A Dinuclear Mercury(II)‐Mediated Base Pair in DNA

The first dinuclear metal‐mediated base pair containing divalent metal ions has been prepared. A combination of the neutral bis(monodentate) purine derivative 1,N⁶‐ethenoadenine (ϵA), which preferentially binds two metal ions with a parallel alignment of the N−M bonds, and the canonical nucleobase thymine (T), which readily deprotonates in the presence of Hg^II and thereby partially compensates the charge accumulation due to the two closely spaced divalent metal ions, yields the dinuclear T‐Hg^II₂‐ϵA base pair. This metal‐mediated base pair stabilizes the DNA oligonucleotide duplex as shown by an increase of 8 °C in its melting temperature. Formation of the base pair was demonstrated by temperature‐dependent UV spectroscopy as well as by titration experiments monitored by UV and CD spectroscopy.     

N‐Methyl‐2, 2'‐Dipicolylamine Complexes as Potential Models for Metal‐Mediated Base Pairs

Metal‐mediated base pairs can be used to insert metal ions into nucleic acids at precisely defined positions. As structural data on the resulting metal‐modified DNA are scarce, appropriate model complexes need to be synthesized and structurally characterized. Accordingly, the molecular structures of nine transition metal complexes of N‐methyl‐2, 2'‐dipicolylamine (dipic) are reported. In combination with an azole‐containing artificial nucleoside, this tridentate ligand had recently been used to generate metal‐mediated base pairs (Chem. Commun. 2011 , 47, 11041–11043). The Pd^II and Pt^II complexes reported here confirm that the formation of planar complexes (as required for a metal‐mediated base pair) comprising N‐methyl‐2, 2'‐dipicolylamine is possible. Two Hg^II complexes with differing stoichiometry indicate that a planar structure might also be formed with this metal ion, even though it is not favored. In the complex [Ag₂(dipic)₂](ClO₄)₂, the two Ag^I ions are located close to one another with an Ag ··· Ag distance of 2.9152(3) Å, suggesting the presence of a strong argentophilic interaction.     

Stimuli‐Responsive Polypeptide‐Based Supramolecular Hydrogels Mediated by Ca2+ Ion Cross‐Linking

Hydrogels cross‐linked with metal ions (e.g., Ca²⁺) represent a promising class of bioinspired materials for a wide range of biomedical applications. Herein, we report a facile approach to obtain cross‐linked stimuli‐responsive supramolecular polypeptide hydrogels. The hydrogel is prepared by statistical/block copoly(L‐glutamate)s based copolymers cross‐linked with calcium ions. The incorporation of both oligo(ethylene glycol) (OEG) and glutamic acid residues in the polymer offers thermal‐responsive property and cooperative binding sites with Ca²⁺ ions simultaneously. We present a systematic study of the influence of calcium ions on the gelation behaviors of these copolymers. It is observed that the addition of calcium ions induces the formation of hydrogels. Increasing the concentration of Ca²⁺ ions can significantly enhance the gelation ability of the samples as indicated by increased storage modulus and decreased sol‐to‐gel transition temperature (T_sol‐gel). We further demonstrate that the influence of monomer distribution on the gelation behavior is trivial, which is possibly due to similar morphology of the self‐assemblies. The obtained hydrogels exhibit thermal‐responsive gelation behavior mediated by ion cross‐linking, which enables them to be ideal smart hydrogel system for many applications.     

Poly[[diaquamanganese(II)]‐μ3‐4‐oxido‐2‐oxo‐1,2‐dihydropyrimidine‐5‐carboxylato‐κ4O4,O5:O2:O2]

In the title compound, [Mn(C₅H₂N₂O₄)(H₂O)₂]_n, the Mn^II ion has a distorted octahedral geometry and the 4‐oxido‐2‐oxo‐1,2‐dihydropyrimidine‐5‐carboxylate (Hiso²⁻) anion acts as a μ₃:η⁴‐bridging ligand. Two oxo O atoms from different Hiso²⁻ ligands bridge two Mn^II ions, forming centrosymmetric dinuclear building blocks. Each dinuclear building block interacts with another four by the coordination of the oxide groups and carboxylate O atoms, producing a two‐dimensional framework in the ab plane. Hydrogen bonds further extend the two‐dimensional sheets into a three‐dimensional supramolecular framework.     

A one‐dimensional CdII coordination polymer: catena‐poly[cadmium(II)‐bis(μ‐6‐methylpicolinato)]

In the title compound, [Cd(C₇H₆NO₂)₂]_n, the Cd^II ion has a distorted octahedral geometry. The 6‐methylpyridine‐2‐carboxylate anions are perpendicular to one another and act as bidentate and bridging ligands. Two carboxylate O atoms bridge the Cd^II ions, forming centrosymmetric dinuclear units. These units are further connected via carboxylate O atoms into a one‐dimensional polymeric chain which extends in the [100] direction.     

Molecular dynamics simulation exploration of cooperative migration mechanism of calcium ions in sarcoplasmic reticulum Ca2+‐ATPase

Calcium ATPase is a member of the P‐type ATPase, and it pumps calcium ions from the cytoplasm into the reticulum against a concentration gradient. Several X‐ray structures of different conformations have been solved in recent years, providing basis for elucidating the active transport mechanism of Ca²⁺ ions. In this work, molecular dynamics (MD) simulations were performed at atomic level to investigate the dynamical process of calcium ions moving from the outer mouth of the protein to their binding sites. Five initial locations of Ca²⁺ ions were considered, and the simulations lasted for 2 or 6 ns, respectively. Specific pathways leading to the binding sites and large structural rearrangements around binding sites caused by uptake of calcium ions were identified. A cooperative binding mechanism was observed from our simulation. Firstly, the first Ca²⁺ ion binds to site I , and then, the second Ca²⁺ ion approaches. The interactions between the second Ca²⁺ and the residues around site I disturb the binding state of site I and weaken its binding ability for the first bound Ca²⁺. Because of the electrostatic repulsion of the second Ca²⁺ and the electrostatic attraction of site II , the first bound Ca²⁺ shifts from site I to site II . Concertedly, the second Ca²⁺ binds to site I , forming a binding state with two Ca²⁺ ions, one at site I and the other at site II . Both of Glu908 and Asp800 coordinate with the two Ca²⁺ ions simultaneously during the concerted binding process, which is believed to be the hinge to achieve the concerted binding. In our simulations, four amino acid residues that serve as the channel to link the outer mouth and the binding sites during the binding process were recognized, namely Tyr837, Tyr763, Asn911, and Ser767. The analyses regarding the activity of the proteins via mutations of some key residues also supported our cooperative mechanism. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009     

trans‐(2‐Acetylpyridine‐κ2N,O)dichlorobis(dimethyl sulfoxide‐κS)ruthenium(II)

In the title complex, [RuCl₂(C₇H₇NO)(C₂H₆OS)₂], the metal ion is at the centre of a distorted octahedral NOCl₂S₂ coordination sphere. The neutral 2‐acetyl­pyridine ligand binds to the metal ion through the pyridine N and carbonyl O atoms, forming a five‐membered chelate ring. The monodentate S‐coordinating di­methyl sulfoxide mol­ecules are mutually cis, and the two remaining positions in the coordination sphere are occupied by two mutually trans Cl^? ions.     

Bis(μ‐2‐sulfonatobenzoato)bis[(1,10‐phenanthroline)­lead(II)] dihydrate

In the title centrosymmetric dimer, [Pb₂(sbc)₂(phen)₂]·2H₂O [sbc is the 2‐sulfonatobenzoate dianion (C₇H₄O₅S) and phen is 1,10‐phenanthroline (C₁₂H₈N₂)], each Pb^II ion is six‐coordinated by four O atoms, viz. carboxyl­ate and sulfonate O atoms from two sbc anions, and two N atoms from a 1,10‐phenanthroline ligand. One 1,10‐phenanthroline ligand and the carboxyl­ate group of one sbc ligand are chelated to each Pb^II cation, and the sulfonate group of the other sbc unit is monodentate. One O atom of the chelated carboxyl­ate group also bridges to the other Pb^II cation, so that each pair of Pb^II ions is bridged by two sbc anions and has the same coordination environment, forming a dinuclear ring. Each pair of Pb^II ions is thus connected by two different kinds of bridges, namely a carboxyl­ate short bridge and a carboxyl­ate–sulfonate long bridge. There is also a special position of site symmetry at the centre of the two Pb^II cations.     

Selective separation of strontium by multitopic ion‐pair receptor: A DFT exploration

Selective extraction of a radionuclide in the presence of other interfering ions is one of the vital steps in the back‐end‐of‐the‐nuclear fuel cycle. The presence of interfering cations (such as Ca²⁺) in the radioactive waste and involvement of multiple separation steps are known to be bottlenecks in the efficient Sr²⁺ extraction. Here, using free energy corrected density functional theory, we have proposed a two‐step Sr²⁺ extraction methodology in nitrate media in the presence of interfering Ca²⁺ ion using a multitopic ion‐pair receptor, which was earlier reported to be strongly selective for K⁺ (Kim et al. J. Am. Chem. Soc. 2012, 134 , 1782–1792). To depict the correct free energy trend in the proposed extraction processes, the most probable binding mode of the metal (Sr²⁺, Ca²⁺, and K⁺) nitrates in the host are identified. In excellent agreement with the previously reported experiment, Crown/Pyrrole (C/P) binding is noted to be the most preferable mode for KNO₃, where K⁺ and occupied the Crown (C) and Pyrrole (P) site, respectively. However, the divalent metal ions (Ca²⁺ and Sr²⁺) are noted to marginally prefer Crown/Crown‐Pyrrole (C/CP) mode, in which metal reside at the C site while two nitrates occupy the P site and also simultaneously bind at the outer sphere of C site to coordinate with the metal via monodentate motif. Based on the free energy of extraction, we predict that the selective separation of chemically alike Ca²⁺/Sr²⁺ pair is indeed achievable using this receptor. We propose that once [Sr(NO₃)₂] is extracted in organic media, the receptor's high affinity toward K⁺ in nitrate media can be used to back strip Sr²⁺ to the aqueous phase.     

Study of Six Green Insensitive High Energetic Coordination Polymers Based on Alkali/Alkali‐Earth Metals and 4,5‐Bis(tetrazol‐5‐yl)‐2 H‐1,2,3‐triazole

Constructing insensitive high‐performance energetic coordination polymers (ECPs) with alkali/alkali‐earth metal ions and a nitrogen‐rich organic backbone has been proved to be a feasible strategy in this work. Six diverse dimensional novel ECPs (compounds 1 – 6 ) were successfully synthesized from Na^I, Cs^I, Ca^II, Sr^II, Ba^II ions and a nitrogen‐rich triheterocyclic 4,5‐bis(tetrazol‐5‐yl)‐2 H ‐1,2,3‐triazole (H₃BTT). All compounds show outstanding stability and low sensitivity, the thermal stability of these ECPs are significantly improved as the structural reinforcement increases from 1D to 3D, in which the decomposition temperature of 3D Ba^II based compound 6 is as high as 397 °C. Long‐term storage experiments show that compounds 5 and 6 are stable enough at high temperature. Moreover, the six compounds hold considerable detonation performances, in which Ca^II based compound 5 possesses the detonation velocity of 9.12 km s⁻¹, along with the detonation pressure of 34.51 GPa, exceeding those of most energetic coordination polymers. Burn tests further certify that the six compounds can be versatile pyrotechnics.     

Metal‐Ion‐Mediated Tuning of Duplex DNA Binding by Bis(2‐(2‐pyridyl)‐1H‐benzimidazole)

Studies of double‐stranded‐DNA binding have been performed with three isomeric bis(2‐(n‐pyridyl)‐1H‐benzimidazole)s (n=2, 3, 4). Like the well‐known Hoechst 33258, which is a bisbenzimidazole compound, these three isomers bind to the minor groove of duplex DNA. DNA binding by the three isomers was investigated in the presence of the divalent metal ions Mg²⁺, Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺. Ligand–DNA interactions were probed with fluorescence and circular dichroism spectroscopy. These studies revealed that the binding of the 2‐pyridyl derivative to DNA is dramatically reduced in the presence of Co²⁺, Ni²⁺, and Cu²⁺ ions and is abolished completely at a ligand/metal‐cation ratio of 1:1. Control experiments done with the isomeric 3‐ and 4‐pyridyl derivatives showed that their binding to DNA is unaffected by the aforementioned transition‐metal ions. The ability of 2‐(2‐pyridyl)benzimidazole to chelate metal ions and the conformational changes of the ligand associated with ion chelation probably led to such unusual binding results for the ortho isomer. The addition of ethylenediaminetetraacetic acid (EDTA) reversed the effects completely.     

Design of Ratiometric Fluorescent Probes Based on Arene–Metal‐Ion Interactions and Their Application to CdII and Hydrogen Sulfide Imaging in Living Cells

Non‐coordinative interactions between a metal ion and the aromatic ring of a fluorophore can act as a versatile sensing mechanism for the detection of metal ions with a large emission change of fluorophores. We report the design of fluorescent probes based on arene–metal‐ion interactions and their biological applications. This study found that various probes having different fluorophores and metal binding units displayed significant emission redshift upon complexation with metal ions, such as Ag^I, Cd^II, Hg^II, and Pb^II. X‐ray crystallography of the complexes confirmed that the metal ions were held in close proximity to the fluorophore to form an arene–metal‐ion interaction. Electronic structure calculations based on TDDFT offered a theoretical basis for the sensing mechanism, thus showing that metal ions electrostatically modulate the energy levels of the molecular orbitals of the fluorophore. A fluorescent probe was successfully applied to the ratiometric detection of the uptake of Cd^II ions and hydrogen sulfide (H₂S) in living cells. These results highlight the utility of interactions between arene groups and metal ions in biological analyses.     

Dual‐Modal Magnetic Resonance/Fluorescent Zinc Probes for Pancreatic β‐Cell Mass Imaging

Despite the contribution of changes in pancreatic β‐cell mass to the development of all forms of diabetes mellitus, few robust approaches currently exist to monitor these changes prospectively in vivo. Although magnetic‐resonance imaging (MRI) provides a potentially useful technique, targeting MRI‐active probes to the β cell has proved challenging. Zinc ions are highly concentrated in the secretory granule, but they are relatively less abundant in the exocrine pancreas and in other tissues. We have therefore developed functional dual‐modal probes based on transition‐metal chelates capable of binding zinc. The first of these, Gd ?1 , binds Zn^II directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from λ_em=410 to 500 nm with an increase in relaxivity from r₁=4.2 up to 4.9 mM ^?1 s^?1. The probe is efficiently accumulated into secretory granules in β‐cell‐derived lines and isolated islets, but more poorly by non‐endocrine cells, and leads to a reduction in T₁ in human islets. In vivo murine studies of Gd ?1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes.     

Two mixed‐metal carboxyl­ate–base adducts

The crystal structures of hexa‐μ‐propionato‐1:2κ⁶O:O′;1:3κ⁶O:O′‐di­quinoline‐2κN,3κN‐calcium(II)­dizinc(II), [Ca­Zn₂(C₃H₅O₂)₆(C₉H₇N)₂], and hexa‐μ‐pivalato‐1:2κ⁶O:O′;1:3κ⁶O:O′‐di­quinoline‐2κN,3κN‐calcium(II)­dicobalt(II), [Ca­Co₂(C₅H₉O₂)₆(C₉H₇N)₂], are described. Both contain a linear array of one Ca^II ion and two M^II (M = Zn, Co) ions connected by two sets of three carboxyl­ate ligands in syn–syn bridging modes. The distorted tetrahedral geometry around the M^II ion is completed by a quinoline N atom. The central Ca^II ion occupies a crystallographic inversion centre and is octahedrally coordinated by six carboxyl O atoms in each structure. The Zn^II?Ca^II and Co^II?Ca^II distances are 3.8504 (9) and 3.7929 (5) Å, respectively.     

Selective Coordination of Gallium(III), Zinc(II), and Copper(II) by an Asymmetric Dinucleating Ligand: A Model for Metallophosphatases

Complexation studies of the dinucleating ligand H₃L (H₃L=2‐{[bis(pyridin‐2‐ylmethyl)amino]methyl}‐6‐{[bis(6‐pivaloylamidopyridin‐2‐ylmethyl)amino]methyl}‐4‐methylphenol), with metal‐binding sites A and B, which both provide four donors to a metal ion; a tertiary amine; two pyridines (substituted with amide hydrogen‐bond donors in site B), and a bridging phenolate, with Zn^II, Cu^II, and Ga^III are reported. The titration of H₃L with the three metal ions in solution was monitored by NMR spectroscopy or EPR and UV/Vis/near‐IR spectroscopy, as well as by ESI‐MS to analyze the selectivity of the two metal‐ion sites A and B of this model ligand for metallophosphatases; the spectroscopic assignments are supported by X‐ray crystallography results. The first Zn^II ion coordinates to site A with unsubstituted pyridine donors and, upon addition of a second equivalent of Zn^II, this coordinates to the sterically less accessible site B. From a similar titration with Ga^III, it emerges that only a mononuclear complex is obtained, with the Ga^III center coordinated to site A. When one equivalent of Ga^III is reacted with the mononuclear Zn^II complex, Zn^II is forced by Ga^III to exchange the site; this results in a dinuclear complex with Ga^III in site A and Zn^II in site B. With Cu^II, two isomers are observed: one with and the other without a bridging phenolate; these differ significantly in their spectroscopic and magnetic properties.     

Construction of Insulin 18‐mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites

Controlled self‐assembly (SA) of proteins offers the possibility to tune their properties or to create new materials. Herein, we present the synthesis of a modified human insulin (HI) with two distinct metal‐ion binding sites, one native, the other abiotic, enabling hierarchical SA through coordination with two different metal ions. Selective attachment of an abiotic 2,2′‐bipyridine (bipy) ligand to HI, yielding HI–bipy, enabled Zn^II‐binding hexamers to SA into trimers of hexamers, [[HI–bipy]₆]₃, driven by octahedral coordination to a Fe^II ion. The structures were studied in solution by small‐angle X‐ray scattering and on surfaces with AFM. The abiotic metal ligand had a higher affinity for Fe^II than Zn^II ions, enabling control of the hexamer formation with Zn^II and the formation of trimers of hexamers with Fe^II ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine.     

Coordination Chemistry of N‐Heterocyclic Nitrenium‐Based Ligands

Comprehensive studies on the coordination properties of tridentate nitrenium‐based ligands are presented. N‐heterocyclic nitrenium ions demonstrate general and versatile binding abilities to various transition metals, as exemplified by the synthesis and characterization of Rh^I, Rh^III, Mo⁰, Ru⁰, Ru^II, Pd^II, Pt^II, Pt^IV, and Ag^I complexes based on these unusual ligands. Formation of nitrenium–metal bonds is unambiguously confirmed both in solution by selective ¹⁵N‐labeling experiments and in the solid state by X‐ray crystallography. The generality of N‐heterocyclic nitrenium as a ligand is also validated by a systematic DFT study of its affinity towards all second‐row transition and post‐transition metals (Y–Cd) in terms of the corresponding bond‐dissociation energies.     

Copper(II) and Sodium(I) Complexes based on 3,7‐Diacetyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane‐5‐oxide: Synthesis,Characterization, and Catalytic Activity

The reaction of 3,7‐diacetyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane (DAPTA) with metal salts of Cu^II or Na^I/Ni^II under mild conditions led to the oxidized phosphane derivative 3,7‐diacetyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane‐5‐oxide (DAPTA=O) and to the first examples of metal complexes based on the DAPTA=O ligand, that is, [Cu^II(μ‐CH₃COO)₂(κO‐DAPTA=O)]₂ ( 1 ) and [Na(1κOO′;2κO‐DAPTA=O)(MeOH)]₂(BPh₄)₂ ( 2 ). The catalytic activity of 1 was tested in the Henry reaction and for the aerobic 2,2,6,6‐tetramethylpiperidin‐1‐oxyl (TEMPO)‐mediated oxidation of benzyl alcohol. Compound 1 was also evaluated as a model system for the catechol oxidase enzyme by using 3,5‐di‐tert‐butylcatechol as the substrate. The kinetic data fitted the Michaelis–Menten equation and enabled the obtainment of a rate constant for the catalytic reaction; this rate constant is among the highest obtained for this substrate with the use of dinuclear Cu^II complexes. DFT calculations discarded a bridging mode binding type of the substrate and suggested a mixed‐valence Cu^II/Cu^I complex intermediate, in which the spin electron density is mostly concentrated at one of the Cu atoms and at the organic ligand.     

Formation and Dynamic Behavior of Mono‐ and Bimetallic Cadmium(II) Porphyrin Complexes: Allosteric Control of Coupled Intraligand Metal Migrations

The complexation behavior of a bis‐strapped porphyrin ligand ( 1 ) towards Cd^II has been investigated by ¹H and ¹¹³Cd NMR spectroscopy with the help of X‐ray diffraction structures. The presence of an overhanging carboxylic acid group on each side of the macrocycle is responsible for the instantaneous insertion of the metal ion(s) at room temperature, and allows the formation of bimetallic species with unusual coordination modes at the origin of unique dynamic behaviors. In the absence of base, a C₂‐symmetric bimetallic complex ( 1Cd₂ ) is readily formed, in which the porphyrin acts as a bridging ligand. Both Cd^II ions are bound to the N core and to a COO^? group of a strap. In contrast, the presence of a base induces a two‐step binding process with the successive formation of mono and bimetallic species ( 1^Cd and 1_Cd?CdOAc ). Formally, a Cd^II ion is first inserted into the N core and experiences a strong out‐of‐plane (OOP) displacement due to the binding of an overhanging carbonyl group in an apical position. A second Cd^II ion then binds exclusively to the strap on the opposite side, in a so‐called hanging‐atop (HAT) coordination mode. These two complexes display a fluxional behavior that relies on intraligand migration processes of the metal ion(s). In 1^Cd , the Cd^II ion exchanges between the two equivalent overhanging apical ligands by funneling through the porphyrin ring. In 1_Cd?CdOAc , the two Cd^II ions exchange their coordination mode (HAT?OOP) in a concerted way while staying on their respective side of the macrocycle, in a so‐called Newton’s cradle‐like motion. The intramolecular pathway was notably evidenced by variable temperature ¹¹³Cd heteronuclear NMR experiments. This coupled motion of the Cd^II cations is under allosteric control; the addition of an acetate anion (the allosteric effector) to the “resting” C₂‐symmetric complex 1Cd₂ affords the dissymmetric complex 1_Cd?CdOAc and triggers equilibrium between its two degenerate states. The rate of the swinging motion further depends on the concentration of AcO^?, with a higher concentration leading to a slower motion. As compared with the related Pb^II and Bi^III bimetallic complexes, the Newton’s cradle‐like motion proceeds faster with the smaller Cd^II ion. These results open the way to novel multistable devices and switches.