation”. Most importantly, the unsymmetrical mixed D,L derivative 4 has only a weak CD signal in the ferrocene region which is interpreted as an equilibrium between the P and M helical isomers with a slight excess of the latter.

Reversible site-specific tagging of enzymatically synthesized RNAs using aldehyde–hydrazine chemistry and protease-cleavable linkers

The investigation of RNA structure, dynamics and biological function often requires the site-specific incorporation of non-natural moieties. Here we describe the functionalization of RNA transcripts by aldehyde–hydrazine chemistry using a simple initiator nucleotide that carries an acetal-protected aldehyde function. This initiator nucleotide was efficiently incorporated into RNA, and the modified RNAs were quantitatively coupled to a peptide derivative displaying a hydrazine moiety at one end, a biotin tag at the other, and a trypsin-cleavable sequence in between. RNA conjugates could be easily isolated by affinity chromatography on streptavidin agarose and quantitatively cleaved off the support by trypsin treatment without detectable RNA degradation. The strategy described here may allow the incorporation of various new features into enzymatically synthesized RNA under mild conditions.

The application of “backdoor induction” in bioinspired asymmetric catalysis

Amino acid substituted monodentate triphenylphosphine ligands Lig-Aa1-Aa2-Aa3-Z 5 and 6, with a C-terminal ester or amide group, respectively, were prepared in a few simple synthetic steps. Supramolecular in situ formed complexes [Rh(COD)(Lig-Aa1-Aa2-Aa3-Z)2]BF43 and 4 with a prochiral coordination sphere of the metal are selective hydrogenation catalysts (up to 68% ee). The selectivity is induced by transmission of chirality via distant hydrogen-bonded amino acids with a Herrick-like secondary structure (“backdoor induction”).

Diels–Alder reactions of C-phenylated siloles with 1,4-epoxy-1,4-dihydronaphthalene

Abstract Preparation of a novel type of cycloadducts composed of a 7-silanorbornene ring condensed to the 7-oxanorbornene moiety ( 5 – 7 ) is described and their spectroscopic features are discussed in detail. The X-ray data for 5 are also presented. Finally, formation of silanole 8 by nucleophilic cleavage of an endocyclic silicon–carbon bond in 7 is described.

Two similar lactone-hydrochlorides with different types of hydrogen bonding networks: Crystal structure of (R,S)-α-amino-γ-caprolactone hydrochloride and racemic α-amino-γ-methyl-γ-valerolactone hydrochloride semihydrate

The X-ray crystal structure of (R,S)-α-amino-γ-caprolactone hydrochloride (compound1) and α-amino-γ-methyl-γ-valerolactone hydrochloride semihydrate (compound2) are presented. Both compound1 and compound2 belong to the orthorhombic system. Caprolactone-hydrochloride1 crystallizes in the space groupP212121 witha=5.1948(7),b=8.7404(8),c=17.907(1) Å.V=813.0(2) Å3,Z=4. Valerolactone-hydrochloride2 crystallizes in the space groupP na21 witha=26.771(8),b=5.1598(7),c=13.201(3) Å,V=1823.5(7) Å3,Z=8. The lactone cations maintain the same, open envelope conformation in both crystals. The lactone-hydrochloride packing arrangements in1 and2 are distinctly different. While in1 N−H...Cl and N−H...O hydrogen bonding creates two dimensional nets in the form of puckered layers perpendicular to the [001] direction, in2 a water molecule of crystallization with an additional OW−H...Cl hydrogen interaction assists in forming a three-dimensional hydrogen-bond network throughout the crystal.