Zinc Coordination Research Articles

In vivo functional significance of direct physical interaction between period and cryptochrome in mammalian circadian rhythm generation

Abstract In the current model, the auto-negative feedback action of Period (Per) and Cryptochrome (Cry) on their own transcription is the hallmark mechanism driving cell-autonomous circadian rhythms. Although this model likely makes sense even if Per and Cry undertake this action in a mutually independent manner, many studies have suggested the functional significance of direct physical interaction between Per and Cry. However, even though the interaction is a biochemical process that pertains to the fundamentals of the circadian oscillator, its in vivo contribution to circadian rhythm generation remains undefined. To answer this question, we focused on zinc coordination between Per and Cry, whose contribution to circadian rhythm generation remains undefined. Specifically, we aimed to impair endogenous Per-Cry association by introducing an amino acid substitution to zinc-coordinating residues located at the Per1 and Per2 C-terminal facing Cry in mice. These mice did not show severe impairment in the Per-Cry physical interaction, but rather a shortened period and decreased robustness in circadian rhythms at the tissue-autonomous and whole-body levels. Furthermore, these mice also showed a decreased in Per half-life, suggesting that impaired fine-tuning of Per half-life caused abnormal circadian period and robustness in vivo. We also found a minor but significant impact of a reindeer-specific Per2 mutation located in the Per-Cry interface on circadian rhythms in vivo. These lines of evidence indicate that only partial impairment of the Per-Cry physical interaction produces a substantial effect on circadian period and robustness, supporting the in vivo functional significance of the interaction.

Solvent and additive-controlled supramolecular isomerism in zinc coordination polymers.

A new series of Zn(II) supramolecular isomers containing ditopic 1,3-di(pyridin-4-yl)urea (4bpu) ligand were synthesized and characterized by infrared analysis, elemental analysis and TGA as well as single-crystal X-ray diffraction analysis. Four solvent-induced pseudopolymorphic zinc (II) coordination polymers (CPs), namely, {[Zn(4bpu)(OAc)2](CH3OH)}n (1), {[Zn(4bpu)(OAc)2](C2H5OH)}n (2), {[Zn(4bpu)(OAc)2](HOCH2CH2OH)}n (3), and {[Zn(4bpu)(OAc)2](0.5H2O)}n (4), were prepared by the reaction of Zn(OAc)2.2H2O and 4bpu via self-assembly under varying solvent systems. Also, a pair of polymorphic coordination polymers namely, {[Zn(4bpu)(OAc)2](CH3OH)}n (1α) and {[Zn3(4bpu)3(OAc)6](CH3OH)2}n(1β), was prepared in the presence of different organic additives. Single-crystal X-ray diffraction confirmed that 1-4 and 1α display 1D polymeric zig-zag chains and 1β exhibits 1D triple-stranded ladders that were self-assembled through various supramolecular interactions. In addition, a series of dissolution-recrystallization structural transformations (DRST) were performed on these supramolecular isomers.

Coordination-driven molecular switch on the base of an ESIPT-capable pyrimidine ligand: Synthesis, fine-tuning of emission by the halide anion and theoretical studies

ESIPT-based materials (ESIPT = Excited State Intramolecular Proton Transfer) find diverse applications in optoelectronics and biomedicine owing to the peculiarities of their luminescence properties. Here, an ESIPT-capable compound 2-(3,5-dimethyl-1H-pyrazol-1-yl)-4-(2-hydroxyphenyl)pyrimidine (HL4,2,Me) featuring a short O–H⋅⋅⋅N intramolecular hydrogen bond and two N,N-sites for metal binding has been synthesized. HL4,2,Me is the first reported molecule which can act as an ESIPT molecular switch triggered by metal ion coordination without its deprotonation. Drastic changes in the HL4,2,Me conformation in the [Zn(HL4,2,Me)X2] (X = Cl, Br,I) complexes significantly alter the photoluminescence response compared to the free ligand. In the solid state, HL4,2,Me exhibits barrierless ESIPT and large Stokes-shifted yellow-orange emission due to the interplay of anti-Kasha S2 → S0 fluorescence and Kasha-like T1 → S0 phosphorescence radiative channels. The violation of Kasha’s rule for HL4,2,Me is justified by an extraordinarily large S2 – S1 energy gap (ca. 0.9 eV), slowing down the rate of S2 → S1 internal conversion. The photoluminescence behavior of the ESIPT–incapable zinc(II) coordination compounds strongly depends on the halide anion: the chlorido complex exhibits only fluorescence, the bromido complex displays a minor phosphorescence channel in addition to a major fluorescence channel, while the iodido complex exhibits predominantly phosphorescence. As a result, the emission color of the [Zn(HL4,2,Me)X2] complexes changes gradually from blue for X = Cl to orange for X = I, providing a platform for the fine-tuning of emission by the halide anion.

Synthesis, crystal Structure, and luminescence of zinc coordination polymers with a new Fuctionalized terpyridyl Sulfonate ligand

Four Zinc(II) coordination polymers based on a new ligand with terpyridyl and benzenesulfonyl groups, namely, [Zn1.5(STP)2Cl]n·1.5nH2O (1), [Zn(STP)(1,4- bdc)0.5]n·0.5nH2O(2), [Zn(STP-O)]n·0.5nH2O (3), [Zn(STP-OH)(1,4- bdc)0.5]n·0.5nH2O (4), (HSTP = 2-(4,2’:6’,4″-terpyridine-4’-yl)benzenesulfonic acid) have been synthesized under hydrothermal and characterized by elemental analysis, IR, PXRD and single crystal X-ray diffraction. Compound 1 exhibits an interpenetrating 3D network. Compound 2 displays a (3,4)-connected Ins topological network. Compound 3 shows a (3,6)-connected 3D rtl network. Compound 4 reveals a (3,4)-connected Ins topological network. The structural diversities well confirm the rich coordination chemistry of HSTP. The photoluminescence for 1–2 and thermal stabilities of 1–4 were also studies. Additionally, a brief analysis for hydroxylation of terpyridine group during hydrothermal reaction was carried out.

Harnessing Novel Zinc(II) Coordination Complex for Green Synthesis of ZnO Nanoparticles Boasting Remarkable Photocatalytic Degradation and Targeted Detection of Cr(VI) and Hg(II) Ions

Harnessing Novel Zinc(II) Coordination Complex for Green Synthesis of ZnO Nanoparticles Boasting Remarkable Photocatalytic Degradation and Targeted Detection of Cr(VI) and Hg(II) Ions

Earlier endosomal escape improves the catalytic activity of delivered enzyme cargo.

AbstractThere is enormous interest in strategies to efficiently traffic biologics–proteins, nucleic acids, and complexes thereof–into the mammalian cell cytosol and internal organelles. Not only must these materials reach the appropriate cellular locale fully intact and in therapeutically relevant concentrations, they must also retain activity upon arrival. The question of residual activity is especially critical when delivery involves exposure to the late endocytic pathway, whose acidic lumenal environment can denature and/or degrade internalized material. ZF5.3 is a compact, stable, rationally designed mini-protein that efficiently escapes intact from late endocytic vesicles, with or without covalently linked protein cargo. Here, using insights from mechanistic studies on the pathway of endosomal escape and classic knowledge regarding the bioinorganic chemistry of zinc(II) coordination in small proteins, we re-designed the sequence of ZF5.3 to successfully alter the timing (but not the efficiency) of endosomal escape. The new mini-protein we describe, AV5.3, escapes earlier than ZF5.3 along the endocytic pathway with no loss in efficiency, with or without enzyme cargo. More importantly, earlier endosomal escape translates into higher enzymatic activity upon arrival in the cytosol. Delivery of the pH-sensitive protein dihydrofolate reductase (DHFR) with AV5.3 results in substantial catalytic activity in the cytosol, whereas delivery with ZF5.3 does not. The activity of AV5.3-DHFR upon delivery is sufficient to rescue a genetic DHFR deletion in CHO cells. This work provides evidence that programmed trafficking through the endosomal pathway is a viable strategy for the efficient cytosolic delivery of therapeutic proteins.Abstract Figure

Structure of Metiram, a Crystalline Zinc Coordination Complex with Amorphous Side Phase

Structure of Metiram, a Crystalline Zinc Coordination Complex with Amorphous Side Phase

Synthesis, structures, and photoluminescence of zinc(II) coordination polymers based on carboxylates and the semirigid ligand 1,4-bis(2-methylbenzimidazol-1-ylmethyl)benzene

Two fluorescent Zn(II) polymers (1 and 2) with different dicarboxylic acid co-ligands have been obtained under hydrothermal reaction conditions. In 1 and 2, the flexible bmb adopts two trans-conformations with different Ndonor···N–Csp3···Csp3 torsion angles, generating 3-D interspersed (412·63)-pcu grids. The dicarboxylic acid co-ligands influence the conformation of bmb, which lead to diverse spatial structures from a single helix to a 2-D lattice network. Photoluminescence investigations reveal that 1 has a redshift compared with o-H2oba (4,4'-oxydibenzoic acid) and 2 has a blueshift of 20 nm compared with H2bpdc ([1,1'-biphenyl]-4,4'-dicarboxylic acid), which can be attributed to a ligand-centered charge transfer.

Zinc Coordination Lipid Nanoparticles Co-Delivering Calcium Peroxide and Chelating STING agonist for Enhanced Cancer Metalloimmunotherapy.

Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within the tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO2) nanoparticles and the STING agonist diABZI-2, which is termed A-CaO2-Zn-LNP. The release of Zn2+ from the A-CaO2-Zn-LNP and the calcium overload synergistically induced immunogenic cell death (ICD). In addition, CaO2 nanoparticles can consume H+ and release oxygen (O2) under acidic conditions. This treatment increased the pH and alleviated the hypoxia of the TME. Along with cGAS-STING activation by diABZI-2, A-CaO2-Zn-LNP ultimately results in enhanced anti-tumor systemic immunity and long-term immune memory via alleviating the immunosuppressive microenvironment. Taken together, A-CaO2-Zn-LNP offers a new nanoplatform that expands its application for cancer treatment by metalloimmunotheray.

Coordination Synergistic-Induced J-Aggregation Enhanced Fluorescent Performance of HBT-Excimers and Imaging Applications.

Developing a novel strategy to improve the optical performances of fluorescent probes is a vital factor in elevating its practical application; viz., novel biocompatible fluorescent probes with excellent multifunctions exhibited unparalleled advantages in probing functions of intracellular molecules to elucidate intracellular events in living systems. Herein, we have successfully constructed a new strategy that aggregation and coordination synergistically induce (2-hydroxylphenyl-benzothiazole) HBT derivatives to form excimers with large red-shifted fluorescence and application for insight into stress-response zinc fluctuations in living systems. We have synthesized four HBT-based derivatives and deeply investigated the response mechanism by fluorescent spectral studies, demonstrating that probes 3 and 4 showcased large red shifts in emission wavelength due to J-aggregation. More interestingly, the fluorescence of probe 4 was significantly enhanced in the presence of a zinc ion, suggesting that zinc coordination synergistically induced J-aggregation. Probe 4 was successfully applied to image zinc fluctuations in different models of living systems, proving that this probe is a powerful tool to unveil the relationship between invasive stress and diseases by monitoring endogenous zinc fluctuations.

Thermal stability and luminescence of zinc and lanthanide(Tb3+ and Ce3+) coordination polymers with pyridine-2,5-dicarboxylic acid by the WASSR method

Two sorts of inorganic-organic coordination polymers (Tb2Zn(2,5-PDC)4・10H2O(I), Ce2Zn2(2,5-PDC)5・2H2O(II))constructed by lanthanide(TbIII 、CeIII) and ligand of the pyridine-2,5-dicarboxylate have been prepared by the soft chemical synthesis method(WASSR method). The purpose of this study was to investigate optic property, thermal stability and dehydration/hydration behavior. The experimental results indicated Tb compound(I) show stronger red phosphor than Ce compound(II), but framework of crystal structure is weaker than Ce compound(II) on account of XRD patterns comparison between dehydrated compound and re-hydrated compound. The thermal stability of Ce compound(II) is better than Tb compound(I) owing to the first weight loss temperature is high to Tb compound about 200 °C.

Elucidating the role of primary and secondary sphere Zn2+ ligands in the cyanobacterial CO2 uptake complex NDH-14: The essentiality of arginine in zinc coordination and catalysis

Inorganic carbon uptake in cyanobacteria is facilitated by an energetically intensive CO2-concentrating mechanism (CCM). Specialized Type-1 NDH complexes function as a part of this mechanism to couple photosynthetic energy generated by redox reactions of the electron transport chain (ETC) to CO2 hydration. This active site of CO2 hydration incorporates an arginine side chain as a Zn ligand, diverging from the typical histidine and/or cysteine residues found in standard CAs. In this study, we focused on mutating three amino acids in the active site of the constitutively expressed NDH-14 CO2 hydration complex in Synechococcus sp. PCC7942: CupB-R91, which acts as a zinc ligand, and CupB-E95 and CupB-H89, both of which closely interact with the arginine ligand. These mutations aimed to explore how they affect the unusual metal ligation by CupB-R91 and potentially influence the unusual catalytic process. The most severe defects in activity among the targeted residues are due to a substitution of CupB-R91 and the ionically interacting E95 since both proved essential for the structural stability of the CupB protein. On the other hand, CupB-H89 mutations show a range of catalytic phenotypes indicating a role of this residue in the catalytic mechanism of CO2-hydration, but no evidence was obtained for aberrant carbonic anhydrase activity that would have indicated uncoupling of the CO2-hydration activity from proton pumping. The results are discussed in terms of possible alternative CO2 hydration mechanisms.

Highly selective fluorescence turn-on sensor for·thiol compounds detection

As a kind of commonly-used synthetic materials for many pesticides, thiol compounds, once being leaked, can cause serious harm to the environment and humans. Therefore, the efficient detection of thiol compounds is essential. In this study developed a turn-on fluorescent probe (Cu@Zn-CP) for the highly sensitive fluorescence detection of thiol compounds. The probe was constructed based on a zinc coordination polymer (Zn-CP), whose fluorescence was quenched through the effective doping of Cu2+ ions. After the introduction of methyl thioglycolate (MTC), a rapid fluorescence turn-on response was generated within 90 s with a low detection limit of 23 ppb. Even after being reused for five cycles, the sensor maintains excellent detection performance and demonstrates good recyclability. It can also detect MTC in river water, with a spike recovery rate between 98–103 %. Furthermore, the designed Cu@Zn-CP exhibits good universality for detecting multifarious thiol compounds, including L-cysteine, glutathione, monothioglycerol, and 2-hydroxy-1-ethanethiol. This result provides a potential recyclable fluorescent sensor for thiol compounds.

Imination of Sterically Unshielded o‐Quinones in the Coordination Sphere of Zinc (II)

Abstracto‐Iminoquinones bearing unshielded chelating OCCN(R) site were synthesized in high yields in the zinc coordination sphere as the neutral complexes. The stability of one‐electron‐reduced forms of these o‐iminoquinones and the distribution of the unpaired electron density in the corresponding radical anion species were studied using cyclic voltammetry and EPR spectroscopy methods

Biomaterials in Cancer Therapy: Investigating the Interaction between Kaempferol and Zinc Ions through Computational, Spectroscopic and Biological Analyses.

A complex of the natural flavonoid kaempferol with zinc (Kam-Zn) was synthesized, and its physicochemical properties were investigated using spectroscopic methods such as Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-Vis) spectroscopy and theoretical chemistry. Biological studies were conducted to evaluate the cytotoxic and antiproliferative effects of these complexes on MCF-7 breast cancer cells. Treatment with Kam 100 µM (84.86 ± 7.79%; 64.37 ± 8.24%) and Kam-Zn 100 µM (91.87 ± 3.80%; 87.04 ± 13.0%) showed no significant difference in proliferation between 16 h and 32 h, with the gap width remaining stable. Both Kam-Zn 100 μM and 200 μM demonstrated effective antiproliferative and cytotoxic activity, significantly decreasing cell viability and causing cell death and morphology changes. Antioxidant assays revealed that Kam (IC50 = 5.63 ± 0.06) exhibited higher antioxidant potential compared to Kam-Zn (IC50 = 6.80 ± 0.075), suggesting that zinc coordination impacts the flavonoid's radical scavenging activity by the coordination of metal ion to hydroxyl groups. Computational studies revealed significant modifications in the electronic structure and properties of Kam upon forming 1:1 complexes with Zn2+ ions. Spectroscopy analyses confirmed structural changes, highlighting shifts in absorption peaks and alterations in functional group vibrations indicative of metal-ligand interactions. FT-IR and UV-Vis spectra analysis suggested that Zn coordinates with the 3-OH and 4C=O groups of ligand. These findings suggest that the Kam-Zn complex exhibits interesting antiproliferative, cytotoxic and modified antioxidant effects on MCF-7 cells, providing valuable insights into their structural and anticancer properties.

Solid-state structural transformation triggered by water in zinc(Ⅱ) coordination polymers based on 3,5-ditertbutyl-2-hydroxybenzoic acid:Structural characterization and dielectric properties

Single-crystal-to-single-crystal (SCSC) transformation provides a good platform for obtaining new functional coordination polymers. In this study, we demonstrate a violent and rapid structural transformation between two d10 coordination polymers (CPs). The complex 1 [Zn(3,5-thbzc)2(C2H6O)2] transformed into the complex 2 {[Zn(3,5-thbzc)2(H2O)2]·C3H7NO·2H2O} (where t = tbutyl, hbzc− = 2-Hydroxybenzoato) triggered by deionized water under standard temperature and pressure conditions in solid state. The transformation reaction was confirmed using single-crystal XRD, PXRD and SEM. The results showed that complex 1 adopts a bidentate chelate six-coordination mode, and complex 2 adopts a monodentate four-coordination mode. SEM clearly showed that complex 2 was in the form of random nanowire clusters, suggesting that their transformation required degradation of the entire crystal structure. UV–Vis–NIR spectra were used to calculate the band gaps of complexes 1 and 2, which demonstrated wide-bandgap semiconductor-like materials with ∼3.2 eV band gap widths. The results of dielectric studies of complex 1 revealed that it possessed a medium dielectric constant (κ = 6.08 at 1 kHz), while complex 2 displayed an even higher dielectric constant (κ = 7.97 at 1 kHz) at room temperature. Interestingly, parent complex 1 exhibited a small ladder-like dielectric anomaly at 188 °C, while progeny complex 2 did not. This paper describes a new strategy for preparing adjustable functional dielectric materials.

Zinc(II) coordination compound with N′-(pyridin-2-ylmethylene)nicotinohydrazide: Synthesis, crystal structure, computational and cytotoxicity studies

In this work, we report on the synthesis of a novel zinc(II) coordination compound [ZnL2] (1), which was readily obtained from the reaction of Zn(OAc)·2H2O and N′-(pyridin-2-ylmethylene)nicotinohydrazide (HL) in methanol. Recrystallization of 1 from dimethylformamide under ambient conditions allowed to produce yellow block-like crystals of 1·H2O. Complex 1·H2O was characterized by FT-IR and 1H NMR spectroscopy, while its optical properties were studied by UV–vis and spectrofluorimetry in methanol. The crystal structure of the title complex was revealed by single crystal X-ray diffraction and further explored in detail by the Hirshfeld surface analysis. Theoretical investigations based on the DFT calculations have also been applied to show the electronic properties of complex 1. The antitumor activities of the parent ligand HL and complex 1 were studied using Dalton's lymphoma malignant cancer model. Both compounds were found to induce concentration-dependent cytotoxicity and apoptotic cell death, leading to a decrease in cell viability, body weight, and tumor volume in mice with the superior activity of complex 1 over HL. Mice treated with complex 1 demonstrated an increase in life span with a survival period of 23 days. Finally, using a molecular docking approach, we have probed complex 1 to inhibit the recombinant mouse tumor-necrosis factor alpha (mTNF).

Probing the active site of Class 3 L-asparaginase by mutagenesis. I. Tinkering with the zinc coordination site of ReAV.

ReAV, the inducible Class-3 L-asparaginase from the nitrogen-fixing symbiotic bacterium Rhizobium etli, is an interesting candidate for optimizing its enzymatic potential for antileukemic applications. Since it has no structural similarity to known enzymes with this activity, it may offer completely new ways of approach. Also, as an unrelated protein, it would evade the immunological response elicited by other asparaginases. The crystal structure of ReAV revealed a uniquely assembled protein homodimer with a highly specific C135/K138/C189 zinc binding site in each subunit. It was also shown before that the Zn2+ cation at low and optimal concentration boosts the ReAV activity and improves substrate specificity, which indicates its role in substrate recognition. However, the detailed catalytic mechanism of ReAV is still unknown. In this work, we have applied site-directed mutagenesis coupled with enzymatic assays and X-ray structural analysis to elucidate the role of the residues in the zinc coordination sphere in catalysis. Almost all of the seven ReAV muteins created in this campaign lost the ability to hydrolyze L-asparagine, confirming our predictions about the significance of the selected residues in substrate hydrolysis. We were able to crystallize five of the ReAV mutants and solve their crystal structures, revealing some intriguing changes in the active site area as a result of the mutations. With alanine substitutions of Cys135 or Cys189, the zinc coordination site fell apart and the mutants were unable to bind the Zn2+ cation. Moreover, the absence of Lys138 induced atomic shifts and conformational changes of the neighboring residues from two active-site Ser-Lys tandems. Ser48 from one of the tandems, which is hypothesized to be the catalytic nucleophile, usually changes its hydration pattern in response to the mutations. Taken together, the results provide many useful clues about the catalytic mechanism of the enzyme, allowing one to cautiously postulate a possible enzymatic scenario.

A twofold interpenetrated two-dimensional zinc(II) coordination polymer for the highly sensitive detection of nitrofurantoin in aqueous medium.

A novel ZnII coordination polymer, namely, poly[{μ2-bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]methanone-κ2N3:N3'}(μ2-5-bromobenzene-1,3-dicarboxylato-κ2O1:O3)zinc(II)], [Zn(C8H3BrO4)(C21H18N4O)]n or [Zn(Br-BDC)(MIPMO)]n, (I), has been synthesized by the solvothermal method using 5-bromoisophthalic acid (Br-H2BDC), bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]methanone (MIPMO) and Zn(NO3)2·6H2O. Structure analysis showed that compound (I) displays twofold parallel interwoven sql nets. Fluorescence experiments confirmed that the compound can sensitively and selectively detect nitrofurantoin (NFT) in aqueous medium. In addition, the possible fluorescence quenching mechanisms of compound (I) toward NFT are investigated.

The effect of ligand/ metal-ligand ratio on the structural architectures of five different 1D zinc(II) coordination polymers with pyridyl derivative ligands

Five coordination compounds, [Zn(bppc)Cl]n·0.5nH2O (1) [Zn2(bppc)2(suc)]n (2), [Zn(dppb)Cl]n·nH2O (3) [Zn(dppb)Cl]n (4) [Zn2(dppb)2(bdc)]n·2nH2O(5) (Hbppc =2,6-bis(pyrazin-2-yl)pyridine-4-carboxylic acid, H2suc=succinic acid, Hdppb=4-(2,6-di(pyrazin-2-yl)pyridine-4-yl)-benzoic acid, H2bdc=1,4-benzenedicarboxylic acid), with the same one dimensions but different patterns have been hydrothermally synthesized and structurally characterized. Single crystal X-ray analysis revealed that compound 1 shows one-dimensional wave chain structure, compound 2 to 5 show one-dimensional ladder chain structure, one-dimensional V-shaped chain structure, one-dimensional linear chain structure and one-dimensional A-shaped chain structure, respectively. The structure differences of 1–5 show that ligand including auxiliary ligand and metal-ligand ratio have important influence on the final structures. Additionally, the luminescent properties of 1–5 have been investigated with fluorescent spectra in the solid state and fluorescence sensing experiments show that compound 1 exhibit a great selectivity and sensitivity for detection of Cu2+ion and nitrobenzene.