A ternary nucleotide-lanthanide coordination nanoprobe for ratiometric fluorescence detection of ciprofloxacin.

Ciprofloxacin (CIP) is a widely used broad-spectrum antibiotic and has been associated with various side effects, making its accurate detection crucial for patient safety, drug quality compliance, and environmental and food safety. This study presents the development of a ternary nucleotide-lanthanide coordination nanoprobe, GMP-Tb-BDC (GMP: guanosine 5'-monophosphate, BDC: 2-amino-1,4-benzenedicarboxylic acid), for the sensitive and ratiometric detection of CIP. The GMP-Tb-BDC nanoprobe was constructed by incorporating the blue-emissive ligand BDC into the Tb/GMP coordination polymers. Upon the addition of CIP, the fluorescence of terbium ion (Tb3+ ) was significantly enhanced due to the coordination and fluorescence sensitization properties of CIP, while the emission of the BDC ligand remained unchanged. The nanoprobe demonstrated good linearity in the concentration range of 0-10 µM CIP. By leveraging mobile phone software to analyze the color signals, rapid on-site analysis of CIP was achieved. Furthermore, the nanoprobe exhibited accurate analysis of CIP in actual drug and milk samples. This study showcases the potential of the GMP-Tb-BDC nanoprobe for practical applications in CIP detection.

d-Orbital Reconstructions Forced by Double Bow-Shaped Deformations and Second Coordination Sphere Effects of Cu(II) Heme Analogs in HER.

Both geometric architecture and electronic configurations of heme proteins contribute to its activity. In this work we designed and synthesized a series of four copper(II) porphyrin complexes (4-, 3-, 2- and 1-Cu) where the molecular conformations are modulated by a pair of stepwise shortened straps on the same porphyrin side (cis-ortho) to give double bow-shaped skeletons. Single crystal structures demonstrate that the straps gradually increase the saddle deformation and the deviation of the metal centers, which is in accordance with two, unusual d-orbital reconstructions of two different ground states, as revealed by 4 K EPR and DFT calculations. In the study of the electrocatalytic hydrogen evolution reaction (HER), 1-Cu, with the shortest straps, showed the most apparent improvement of activity. Second coordination sphere (SCS) effects created by the double bow-shaped architecture and the strong saddle porphyrin core in 1-Cu are found to play key roles in proton trapping during the catalytic process. The work contributes a novel strategy to improve the catalytic performance of heme analogs through ligand geometric modulation.

Porous materials formed by four self-construction processes.

Multiple self-construction behavior of cyclic oligoesters is described. Rigid braces and elastic hinges are periodically incorporated into these cyclomers, which enables these rings to form various topological frameworks, such as holes, caves or cages with different sizes and shapes, through self-folding. Among them, the cave-type cyclomer self-assembles into nanotunnels and then forms porous materials via self-packing of these tunnels. This discovery provides a new perspective for the construction of novel materials aided by multiple supramolecular effects. In this work, the simplest rigid brace components and ones with soft hinges were chosen to construct cyclomers to confirm the supramolecular strategy.

De Novo Development of a Universal Biosensing Platform by Rapid Direct Native Protein Modification.

An innovative biosensing assay was developed for simplified, cost-effective, and sensitive detection. By rapid, direct treatment of target proteins with iron porphyrin (TPPFe) in situ, a carboxyl group of amino acid conjugates with an Fe atom of the TPPFe molecule, forming a stable protein complex. We have shown that this complex not only maintains the integrity and functions of original proteins but also acquires peroxidase activity that can turn TMB to a comparably visible signal like that in ELISA. This study is unique since such conversion is difficult to achieve with standard chemical modification or molecular biology methods. In addition, the proposed immunoassay is superior to traditional ELISA as it eliminates an expensive and complicated cross-linking process of an enzyme-labeled antibody. From a practical point of view, we extended this assay to rapid detection of clinically relevant proteins and glucose in blood samples. The results show that this simple immunoassay provides clinical diagnosis, food safety, and environmental monitoring in an easy-to-implement manner.

An Antifungal Polycyclic Tetramate Macrolactam, Heat-Stable Antifungal Factor (HSAF), Is a Novel Oxidative Stress Modulator in Lysobacter enzymogenes.

Polycyclic tetramate macrolactams (PoTeMs) are a fast-growing family of antibiotic natural products found in phylogenetically diverse microorganisms. Surprisingly, none of the PoTeMs have been investigated for potential physiological functions in their producers. Here, we used heat-stable antifungal factor (HSAF), an antifungal PoTeM from Lysobacter enzymogenes, as a model to show that PoTeMs form complexes with iron ions, with an association constant (Ka ) of 2.71 × 106 M-1 The in vivo and in vitro data showed formation of 2:1 and 3:1 complexes between HSAF and iron ions, which were confirmed by molecular mechanical and quantum mechanical calculations. HSAF protected DNA from degradation in high concentrations of iron and H2O2 or under UV radiation. HSAF mutants of L. enzymogenes barely survived under oxidative stress and exhibited markedly increased production of reactive oxygen species (ROS). Exogenous addition of HSAF into the mutants significantly prevented ROS production and restored normal growth in the mutants under the oxidative stress. The results reveal that the function of HSAF is to protect the producer microorganism from oxidative damage rather than as an iron-acquisition siderophore. The characteristic structure of PoTeMs, a 2,4-pyrrolidinedione-embedded macrolactam, may represent a new iron-chelating scaffold of microbial metabolites. The study demonstrated a previously unrecognized strategy for microorganisms to modulate oxidative damage to the cells.IMPORTANCE PoTeMs are a family of structurally distinct metabolites that have been found in a large number of bacteria. Although PoTeMs exhibit diverse therapeutic properties, the physiological function of PoTeMs in the producer microorganisms had not been investigated. HSAF from Lysobacter enzymogenes is an antifungal PoTeM that has been subjected to extensive studies for mechanisms of biosynthesis, regulation, and antifungal activity. Using HSAF as a model system, we here showed that the characteristic structure of PoTeMs, a 2,4-pyrrolidinedione-embedded macrolactam, may represent a new iron-chelating scaffold of microbial metabolites. In L. enzymogenes, HSAF functions as a small-molecule modulator for oxidative damage caused by iron, H2O2, and UV light. Together, the study demonstrated a previously unrecognized strategy for microorganisms to modulate oxidative damage to the cells. HSAF represents the first member of the fast-growing PoTeM family of microbial metabolites whose potential biological function has been studied.

Horizontal and Vertical Push Effects in Saddled Zinc Porphyrin Complexes: Implications for Heme Distortion.

A heme oxygen binding behavior was described through a unique geometric and electronic comparison of zinc porphyrin complexes. In this work, a charge transfer model for saddled metalloporphyrin complexes outlined the push effects of the ring nonplanarity and axial imidazole, and the pull effect of the axial dioxygen. The origin and role of the horizontal (ring nonplanarity) push effect and its relationship to the vertical (axial ligand) push/pull effect and its contribution to dioxygen binding were considered from the perspectives of crystal structures, theoretical calculations, and bathochromic shifts. Single-point energy and molecular orbital calculations starting from crystal structures were used to obtain the electronic structures of zinc porphyrin complexes. This study not only revealed that the electronic behavior of metalloporphyrins is driven by ring nonplanarity and axial ligation but also afforded new insight into the oxygen carrier mechanism in heme.

Electron Transfer and Geometric Conversion of Co-NO Moiety in Saddled Porphyrins: Implications for Trigger Role of Tetrapyrrole Distortion.

The electrons of NO and Co are strongly delocalized in normal {Co-NO}8 species. In this work, {Co-NO}8 complexes are induced to convert from (CoII)+•-NO• to CoIII-NO- by a core contraction of 0.06 Šin saddled cobalt(II) porphyrins. This intramolecular electron transfer mechanism indicates that nonplanarity of porphyrin is involved in driving conversion of the NO units from electrophilic NO• as a bent geometry to nucleophilic NO- as a linear geometry. This implies that distortion acts as a trigger in enzymes containing tetrapyrrole. The electronic behaviors of the CoII ions and Co-NO moieties were confirmed by X-ray crystallography, EPR spectroscopy, theoretical calculation, UV-vis and IR spectroscopy, and electrochemistry.

Geometric deconstruction of core and electron activation of a π-system in a series of deformed porphyrins: mimics of heme.

The predominant distortion of heme is responsible for its electronic activity, catalytic ability and spectral properties. In this work, altogether 12 new X-ray structures of saddled, waved and ruffled porphyrins are reported. Three types of deformed porphyrins as mimics of heme were evaluated and analyzed by geometric deconstruction, spectral comparison, and electrochemical tracking, which shows a unique relationship of deformation fashions and distortion degree to the geometry of the core and electron transfer ability of rings in these enzyme containing porphyrins. These mimics can adjust their core geometry for changing the structures of potential metals; while for rings themselves, they can also regulate the electron activity by switching the HOMO of the large π systems. These deformed porphyrins can be used as ideal mimics for heme. These findings help us to understand the principle and contribution of these deformations to electron transfer in catalytic oxidation and photoreactions. The nonplanar mimics have been synthesized through a modular synthetic approach under Adler-Longo or Lindsey condensation conditions.

Fractional transfer of a free unpaired electron to overcome energy barriers in the formation of Fe(4+) from Fe(3+) during the core contraction of macrocycles: implication for heme distortion.

The free unpaired electron in Fe(3+) ions cannot be directly removed, and needs a transfer pathway with at least four steps to overcome the high energy barriers to form Fe(4+) ions. Fine changes in the electronic structure of Fe(3+) ions on spin conversion were identified through a deeper analysis of the diffraction, spectral and electrochemical data for six non-planar iron porphyrins. Fe(3+) ions can form four d electron tautomers as the compression of the central ion is increased. This indicates that the Fe(3+) ion undergoes a multistep electron transfer where the total energy gap of electron transfer is split into several smaller gaps to form high-valent Fe(4+) ions. We find that the interchange of these four electron tautomers is clearly related to the core size of the macrocycle in the current series. The large energy barrier to produce iron(iv) complexes is overcome through a gradient effect of multiple energy levels. In addition, a possible porphyrin Fe(3+)˙ radical may be formed from its stable isoelectronic form, porphyrin Fe(3+), under strong core contraction. These results indicate the important role of heme distortion in its catalytic oxidation functions.

Geometry and temperature dependence of meso-aryl rotation in strained metalloporphyrins: adjustable turnstile Molecules.

The rotation of meso-aryl groups in porphyrins depends on the degree of macrocyclic distortion and is also influenced by the surrounding temperature. Dynamic NMR methods and crystal structures of series of nonplanar metalloporphyrins reveal that macrocyclic distortion lowers the rotational barrier by weakening the nonbinding interactions of neighboring groups, while increased temperature allows the rotational barrier to be overcome more readily. Two empirical methods are developed to acquire the rotational barrier. This type of strained molecule can act as an adjustable molecular turnstile through adjusting the degree of macrocyclic distortion and changing the surrounding temperature.

Opposing influences of ruffling and doming deformation on the 4-N cavity size of porphyrin macrocycles: the role of heme deformations revealed.

Ruffle- and dome-type porphyrins were developed as model systems to investigate the role of deformation mode and degree of distortion in heme. Their crystal structures revealed that as the degree of distortion increases, cavity size can be contracted in the ruffle mode and expanded in the dome mode, and the size of cavity can exceed the limit of free metal ions from the fourth period (see scheme).

Enhanced Mimetic Enzyme Activity of Phosphorylated Porphyrin Nanocomposite Induced by Localized Surface Plasmon Resonance for Colorimetric Assay.

Plasmon-enhanced light harvesting has been of great interest to enhance the catalytic efficiency of some composites or hybrids. The enhanced peroxidase-like activity of phosphorylated iron(III) porphyrin (TPPFe(III))-based nanocomposite, induced by localized surface plasmon resonance for a colorimetric assay, was developed in this study. Firstly, a phosphate group modification strategy was adopted to synthesize water-soluble iron(III) porphyrin materials. Then, the as-synthesized TPPFe(III) was covalently attached to core-shell gold nanorods (GNRs), GNR@Au2S/AuAgS, to form TPPFe(III)-GNR@Au2S/AuAgS nanocomposite, which shows greatly enhanced peroxidase-like activity compared to TPPFe(III). A mechanism for the enhanced peroxidase-like activity of TPPFe(III)-GNR@Au2S/AuAgS was proposed, which results from a synergic effect of hot electrons excited by localized surface plasmon resonance and photogenerated electrons of the TPPFe(III), verified by experiments. Furthermore, a fast colorimetric assay for the detection of H2O2 and glucose was established based on the unique property of TPPFe(III)-GNR@Au2S/AuAgS. This colorimetric assay was applied to determine practical human serum samples; satisfactory results demonstrate this method has high accuracy. The present study would not only provide some insights into the mechanism of plasmon-activated enzyme-like reactions, but also offer new strategies for improving the catalytic activity of a mimetic enzyme.

A novel soluble tin(IV) porphyrin modified single-walled carbon nanotube nanohybrid with light harvesting properties.

A dihydroxotin(IV) porphyrin functionalized single-walled carbon nanotubes (SWNTs) nanohybrid is obtained. Solubility of the nanohybrid in organic solvents is determined by UV-Vis-NIR absorption spectroscopy. Electron absorption and fluorescence spectra investigations demonstrate that efficient electron transfer occurs within the nanohybrid at the photoexcited state and the charge-separated state of the nanohybrid is observed by transient absorption spectrum. The results illustrate that this soluble electron donor-acceptor nanohybrid might be a good candidate as a light harvesting material in molecular photoelectronic devices.

TMPyP Inhibits Amyloid-ß Aggregation and Alleviates Amyloid-Induced Cytotoxicity.

The aggregation or misfolding of amyloid-ß (Aß) is a major pathological hallmark of Alzheimer's disease (AD). The regulation of Aß aggregation is thought to be an effective strategy for AD treatment. The capability of a water-soluble porphyrin, 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP), to inhibit Aß aggregation and to lower Aß-induced toxicity was demonstrated. As evidenced by surface plasmon resonance and circular dichroism, TMPyP can not only disrupt Aß aggregation but also disassemble the preformed Aß aggregates. The atomic force microscopy imaging proves that TMPyP inhibits the formation of both oligomers and fibrils. Molecular dynamic simulations provide an insight into the interaction between TMPyP and Aß at the molecular level. The half-maximal inhibitory concentrations of TMPyP acting on the oligomers and fibrils were determined to be 0.6 and 0.43 µM, respectively. As a member of porphyrin family, TMPyP is of rather low cytotoxicity, and the cytotoxicity of the Aß aggregates was also relieved upon coincubation with TMPyP. The excellent performance of TMPyP thus makes it a potential drug candidate for AD therapy.

Fixation of Zinc(II) Ion to Dioxygen in a Highly Deformed Porphyrin: Implications for the Oxygen Carrier Mechanism of Distorted Heme.

Three saddle-type nonplanar zinc porphyrins strapped by two short alkyl linkers have been synthesized. The deformation induced by the linkers can cause a spectral red shift of >30 nm compared with the absorption maxima of regular porphyrins and can also regulate the electronic structure of the central zinc(II) ion. The zinc(II) ion then complexes and activates a free dioxygen to form a superoxide group ligand by enlarging the splitting of energy levels of d orbitals under strong core deformation. The fixation of dioxygen can be reasonably explained by the Dewar-Chatt-Duncanson model. These results indicate that this type of saddle porphyrin has the potential to be used as a new model system of heme.

Fine-Tuning of Electronic Structure of Cobalt(II) Ion in Nonplanar Porphyrins and Tracking of a Cross-Hybrid Stage: Implications for the Distortion of Natural Tetrapyrrole Macrocycles.

The core size of the porphyrin macrocycles was closely related to their stability of the different electron structure in the central metal ion. Cobalt(II) ions can undergo a conversion in electron configurations upon N4 core contraction of 0.05 Šin nonplanar porphyrins, and these ions still maintain low spin forms after and before conversion. The structural fine-tuning can induce the appearance of a cross-hybrid stage [d(x(2)-y(2))sp(2) ↔ d(z(2))sp(2)] based on quadrilateral coordination of the planar core. The results indicate that the configuration conversion plays a key role in electron transfer in redox catalysis involving cobalt complexes. The electronic properties of six monostrapped cobalt(II) porphyrins were investigated by spectral, paramagnetic, and electrochemical methods. The macrocyclic deformations and size parameters of Co-containing model compounds were directly obtained from their crystal structures.

Conversion of electron configuration of iron ion through core contraction of porphyrin: implications for heme distortion.

It was demonstrated experimentally that nonplanar iron porphyrins can be induced to undergo a conversion in their electronic configuration to form a cross-hybrid transition by compressing the macrocyclic core size for the central metal ion. A series of monostrapped iron porphyrins were used as model systems, and their electronic properties were probed using electron spin resonance and differential spectral analyses. These results indicate that the formation of a cross-hybrid transition stage is related to the stability of the high-valence state and potent oxidizing ability of the central iron ion.

Direct synthesis of anti-1,3-diols through nonclassical reaction of aryl Grignard reagents with isopropenyl acetate.

A series of symmetrical aromatic 1,3-diols were efficiently synthesized from substituted aryl Grignard reagents and isopropenyl acetate in a one-step reaction that formed anti products as the major species. Both experimental and theoretical studies suggested that the reaction involves the formation of a relatively stable intermediate E containing a six-membered ring from intermediate A. The stereoselectivity of the reactions and the molecular structure of the products were confirmed by NMR spectroscopy, X-ray diffraction, and gas chromatography.

Hybrid orbital deformation (HOD) effect and spectral red-shift property of nonplanar porphyrin.

A series of 5,15-meso,meso-strapped nonplanar porphyrins with different degrees of ruffling distortion, as a model system, have been synthesized and characterized. The spectral red-shift of the nonplanar porphyrins was experimentally demonstrated to mainly originate from the hybrid orbital deformation (HOD) effect due to the distortion in the tetrapyrrole macrocycle, which confirmed previous explanations to the red-shift phenomenon.

Bis(zinc porphyrin) bridged by benzo orthocarbonates as a conformational switch under regulation of DABCO and a Cu+ ion.

A tweezer-type bis(zinc porphyrin) bridged by benzo orthocarbonates was synthesized and applied as a molecular conformational switch under regulation of DABCO and a Cu(+) ion. The switch property has been confirmed by (1)H NMR, UV-vis spectral titration, and HR-MS spectra method.