Functional Mimics Research Articles

Probing the electronic and mechanistic roles of the μ4-sulfur atom in a synthetic CuZ model system.

Nitrous oxide (N2O) contributes significantly to ozone layer depletion and is a potent greenhouse agent, motivating interest in the chemical details of biological N2O fixation by nitrous oxide reductase (N2OR) during bacterial denitrification. In this study, we report a combined experimental/computational study of a synthetic [4Cu:1S] cluster supported by N-donor ligands that can be considered the closest structural and functional mimic of the CuZ catalytic site in N2OR reported to date. Quantitative N2 measurements during synthetic N2O reduction were used to determine reaction stoichiometry, which in turn was used as the basis for density functional theory (DFT) modeling of hypothetical reaction intermediates. The mechanism for N2O reduction emerging from this computational modeling involves cooperative activation of N2O across a Cu/S cluster edge. Direct interaction of the μ4-S ligand with the N2O substrate during coordination and N–O bond cleavage represents an unconventional mechanistic paradigm to be considered for the chemistry of CuZ and related metal–sulfur clusters. Consistent with hypothetical participation of the μ4-S unit in two-electron reduction of N2O, Cu K-edge and S K-edge X-ray absorption spectroscopy (XAS) reveal a high degree of participation by the μ4-S in redox changes, with approximately 21% S 3p contribution to the redox-active molecular orbital in the highly covalent [4Cu:1S] core, compared to approximately 14% Cu 3d contribution per copper. The XAS data included in this study represent the first spectroscopic interrogation of multiple redox levels of a [4Cu:1S] cluster and show high fidelity to the biological CuZ site.

BiAb Mediated Restoration of the Linkage between Dystroglycan and Laminin-211 as a Therapeutic Approach for α-Dystroglycanopathies.

Patients with α-dystroglycanopathies, a subgroup of rare congenital muscular dystrophies, present with a spectrum of clinical manifestations that includes muscular dystrophy as well as CNS and ocular abnormalities. Although patients with α-dystroglycanopathies are genetically heterogeneous, they share a common defect of aberrant post-translational glycosylation modification of the dystroglycan alpha-subunit, which renders it defective in binding to several extracellular ligands such as laminin-211 in skeletal muscles, agrin in neuromuscular junctions, neurexin in the CNS, and pikachurin in the eye, leading to various symptoms. The genetic heterogeneity associated with the development of α-dystroglycanopathies poses significant challenges to developing a generalized treatment to address the spectrum of genetic defects. Here, we propose the development of a bispecific antibody (biAb) that functions as a surrogate molecular linker to reconnect laminin-211 and the dystroglycan beta-subunit to ameliorate sarcolemmal fragility, a primary pathology in patients with α-dystroglycan-related muscular dystrophies. We show that the treatment of LARGEmyd-3J mice, an α-dystroglycanopathy model, with the biAb improved muscle function and protected muscles from exercise-induced damage. These results demonstrate the viability of a biAb that binds to laminin-211 and dystroglycan simultaneously as a potential treatment for patients with α-dystroglycanopathy.

Rational De Novo Design of a Cu Metalloenzyme for Superoxide Dismutation.

Superoxide dismutases (SODs) are highly efficient enzymes for superoxide dismutation and the first line of defense against oxidative stress. These metalloproteins contain a redox-active metal ion in their active site (Mn, Cu, Fe, Ni) with a tightly controlled reduction potential found in a close range around the optimal value of 0.36 V versus the normal hydrogen electrode (NHE). Rationally designed proteins with well-defined three-dimensional structures offer new opportunities for obtaining functional SOD mimics. Here, we explore four different copper-binding scaffolds: H3 (His3 ), H4 (His4 ), H2 DH (His3 Asp with two His and one Asp in the same plane) and H3 D (His3 Asp with three His in the same plane) by using the scaffold of the de novo protein GRα3 D. EPR and XAS analysis of the resulting copper complexes demonstrates that they are good CuII -bound structural mimics of Cu-only SODs. Furthermore, all the complexes exhibit SOD activity, though three orders of magnitude slower than the native enzyme, making them the first de novo copper SOD mimics.

The Oncogenic Kaposi’s Sarcoma-Associated Herpesvirus Encodes a Mimic of the Tumor-Suppressive miR-15/16 miRNA Family

SUMMARYMany tumor viruses encode oncogenes of cellular origin. Here, we report an oncoviral mimic of a cellular tumor suppressor. The Kaposi’s sarcoma-associated herpesvirus (KSHV) microRNA (miRNA) miR-K6-5p shares sequence similarity to the tumor-suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 family miRNA targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells confers a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of miR-15/16 family miRNAs. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is an unusual example of an oncogenic virus that encodes a viral mimic of a cellular tumor suppressor. Encoding a tumor-suppressive miRNA could help KSHV balance viral oncogene expression and thereby avoid severe pathogenesis in the healthy host.

Production of functional mimics of human milk oligosaccharides by enzymatic glycosylation of bovine milk oligosaccharides

Consumption of mothers' milk is associated with reduced incidence and severity of enteric infections, leading to reduced morbidity in breastfed infants. Fucosylated and sialylated human milk oligosaccharides (HMO) are important for both direct antimicrobial action – likely via a decoy effect – and indirect antimicrobial action through commensal growth enhancement. Bovine milk oligosaccharides (BMO) are a potential source of HMO-mimics as BMO resemble HMO; however, they have simpler and less fucosylated structures. BMO isolated at large scales from bovine whey permeate were modified by the addition of fucose and/or sialic acid to generate HMO-like glycans using high-yield and cost-effective one-pot multienzyme approaches. Quadrupole time-of-flight LC/MS analysis revealed that 22 oligosaccharides were synthesized and 9 had identical composition to known HMO. Preliminary anti-adherence activity assays indicated that fucosylated BMO decreased the uptake of enterohemorrhagic Escherichia coli O157:H7 by human intestinal epithelial Caco-2 cells more effectively than native BMO.

Epidemiology of functional stroke mimic patients: a systematic review and meta-analysis.

Stroke mimics form a significant proportion of cases in acute stroke services and some present with functional neurological disorder. Little is known about the prevalence or clinical characteristics of functional stroke mimics (FSMs). A systematic literature search and meta-analysis were carried out on published studies reporting suspected stroke and stroke mimic rates; 114 papers met the inclusion criteria of which 70 provided an FSM rate. Random-effects models estimated prevalence rates across settings and moderators of FSM rate. Pooled proportions indicated that 25% [95% confidence intervals (CI), 22-27%] of suspected stroke cases were stroke mimics. Within the 67 studies providing positive FSM rates, FSMs represented 15% (95% CI, 13-18%) of stroke mimics and 2% (95% CI, 2-3%) of suspected strokes. FSMs were younger and more likely to be female, and presented more with weakness/numbness but less with reduced consciousness or language problems. Stratified analyses suggested higher stroke mimic rates in primary care versus acute settings (38% vs. 12%) but higher FSM rates in stroke units compared with primary care (24% vs. 12%). Functional rates were higher in studies that were descriptive, retrospective and in patients receiving thrombolysis. Several studies reported the proportion of functional stroke patients presenting to stroke services. FSMs have discernible demographic and clinical characteristics, but there is a conspicuous lack of evidence on their presentation or guidance for treatment. The social and psychological mechanisms underlying FSM presentations need more accurate quantification to help inform stroke pathways and improve care for these patients.

Zinc(II) complexes of a versatile heptadentate ligand as phosphohydrolase structural and functional mimics

A mono-nuclear [Zn(H2O)6][1] and a di-nuclear zinc (NMe4)2[2] complexes of a carboxylate-rich ligand, N,N′-Bis[2-carboxybenzomethyl]-N,N′ -Bis[carboxymethyl]-1,3-diaminopropan-2-ol (H5ccdp) have shown catalytic activity towards hydrolysis of the phosphoester bonds in bis(4-nitrophenyl) phenylphosphonate, BNPPP. Kinetic measurements for the zinc(II) complexes, using spectrophotometric techniques in DMSO, were performed in order to investigate the metal-metal cooperativity vs metal-hydrogen bonding effect on the phosphoester bond cleavage rate in BNPP. The results showed that, compared to un-catalyzed hydrolysis of BNPPP, (NMe4)2[2] complex showed 103-fold rate enhancement, whereas ([Zn(H2O)6][1]) shows only 450-fold rate enhancement under the same reaction conditions. Based on the structural and activity information obtained in this study, reaction mechanisms for the hydrolysis of BNPPP have been proposed.

Design and synthesis of glycomimetics: Recent advances.

In the past few decades, our understanding of glycan information-encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein-targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

The influence of the tertiary butyl group in the ligand frame on the catalytic activities, DNA cleavage ability and cytotoxicity of dinuclear nickel(II) complexes

Dinuclear phenoxo-bridged nickel complexes [Ni2(L1)H2O(CH3COO)](1) and [Ni2(L2)H2O(CH3COO)](2) (where L1H3° = 2-(2′-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabutenyl]-3-enyl]-1,3-imidazolidine and L2H3° = 2-(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-bis[4-(3,5-di-tert-butyl-2-hydroxyphenyl)-3-azabutenyl]-1,3-idazolidine, and H stands for dissociable protons) have been synthesized and characterized by different spectroscopic methods. Molecular structure of 2 was determined by X-ray crystallography. Redox properties of complexes 1 and 2 were investigated by cyclic voltammetric studies. As functional mimic of active site of galactose oxidase enzyme, complexes 1 and 2 were utilized for the oxidation of primary alcohol. Both the complexes exhibited catecholase activity. DNA interaction studies on complexes 1 and 2 were also investigated. Self-activated DNA cleavage activity of complex 2 was observed. The cytotoxicity of the complexes 1 and 2 was measured using a standard MTT assay and IC50 values for of 1 and 2 were found to be 21.92 µM and 20.69 µM on MCF-7 breast cancer cell line respectively.

Supramolecular Assembly of High-Density Lipoprotein Mimetic Nanoparticles Using Lipid-Conjugated Core Scaffolds.

Synthetic high-density lipoprotein (HDL) mimics have emerged as promising therapeutic agents. However, approaches to date have been unable to reproduce key features of spherical HDLs, which are the most abundant human HDL species. Here, we report the synthesis and characterization of spherical HDL mimics using lipid-conjugated organic core scaffolds. The core design motif constrains and orients phospholipid geometry to facilitate the assembly of soft-core nanoparticles that are approximately 10 nm in diameter and resemble human HDLs in their size, shape, surface chemistry, composition, and protein secondary structure. These particles execute salient HDL functions, including efflux of cholesterol from macrophages, cholesterol delivery to hepatocytes, support lecithin:cholesterol acyltransferase activity, and suppress inflammation. These results represent a significant step toward a genuine functional mimic of human HDLs.

Functional stroke mimics: cultural differences and challenges to rising healthcare costs

Functional neurological disorders mimicking stroke are described in literature from across the globe (1-4). Stroke mimics account for a significant proportion of acute stroke evaluations in emergency rooms among which functional stroke mimics (FSMs) are seen in a substantial proportion. These disorders present a diagnostic challenge as acute stroke management calls for administration of potentially high-risk therapies in a time sensitive manner.

Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity

ObjectiveInfection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors. microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene...

Ternary complexes containing Copper(II), l-Valinate and α, ά-bipyridyl or 1,10-phenanthroline: Synthesis, characterization, ligand substitution and oxidase biomimetic catalytic activity studies

Ternary copper(II) complexes with the molecular formulae of [CuIILL′]X or [CuIILL′X]; L = l-Valinate; L′ = α, ά-bipyridyl or 1,10 - phenanthroline and X is Cl¯, Br¯, NO3¯, AcO¯, ½SO42− or ClO4¯ were synthesized. Elemental and thermal analysis in addition to electrochemical (molar conductance and cyclic voltammetry), magnetic moment measurements as well spectral (FT-IR, UV–Vis and ESR) techniques were used to characterize the complexes. The spectroscopic results suggested square pyramidal and square planar geometries for the five- and four-coordinate complexes respectively. Powder X-ray diffraction spectral data along with the structure solution program Expo 2014 has been used for structural elucidation of the sulfato complexes 1 and 5. Stopped follow technique was employed to study the substitution of the nonelectrolytic coordinately counter anion ligand by using thiourea (TU) as a function of nucleophile and a biphasic process is proposed. An initial fast reaction is followed by a slower one and the initial one was found to be counter ion dependent. Bio-mimicking the multicopper oxidase enzyme such as catechol oxidase and phenoxazinone synthase is a further goal of the present study. Catalytic examinations displayed that the present complexes are promising candidates as functional mimic of the examined enzymes and the probable mechanistic catalytic sequences are discussed.

Diversity and abundance of Lepidoptera and Coleoptera in multiple-species reforestation plantings to offset emissions of carbon dioxide

ABSTRACT Multiple-species (floristically diverse) plantings of trees and shrubs in former agricultural landscapes to offset (sequester) emissions of carbon dioxide are a recent component of Australian landscapes. Although their potential to mitigate biodiversity loss is recognised, this ecological function has not been investigated, in particular with respect to insect diversity. Over two summers, we used light trapping to sample Lepidoptera (moths) and Coleoptera (beetles) in multiple-species plantings in two distinct locations in Victoria (plantings of four ages per location) as well as in nearby remnant forest and in pasture. At both locations, we found that plantings had a greater abundance of Lepidoptera than remnants but that the abundance in plantings was comparable to the abundance in pasture. The species richness of Lepidoptera in plantings did not differ significantly from that in remnants but was significantly greater than that in pasture. The abundance and species richness of Coleoptera in plantings was lower than in remnant forests but higher than in pasture. The community composition of Lepidoptera and Coleoptera in plantings was intermediate between that of remnant forest and pasture, i.e. possibly transitional between the two vegetation types. Dissimilarity between all vegetation types was nevertheless high, reflecting that the abundance of individual taxa reflects the influence of temporally and spatially dependent factors, e.g. host plant size and suitability. Greater abundances of grass-feeding Lepidoptera in plantings explained much of the dissimilarity between plantings and remnant forests. Proximity to remnant forest was an important determinant of the community composition of Lepidoptera but not of Coleoptera. Moth forewing length (relevant to vagility which is an indicator of dispersal capacity) appeared less important to proximity relationships than larval host plant specificity, i.e. whether grass or dicot-feeding. The location of sequestration plantings relative to remnant forest as well as their composition (including the persistence of pasture grasses) will determine the attractiveness of the resources provided to insect herbivores and hence the rate at which they are colonised. Plantings near remnant native forest benefit insect diversity but adoption of novel silvicultural practices could hasten the rate at which they become functional mimics of native forests and support more comparable communities of insect. Potential trade-offs between increased establishment costs and more complex carbon accounting might need to be investigated to cost biodiversity credits associated with dual accreditation schemes.

LncRNA/circRNA–miRNA–mRNA networks regulate the development of root and shoot meristems of Populus

Root and shoot meristems play essential roles in the formation and development of plant tissues and organs. However, little is known about the roles of non-coding RNAs (ncRNAs) in the regulation of maintenance and differentiation of root and shoot meristems in Populus. Here, we first identified and characterized many microRNAs (miRNAs), mRNAs, long ncRNAs (lncRNAs) and circular RNAs (circRNAs) from the root tip and shoot tip of poplar at the genome-wide level. A total of 73,012 mRNAs, 13,099 lncRNAs, 47 circRNAs, and 114 miRNAs were identified by strand-specific RNA sequencing and small RNA sequencing. Differential expression analysis revealed that there were 8501 differentially expressed (DE) mRNAs, 295 DE lncRNAs, 15 DE circRNAs and 45 DE miRNAs, and their functions were annotated. Some lncRNAs and circRNAs have miRNA binding sites, and these ncRNAs may act as functional endogenous pseudo target mimics. Therefore, we constructed lncRNA − peu-miR394a-5p − mRNA, lncRNA − peu-miR166a − mRNA, lncRNA/circRNA − peu-miR396a − mRNA and lncRNA/circRNA − peu-miR160a − PeARF regulatory networks and verified the target genes of these four miRNAs by degradome sequencing. Furthermore, by overexpressing pei-miR160a, we found that pei-miR160a negatively regulated the expression of six PeARFs, five lncRNAs and one circRNA. Our findings provide new insights into the lncRNA/circRNA − miRNA − mRNA networks involved in the development of the root and shoot meristems of Populus.

Aluminum Hydroxide Secondary Building Units in a Metal–Organic Framework Support Earth-Abundant Metal Catalysts for Broad-Scope Organic Transformations

The intrinsic heterogeneity of alumina (Al2O3) surface presents a challenge for the development of alumina-supported single-site heterogeneous catalysts and hinders the characterization of catalytic species at the molecular level as well as the elucidation of mechanistic details of the catalytic reactions. Here we report the use of aluminum hydroxide secondary building units (SBUs) in the MIL-53(Al) metal–organic framework (MOF) with the formula Al(μ2–OH)(BDC) (BDC = 1,4-benzenedicarboxylate) as a uniform and structurally defined functional mimic of Al2O3 surface for supporting Earth-abundant metal (EAM) catalysts. The μ2–OH groups in MIL-53(Al) SBUs were readily deprotonated and metalated with CoCl2 and FeCl2 to afford MIL-53(Al)-CoCl and MIL-53(Al)-FeCl precatalysts which were characterized by powder X-ray diffraction, nitrogen sorption, elemental analysis, density functional theory, and extended X-ray fine structure spectroscopy. Activation with NaBEt3H converted MIL-53(Al)-CoCl to MIL-53(Al)-CoH which effectively catalyzed hydroboration of alkynes and nitriles and hydrosilylation of esters. X-ray photoelectron spectroscopy and X-ray absorption near-edge spectroscopy (XANES) indicated the presence of AlIII and CoII centers in MIL-53(Al)-CoH while deuterium labeling studies suggested σ-bond metathesis as a key step for the MIL-53(Al)-CoH-catalyzed addition reactions. MIL-53(Al)-FeCl competently catalyzed oxidative Csp3–H amination and Wacker-type alkene oxidation. XANES analysis revealed the oxidation of FeII to FeIII centers in the activated MIL-53(Al)-FeCl catalyst and suggested that oxidative Csp3–H amination occurs via the formation of FeIII–OtBu species by single electron transfer between FeII centers in MIL-53(Al)-FeCl and (tBuO)2 with concomitant generation of 1 equiv of tBuO· radical, C–H activation through hydrogen atom abstraction to generate alkyl radicals, protonation of FeIII–OtBu by aniline to generate MIL-53(Al)-FeIII-anilide, and finally C–N coupling between the FeIII-anilide and alkyl radical to form the Csp3–H amination product and regenerate the FeII catalyst. These highly active single-site MOF-based solid catalysts were readily recovered and reused up to five times without significant decrease in catalytic activity. This work thus demonstrates the great potential of using the aluminum hydroxide SBUs in MOFs to support EAM catalysts for important organic transformations.

Biomorphic Engineering of Multifunctional Polylactide Stomatocytes toward Therapeutic Nano-Red Blood Cells.

Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)‐block‐poly(D,L‐lactide), possess an oblate‐like morphology reminiscent of RBCs. This unique dual‐compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen‐binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano‐RBCs have long circulation times in mice, with the membrane‐coated ones outperforming the uncoated stomatoctyes. The capacity of nano‐RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer‐induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.

DNA aptamer assemblies as fibroblast growth factor mimics and their application in stem cell culture.

Replacing expensive and thermally unstable growth factors with synthetic alternatives has been an important issue in stem cell-based regenerative medicines. Here we developed DNA aptamer-assemblies that act as functional mimics of basic fibroblast growth factor (bFGF), one of the essential factors for stem cell culture. The most potent aptamer assembly named TD0, composed solely of 76-mer single-stranded DNA, could support the self-renewal and pluripotency of induced pluripotent stem cells (iPSCs). This work presents the first application of DNA aptamer in the maintenance of iPSCs.

Enrichment of S-Palmitoylated Proteins for Mass Spectrometry Analysis.

As the 10-year anniversary of their first introduction approaches, alkynyl fatty acids have revolutionized the analysis of S-palmitoylation dynamics, acting as functional mimics incorporated into native modification sites in cultured cells. The alkyne functional group provides a robust handle for bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) to reporter-linked azides, forming a stable conjugate for enrichment for mass spectrometry analysis or in-gel fluorescence. Importantly, metabolic labeling enables time-dependent analysis of S-palmitoylation dynamics, which can be used to profile incorporation and turnover rates across the proteome. Here we present a protocol for cell labeling, click chemistry conjugation, enrichment, and isobaric tandem mass tag labeling for quantitative mass spectrometry analysis of protein S-palmitoylation.

Biomimetic Cu, Zn and Cu2 complexes inserted in mesoporous silica as catalysts for superoxide dismutation

Abstract Three CuZn-superoxide dismutase (SOD) functional mimics, [CuZn(dien)2(μ-Im)](ClO4)3 (1), [Cu2(dien)2(μ-Im)](ClO4)3 (2) (Im = imidazole, dien = diethylenetriamine), and [CuZn(salpn)Cl2] (3) (H2salpn = 1,3-bis(salicylideneamino)propane), were successfully inserted into the nanochannels of SBA-15 type mesoporous silica with retention of the silica mesostructure. X-ray absorption spectroscopic studies indicate that the encapsulated complexes keep unchanged the first-shell environment of Cu(II) and Zn(II) ions. Magnetic measurements suggest that the nanochannels constrain the geometry of the μ-imidazolate-Cu(II)2 core modifying the relative orientation of the two copper coordination planes. Confinement imposed by the silica nanochannels upon encapsulation of complexes 1 and 2 leads to stable hybrid materials at physiological pH with enhanced SOD activity relative to the free complexes. Unlike the imidazolato-bridged compounds, insertion of 3 in mesoporous silica leads to a less stable hybrid material exhibiting partial release into the aqueous solution and O2•− dismutation rate slower than the free complex. The covalent binding of a mononuclear Cu(dien)Im+ moiety to the mesoporous silica showed lower SOD activity than encapsulated imidazolato-bridged CuZn and Cu2 complexes. The results emphasize the positive effect of encapsulation on SOD activity of imidazolato-bridged dinuclear complexes.