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Consecutive histidine repeats are chosen both by nature and by molecular biologists due to their high affinity towards metal ions. Screening of the human genome showed that transcription factors are extremely rich in His tracts. In this work, we examine two of such His-rich regions from forkhead box and MAFA proteins—MB3 (contains 18 His) and MB6 (with 21 His residues), focusing on the affinity and binding modes of Cu2+ and Zn2+ towards the two His-rich regions. In the case of Zn2+ species, the availability of imidazole nitrogen donors enhances metal complex stability. Interestingly, an opposite tendency is observed for Cu2+ complexes at above physiological pH, in which amide nitrogens participate in binding. Electronic supplementary material The online version of this article (10.1007/s00775-017-1512-x) contains supplementary material, which is available to authorized users.

The thionucleoside 2-thiocytidine (C2S) as well as the thiouridines (US) occur in Nature, especially in transfer RNAs, and they also receive attention in diverse fields like nanotechnology and drug research. If (C2)O in cytidine (Cyd) is replaced by (C2)S to give the thio analogue C2S, the release of H+ from (N3)H in H(C2S)+ (pKa = 3.44) is facilitated somewhat [H(Cyd)+; pKa = 4.24], yet, the deprotonation of the (C4)NH2 group is much more affected: the pKa decreases from ca. 16.7 in Cyd to 12.65 in C2S. This is because the amino-thione tautomer dominating in the neutral C2S, transfers into the imino-thioate form, which has the charge largely localized on (C2)S−. As a consequence, the M(C2S)2+ species (M2+ = Zn2+ or Cd2+) transfer very easily into their deprotonated M(C2S − H)+ forms. This reaction is extremely facilitated by M2+coordination at (C2)S− and occurs already at a pH slightly above 3. It is shown that the (C2)S M2+ coordination dominates to more than 99% in both the M(C2S)2+ and the M(C2S − H)+ complexes; their structures, including chelate formation with the participation of N3, are evaluated. In 2-thiouridine (U2S), 4-thiouridine (U4S), and 2,4-dithiouridine (U2S4S), the release of H+ from (N3)H, compared to Urd (pKa = 9.18), is facilitated by ca. 1 to 2 pK units, the charge being largely localized on the (C)S sites; this leads with (U4S − H)− and (U2S4S − H)− to the reduction of Cu(II) to Cu(I), transforming the thiolate into a disulfide. In Cu(U2S − H)+ Cu(II) is stable, most likely due to steric constraints inhibiting disulfide formation. The stability of the M(US − H)+ complexes with Ni2+, Cu2+ or Cd2+ is enhanced by about 1.3 to 2 log units compared to the corresponding uridinate complexes. The properties of the biologically relevant Zn(US − H)+ are expected to be between those with Ni2+ and Cd2+. The relatively high affinity of the (C)S sites for these M2+ is reflected in the 2-thiouridine 5′-monophosphate (U2SMP2−) and 4-thiouridine 5′-monophosphate (U4SMP2−) complexes, M2+ being located to more than 99% at the thiouracil residue and only traces are coordinated at the phosphate group. In the N3-deprotonated Cu[(U2S − H)MP]− species the anti conformer is partly turned into the syn one allowing thus a formation degree of about 60% of the macrochelate formed by (C2)S− and the phosphate group. The corresponding coordination pattern also seems to hold for Cd[(U2S − H)MP]−, though the formation degree of the macrochelate is lower. No macrochelate formation is detected for Ni[(U2S − H)MP]−, as well as for Ni[(U4S − H)MP]− and Cd[(U4S − H)MP]−. The reasons for the indicated coordination patterns are discussed, as well as the biological implications of the summarized results, especially with regard to tRNAs.

A series of linear tetrapeptides containing two histidyl residues in position 2 and 4, namely DHGH, DHGdH, KHGH, KHGdH, Ac-DHGH-NH(2), Ac-DHGdH-NH(2), Ac-KHGH-NH(2), and Ac-KHGdH-NH(2), were synthesized and characterised. Their copper(II) binding properties were investigated in depth through a variety of physicochemical methods. Potentiometric titrations were first carried out to establish the stoichiometry and the stability of the resulting copper(II)-peptide complexes. The copper(II) chromophores that are formed in the various cases in dependence of pH were subsequently characterised by extensive spectroscopic analysis (UV-Vis, EPR, CD) in strict correlation with potentiometric data. The effects of the nature of the first amino acid (Lys versus Asp) and of N-terminal amino group protection on copper(II) binding were specifically addressed. On turn, the careful comparison of the copper(II) coordination abilities of the linear peptides with those of their cyclic analogs provided insight into the effects of cyclization on the overall metal binding properties.

Cu 2+ complexes with peptides containing three histidine residues have very specific metal binding abilities and can mimic the structures of various multi-histidine metal binding sites in proteins. The main goal of the work concerns the investigations of coordination abilities of the group of N-terminally protected Ac-His-Arg-His-Gly-His-Gly, Ac-His-Gly-His-Arg-His-Gly, Ac-Gly-His-His-Arg-His-Gly and Ac-His-His-Gly-His-Arg-Gly, and their unprotected analogs His-Arg-His-Gly-His-Gly, His-Gly-His-Arg-His-Gly, Gly-His-His-Arg-His-Gly and His-His-Gly-His-Arg-Gly towards Cu 2+ ions. Detailed spectroscopic (UV/Vis, CD and EPR) and potentiometric studies have been made. The stoichiometry and binding mode for each ligand–Cu 2+ system were determined. In the case of N-terminally protected peptides the coordination begins at the imidazole nitrogen(s) which act as the anchoring groups. At physiological pH the {3N im , 2N − } binding pattern is suggested and at high pH three amide nitrogens are involved in Cu 2+ binding. According to the coordination abilities of the unprotected peptides, the position of the histidine residue determines the coordination mode. For His 1 peptides the histamine-like {NH 2 , N im } mode for the first species is suggested. The final albumin-like coordination mode is proposed not only for HGHRHG and HRHGHG but also for GHHRHG. For ligands with the His-Xaa-His motif the {2N − , 2N im } binding mode is formed easier. For ligands with His 2 the 3N complex with the {NH 2 , N − , N im } binding pattern is a dominant species within the physiological pH range. The protection of the amine group caused a significant decrease of the coordination abilities of the peptides.

The formation of the molecular assemblies consisting of anionic and cationic molecules may lead to their interesting structural properties. In this work, we present three new structures based on the tetradentate oxime and amide open-chain ligand CH3– C(@NOH)–C(O)–NH–(CH2)3–NH–C(O)–C(@NOH)–CH3 (PAP). All the structures contain the complex cations, complex anions [M(PAP-3H)] � and solvating water molecules. These are H-bonded complex anions: [Ni(1,3-pn)2(H2O)2][Ni(PAP-3H)]2 AE 4H 2 O( 1), [Ni(Im)4(H2O)2][Ni(PAP-3H)]2 (2) and [Cu(Im)4(H2O)2][Cu(PAP-3H)]2 AE 2H2 O( 3) (Im ¼ imidazole; 1-3-pn ¼ 1,3-diaminopropane). All compounds were synthesised by co-crystallisation of octahedral amine-containing cationic complex with oxime-containing anionic complexes in methanol solution. They were compared with some earlier reported assemblies based on the same ligand (PAP). The comparison of the structures reveals one distinct difference in the separation between the cis-situated oximate oxygen atoms O(1) �� � O(4) in the copper complexes. The consequence of this effect is the lengthening of the Cu–N distances. In the nickel complexes containing [Ni(PAP-3H)] � anion this effect is much less pronounced.

Complex formation properties of a novel water soluble thiazolyloxime 2-(4-methylthiazol-2-yl)-2-(hydroxyimino)acetic acid (H3L1) with Cu2+ and Ni2+ were investigated in solution by potentiometrical and spectral (UV–Vis, EPR, NMR) methods. All Cu2+ and most of Ni2+ complex species detected in solution were found to have square-planar MN4 core with oxime and heterocyclic nitrogen atoms which was rationalized in terms of destabilizing effect of repulsive interaction between oxygen atom of carboxylic group and nitrogen atom of thiazole ring in N,O-coordinated ligand conformation. It has been found that stability of metal complexes in a series of oxime ligands is dependent upon basicity of nitrogen atom of oxime group. The thiazolyloxime forms less stable complexes with Cu2+ but stronger ones with Ni2+ ions when compared to parent 2-(hydroxyimino)propanoic acid. The lower stability obtained for Cu2+ complexes was elucidated in terms of negative inductive effect of the thiazole and nitrile substituents as well as an effect of intramolecular attractive interaction between thiazolyl sulfur and oxime oxygen atoms in thiazolyloxime. In the case of Ni2+ the complexes formed are square-planar and it is why thiazolyl ligand is more effective in metal ion binding than simple 2-(hydroxyimino)propanoic acid forming only octahedral species. The solid state structure of the Co3+ complex K3[Co(HL1)3]·5.5H2O (1) was studied by X-ray analysis. The thiazolyloxime ligand is coordinated to Co3+ via oxime nitrogen and carboxylate oxygen atoms forming five-membered chelate rings.

Solution (potentiometric, absorption, EPR) as well as solid state studies (X-ray, EPR, magnetic susceptibility) have shown that the binding ability of oxalodihydroxamic acid (H2oxha) with two hydroxamic groups next to each other differs distinctly from that observed for aliphatic dihydroxamic acids, HONHOC(CH2)nCONHOH (n = 3–8). H2oxha was found to be a very powerful ligand for NiII and CuII due to an N,N′-chelating binding mode. The availability of the mixed nitrogen–oxygen donor systems results in formation of polymeric complexes with CuII. The crystal structure of K2[Ni(oxha)2]·2H2O has shown two very characteristic features of the dihydroxamic ligand: (i) two short intramolecular hydrogen bonds stabilising very effectively the complex formed and (ii) very specific binding modes of K+ ions, which play a bridging role between [Ni(oxha)2]2− ions. The latter finding demonstrates a capacity of H2oxha-based anionic complex species to form polynuclear complexes with different bridging modes.

The centrosymmetric neutral mononuclear title complex, [Ni(C5H5N2O3)2(C2H8N2)2]·6H2O, has the Ni centre in a distorted octa­hedral environment, defined by six N atoms belonging to two chelating ethyl­enediamine mol­ecules and two cyano N atoms derived from cyanoxime ligands. The O atom of the deprotonated oxime group forms hydrogen bonds with two solvent water mol­ecules.

The title compound, (C2H10N2)2[Ni(C2HN2O4)2].2H2O, has an ionic structure containing a centrosymmetric complex 4- anion, charge-balancing ethylenediaminium dications and solvent water molecules. The oxalohydroxamate unit is triply deprotonated and forms five-membered chelate rings with the central Ni ion; the Ni ion lies on an inversion centre. The two hydroxamate O atoms in the complex anion are linked by short intramolecular hydrogen bonds.

Potentiometric spectroscopic and X-ray studies of the open chain oxime ligand, N,N′-bis(2-hydroxyimino-propionyl)propane-1,3-diamine and its complexes with NiII and CuII ions showed a very high efficacy of the ligand studied in the co-ordination of both CuII and NiII ions. The metal complexes are very stable and square-planar with four nitrogens involved in metal-ion binding. These complexes may be additionally stabilised by hydrogen bonds between two oxime oxygen atoms.

The study on the binding ability of tested ligands have shown that insertion of two dehydro-amino acid residues into peptide sequences makes them more effective in metal ion binding than ligands with one dehydro-amino acid residue. The ligand with two Z(Delta)Phe residue form more stable complexes than his analogues with one Z(Delta)Phe residue. Interesting is this that position of Z(Delta)Phe residue in peptide chain have impact on Cu(II)-complexes formation.