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[Display omitted] • Modification solves the problem of water solubility of hematin. • Multi-level structured nanoparticles were prepared using microfluidic technology. • Multi-level structured nanoparticles exhibit excellent chemiluminescence signals. • A chemiluminescence immunosensor was constructed for sensitive detection of CEA. The properties of nanomaterials are heavily influenced by their size effects. Utilizing the self-assembly principle offers a promising avenue for crafting innovative nanomaterials, yet controlling this process at the microscopic level presents significant challenges, hindering effective regulation of nanomaterial morphology. Microfluidic technology, however, offers precise control over fluid velocities within microchannels, enabling micro-level manipulation. In this study, we synthesized amphiphilic molecules HP (Hematin@NH 2 -PEG-COOH) through hematin modification, leveraging microfluidic techniques to encapsulate luminol within HP molecules, resulting in the formation of highly efficient chemiluminescence (CL) HPL (HP@Luminol) nanoparticles. The size effects and intricate multi-level structures achieved during encapsulation endowed these nanoparticles with enhanced catalytic capabilities for CL. Finally, we used HPL nanoparticles as luminescent markers to develop a CL immunosensor for the sensitive detection of the tumor marker carcinoembryonic antigen (CEA), achieving satisfactory results. This innovative approach not only expands the repertoire of nanomaterial design and synthesis but also offers a practical solution for sensitive biomarker detection. Overall, this research introduces a novel strategy for designing and fabricating advanced nanomaterials, underscoring the potential of microfluidic technology in nanoscience and biosensing applications. [ABSTRACT FROM AUTHOR]

Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH−) and hemin (liganded with Cl−)—are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe3. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation. Hematin and hemin at nanomolar concentrations increased [Ca2+]i in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca2+]i. Both compounds triggered acute phosphatidylserine exposure on the membrane surface, reversible after 60 min of incubation. A comparison of hematin and hemin effects on RBCs revealed that hematin is a more reactive toxic metabolite than hemin towards human RBCs. The toxic effects of heme derivatives were reduced and even reversed in the presence of albumin, indicating the presence in RBCs of the own recovery system against the toxic effects of heme derivatives. [ABSTRACT FROM AUTHOR]

Crop growth and yield are affected by salinity, which causes oxidative damage to plant cells. Plants respond to salinity by maintaining cellular osmotic balance, regulating ion transport, and enhancing the expression of stress-responsive genes, thereby inducing tolerance. As a byproduct of heme oxygenase (HO)-mediated degradation of heme, carbon monoxide (CO) regulates plant responses to salinity. This study investigated a CO-mediated salt stress tolerance mechanism in sorghum seedlings during germination. Sorghum seeds were germinated in the presence of 250 mM NaCl only, or in combination with a CO donor (1 and 1.5 μM hematin), HO inhibitor (5 and 10 μM zinc protoporphyrin IX; ZnPPIX), and hemoglobin (0.1 g/L Hb). Salt stress decreased the germination index (47.73%) and root length (74.31%), while hydrogen peroxide (H2O2) (193.5%), and proline (475%) contents increased. This increase correlated with induced HO (137.68%) activity and transcripts of ion-exchanger and antioxidant genes. Salt stress modified vascular bundle structure, increased metaxylem pit size (42.2%) and the Na+/K+ ratio (2.06) and altered primary and secondary metabolites. However, exogenous CO (1 μM hematin) increased the germination index (63.01%) and root length (150.59%), while H2O2 (21.94%) content decreased under salt stress. Carbon monoxide further increased proline (147.62%), restored the vascular bundle structure, decreased the metaxylem pit size (31.2%) and Na+/K+ ratio (1.46), and attenuated changes observed on primary and secondary metabolites under salt stress. Carbon monoxide increased HO activity (30.49%), protein content, and antioxidant gene transcripts. The alleviatory role of CO was abolished by Hb, whereas HO activity was slightly inhibited by ZnPPIX under salt stress. These results suggest that CO elicited salt stress tolerance by reducing oxidative damage through osmotic adjustment and by regulating the expression of HO1 and the ion exchanger and antioxidant transcripts. [ABSTRACT FROM AUTHOR]

Introduction: Porphyrias are metabolic disorders caused by enzymatic alterations in the biosynthesis of the heme group of heme proteins. The clinical spectrum of porphyrias is associated with the location of the damage in the heme formation chain, which can range from neurovisceral manifestations to cutaneous alterations related to photosensitivity. The diagnosis of this pathology can be difficult since it is a rare disease and the symptoms are nonspecific. Objectives: The present study reports the diagnosis steps and clinical suspicion of a case of acute intermittent porphyria. Case Report: A 23-years-old male patient initially presented with nonspecific abdominal pain to the Emergency Room of Hospital João XXIII (Belo Horizonte/MG). The diagnostic investigation became more directed because of the positive family history for porphyria; until this information was provided, approaching the case was challenging. Diagnostic accuracy is essential considering the risk of using medications commonly used in the Emergency Room and which are aggravating for porphyria. The case was managed with symptom support and caloric intake until the medication (hematina) was acquired through judicialization. Conclusion: Acute hepatic porphyrias are a group of rare diseases with severe and nonspecific manifestations. However, patients with unexplained abdominal pain, mainly associated with neuropsychiatric symptoms and positive family history, should be screened for urinary porphyrins because recognizing the disease is essential, and hematin therapy should be promptly introduced.

In this work, silver nanoparticles (AgNPs) were synthesized via two different routes. The first route was based on the Creighton method (chemical reduction), used aniline as a passivating agent and NaBH4 as a reducing agent, and led to a green nanoparticle solution with an average particle size of 23 ​± ​11 ​nm and a plasmonic resonance with a maximum at 376 ​nm. The second route was the hydrothermal method, in which aniline was used to reduce the metal salt and stabilize the nanoparticles; this provided a pink solution of nanoparticles with an average particle size of 11 ​± ​5 ​nm, and a plasmon resonance with a maximum at 550 ​nm. Aniline was polymerized by using hematin as the catalyst, and FT-IR, RAMAN, and NMR spectroscopy were used to characterize the structure. In addition, the PANI/AgNP composite was synthesized, and it exhibited a higher conductivity of 0.28 ​S/cm relative to that of PANI (0.05 ​S/cm).

Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH−) and hemin (liganded with Cl−)—are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe3. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation. Hematin and hemin at nanomolar concentrations increased [Ca2+]i in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca2+]i. Both compounds triggered acute phosphatidylserine exposure on the membrane surface, reversible after 60 min of incubation. A comparison of hematin and hemin effects on RBCs revealed that hematin is a more reactive toxic metabolite than hemin towards human RBCs. The toxic effects of heme derivatives were reduced and even reversed in the presence of albumin, indicating the presence in RBCs of the own recovery system against the toxic effects of heme derivatives.

Crop growth and yield are affected by salinity, which causes oxidative damage to plant cells. Plants respond to salinity by maintaining cellular osmotic balance, regulating ion transport, and enhancing the expression of stress-responsive genes, thereby inducing tolerance. As a byproduct of heme oxygenase (HO)-mediated degradation of heme, carbon monoxide (CO) regulates plant responses to salinity. This study investigated a CO-mediated salt stress tolerance mechanism in sorghum seedlings during germination. Sorghum seeds were germinated in the presence of 250 mM NaCl only, or in combination with a CO donor (1 and 1.5 μM hematin), HO inhibitor (5 and 10 μM zinc protoporphyrin IX; ZnPPIX), and hemoglobin (0.1 g/L Hb). Salt stress decreased the germination index (47.73%) and root length (74.31%), while hydrogen peroxide (H2O2) (193.5%), and proline (475%) contents increased. This increase correlated with induced HO (137.68%) activity and transcripts of ion-exchanger and antioxidant genes. Salt stress modified vascular bundle structure, increased metaxylem pit size (42.2%) and the Na+/K+ ratio (2.06) and altered primary and secondary metabolites. However, exogenous CO (1 μM hematin) increased the germination index (63.01%) and root length (150.59%), while H2O2 (21.94%) content decreased under salt stress. Carbon monoxide further increased proline (147.62%), restored the vascular bundle structure, decreased the metaxylem pit size (31.2%) and Na+/K+ ratio (1.46), and attenuated changes observed on primary and secondary metabolites under salt stress. Carbon monoxide increased HO activity (30.49%), protein content, and antioxidant gene transcripts. The alleviatory role of CO was abolished by Hb, whereas HO activity was slightly inhibited by ZnPPIX under salt stress. These results suggest that CO elicited salt stress tolerance by reducing oxidative damage through osmotic adjustment and by regulating the expression of HO1 and the ion exchanger and antioxidant transcripts.

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The low toxicity and high adsorption capacities of clay minerals make them attractive for controlled delivery applications. However, the number of controlled-release studies in the literature using clay minerals is still scarce. In this work, three different clays from the smectite group (Kunipia F, montmorillonite; Sumecton SA, saponite; and Sumecton SWN, hectorite) were successfully loaded with rhodamine B dye and functionalized with oleic acid as a gatekeeper to produce organonanoclays for active and controlled payload-release. Moreover, hematin and cyanocobalamin have also been encapsulated in hectorite gated clay. These organonanoclays were able to confine the entrapped cargos in an aqueous environment, and effectively release them in the presence of surfactants (as bile salts). A controlled delivery of 49 ± 6 μg hematin/mg solid and 32.7 ± 1.5 μg cyanocobalamin/mg solid was reached. The cargo release profiles of all of the organonanoclays were adjusted to three different release-kinetic models, demonstrating the Korsmeyer–Peppas model with release dependence on (i) the organic–inorganic hybrid system, and (ii) the nature of loaded molecules and their interaction with the support. Furthermore, in vitro cell viability assays were carried out with Caco-2 cells, demonstrating that the organonanoclays are well tolerated by cells at particle concentrations of ca. 50 μg/mL. [ABSTRACT FROM AUTHOR]

Background Hematin is a state in which hemoglobin, as petechiae, is discolored to a brown coffee color by gastric hydrochloric acid. Given the nature of hematin, a close relationship between hematin and acidity has been suggested, but has not been confirmed. We investigated the clinical significance of endoscopic finding of hematin with respect to gastric acidity. Methods A total of 501 patients were assessed for both hematin and fasting gastric juice pH by endoscopy. Endpoints were as follows: 1) the relationship between the presence of hematin and the fasting gastric juice pH; and 2) the diagnostic performance of endoscopic hematin. In addition, we performed a supplementary in vitro study to clarify the relationship between hematin formation and various acid pH levels. Results The prevalence of hematin was 31.1% (142/206), 4.6% (5/109) and 45.2% (84/186) in the H. pylori-uninfected, -infected and -eradicated groups, respectively. The mean pH of fasting gastric juice in the hematin-positive cases was significantly lower than the hematin-negative cases (mean pH 1.2, 95% confidence interval [CI] 1.1-1.3 vs. 2.7 95%CI 2.5-3.0; P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of hematin for predicting strong acidic condition (pH 1 or 2 for fasting gastric juice) were 36.0%, 98.1%, 98.7% and 29.3%, respectively. Interobserver agreement was categorized as "excellent" (k=0.88). Supplementary in vitro results showed that hematin formation was only observed at a pH=1. Conclusion Endoscopic finding of hematin represent strong gastric acidity. [ABSTRACT FROM AUTHOR]

In this work, nitrogen-doped carbon dots (NCDs) were obtained by microwave rapid preparation method with lipase and guanidine hydrochloride as precursors in only 6 min. In order to achieve high sensitivity detection of hematin, based on obtained NCDs as a nanoprobe, a new detection method based on photoluminescence (PL) change was developed. Further studies have shown that the sensing strategy relied on the inner filter effect to selectively quench the PL emission of NCDs at 379 nm by hematin under 320 nm excitation. The nanoprobe had a wide linear range (0.2–13 μmol/L) and a detection limit of 0.07 μmol/L. The method was effectively applied to the identification of hematin in human blood samples. The proposed nanoprobe has the characteristics of simple and efficient design. It can achieve rapid and accurate detection, which is very suitable for real-time analysis of blood samples to facilitate diagnosis. [Display omitted] • The microwave method is used to design blue-emitting nitrogen -doped CDs (NCDs). • NCDs are prepared using lipase and guanidine hydrochloride as carbon and nitrogen sources • NCDs can be used as a sensor for quantitative detection of hematin. [ABSTRACT FROM AUTHOR]

Jean-Baptiste Paul Cazeneuve (1852-1934) was a successful a French physician, chemist, and politician that carried basic research of physiological subjects and vegetable principles. He demonstrated that the Guilliermond process (based on the direct action of lime on the vegetable matter) reduced substantially the time required to extract and separate alkaloids as well as a variety of first principles. He demonstrated it by extracting alkaloids such as strychnine, solanine, quassin, cocaine, veratrine, rhoeadine, and active principles like catechin. He was the first to isolate pterocarpin from red sandalwood and to show with Hugounenq that this principle was actually a mixture of two principles, homopterocarpin and pterocarpin. They also determined their chemical and physical properties, including their composition. Latour and Cazeneuve demonstrated that catechin was the astringent agent of mahogany, and Cazeneuve and Haddon determined the properties and composition of caffeinic acid. Cazeneuve studied in detail hematin, the normal coloring substance of blood, developed a fast process for separating it, and concluded that it contained iron. [ABSTRACT FROM AUTHOR]

Sulfhydryl oxidase was studied using a spectrofluorometric assay. The current protocol operates by using a combination of hemoglobin (HB) and hematin (HT) as a peroxidase mimic to catalyze the H2O2-dependent oxidation of thiamine. The response surface methodology (RSM) is used to optimize the new method. The current method is very accurate, sensitive, and linear up to 200 IU. When compared to the colorimetric method, the method produced a satisfactory correlation. The novel protocol is being used to evaluate asthenospermic patients' and fertile men's seminal sulfhydryl oxidase activity. The current protocol was used to determine reference values for seminal sulfhydryl oxidase activity. Due to the fact the newly developed spectrofluorometric method is more sensitive and precise than other colorimetric methods, and because thiamine is less expensive than other types of probes used in colorimetric and spectrofluorometric methods, it is likely to find widespread use among scientists studying sulfhydryl oxidase activity in biological tissues. The present method's analytical recovery yielded high specific findings. [ABSTRACT FROM AUTHOR]

Pooled Immunoglobulin G (IgG), hematin and the membrane-disruptive amphipathic peptide melittin have received attention as powerful biomacromolecules for biomedical and pharmacology applications. Their action on surface properties, oxidation status and epifluorescence properties measured in vitro provide useful information about the functional activity of upper biomacromolecules in erythrocytes in vivo. The hemolysis of erythrocyte membranes, as well as changes in hematocrit and the morphology of erythrocytes, was investigated here via fluorescence microscopy using FITC-concanavalin A binding to cells. The effect of melittin on the membrane capacitance and resistance of model lipid bilayers was probed via electrochemical impedance spectroscopy. Lipid bilayer capacitance was higher in the presence of 0.10 g/L melittin compared to that in the control, which is likely related to bilayer thinning and alterations of the dielectric permittivity of melittin-treated membranes. The biomolecule interactions with red blood cells were probed in physiological media in which the surface of erythrocyte membranes was negatively charged. Surface parameters of erythrocytes are reported upon IgG/hematin and IgG/melittin treatment. Pooled IgG in the presence of melittin, preincubated IgG/hematin preparations promoted a significant decrease in the electrokinetic potential of erythrocytes (Rh-positive). A malondialdehyde (MDA) assay revealed a high rate of lipid peroxidation in erythrocytes treated with IgG/hematin or IgG/melittin preparations. This finding might be a result of pooled IgG interactions with the hematin molecule and the subsequent conformational changes in the protein molecule altering the electrokinetic properties of the erythrocyte membrane related to the Rh group type of erythrocytes. The pooled IgG and hematin are reported to have important consequences for the biophysical understanding of the immunopathological mechanisms of inflammatory, autoimmune and antibody-mediated pathological processes.

The luminol–H 2 O 2 system is crucial in the field of chemiluminescence (CL) analysis. However, luminol exhibits improved solubility and luminescence only in an alkaline environment, and its preparation process is cumbersome. This inconvenience highlights the need for developing a simple and universally applicable method in this regard. This study integrates luminol and a catalyst into metal–organic frameworks (MOFs) for fabrication of functionalised MOF nanoparticles. Further, PEGylated hematin (PEG = polyethylene glycol) was prepared. This modification with PEG enhanced the catalytic properties of hematin and facilitated the formation of zeolitic imidazole framework-8 nanoparticles. Furthermore, the built-in catalyst enhanced the CL in terms of strength and persistence. These MOF nanoparticles were used as signal markers to fabricate a sandwich-type CL immunosensor for detection of carcinoembryonic antigen, which is a disease marker, following which highly satisfactory analytical test results are obtained. This approach of integrating luminophores and catalysts offers a new idea for generating novel materials in the CL analysis field. • An amphiphilic polymer was prepared by self-assembly of PEG and hematin. • One-step integration of catalyst and luminol using MOF and application to chemiluminescence immunoassay. • In non-alkaline conditions, Luminol can also produce a strong chemiluminescent signal. • The sensor is sensitive to detect CEA with a limit of detection of 0.40 pg·mL−1 and has good specificity. [ABSTRACT FROM AUTHOR]

BackgroundRecent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects.MethodsBetween September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US.ResultsMost subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks.ConclusionsAcute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.

The low toxicity and high adsorption capacities of clay minerals make them attractive for controlled delivery applications. However, the number of controlled-release studies in the literature using clay minerals is still scarce. In this work, three different clays from the smectite group (Kunipia F, montmorillonite; Sumecton SA, saponite; and Sumecton SWN, hectorite) were successfully loaded with rhodamine B dye and functionalized with oleic acid as a gatekeeper to produce organonanoclays for active and controlled payload-release. Moreover, hematin and cyanocobalamin have also been encapsulated in hectorite gated clay. These organonanoclays were able to confine the entrapped cargos in an aqueous environment, and effectively release them in the presence of surfactants (as bile salts). A controlled delivery of 49 ± 6 μg hematin/mg solid and 32.7 ± 1.5 μg cyanocobalamin/mg solid was reached. The cargo release profiles of all of the organonanoclays were adjusted to three different release-kinetic models, demonstrating the Korsmeyer–Peppas model with release dependence on (i) the organic–inorganic hybrid system, and (ii) the nature of loaded molecules and their interaction with the support. Furthermore, in vitro cell viability assays were carried out with Caco-2 cells, demonstrating that the organonanoclays are well tolerated by cells at particle concentrations of ca. 50 μg/mL.

Hematin has been used as an alternative enzyme catalyst to horseradish peroxidase (HRP) due to its iron-containing activity center. Although hematin and it derivatives have been widely used for polymerization of phenol/analine compounds, it has some drawbacks such as the limited solubility and reaction only at high pH condition. Herein, we report a nanosized biomimetic catalyst, hematin-decorated polyamidoamine dendrimer (G3.0-He) that can effectively catalyze the in situ hydrogelation of phenol-conjugated polymers under neutral pH condition. We demonstrate that G3.0-He particles are smaller than 100 nm and have excellent enzyme-mimetic functions. Interestingly, the nanosized catalyst is not inactivated at high H 2 O 2 concentration. Compared to pure hematin, G3.0-He has significantly higher dispersion in acidic and neutral media, and preserves the percentage of survival of fibroblasts over 90%. Notably, G3.0-He possesses an exquisite HRP-mimicking activity in gelation of gelatin derivative with phenolic hydroxyl (tyamine) moieties under mild physiological conditions. The in vitro study demonstrated that Gel-Tyr hydrogel by G3.0-He catalyzed reaction had excellent cytocompatibility and an excellent scaffold for adhesion to fibroblast cells. Therefore, the designed minimalistic G3.0-He catalyst could serve as an effective catalytic alternative for HRP enzyme in the preparation of biomedical hydrogels. • The hematin conjugated G3.0-He was synthesized and characterizated for mimicking HRP enzyme. • The nanosized G3.0-He catalyst performed a highly solubility, stability and cytocompatibility. • The mimetic G3.0-He could be an effective catalytic in preparation of biomedical hydrogel and biochemical analysis. [ABSTRACT FROM AUTHOR]

One candidate for the cytosolic labile iron pool is iron(II)glutathione. There is also a widely held opinion that an equivalent cytosolic labile heme pool exists and that this pool is important for the intracellular transfer of heme. Here we describe a study designed to characterise conjugates that form between heme and glutathione. In contrast to hydrated iron(II), heme reacts with glutathione, under aerobic conditions, to form the stable hematin–glutathione complex, which contains iron(III). Thus, glutathione is clearly not the cytosolic ligand for heme, indeed we demonstrate that the rate of heme degradation is enhanced in the presence of glutathione. We suggest that the concentration of heme in the cytosol is extremely low and that intracellular heme transfer occurs via intracellular membrane structures. Should any heme inadvertently escape into the cytosol, it would be rapidly conjugated to glutathione thereby protecting the cell from the toxic effects of heme. [ABSTRACT FROM AUTHOR]

Pyronaridine (PYR) is an erythrocytic schizonticide with a potent antimalarial activity against multidrug‐resistant Plasmodium. The drug is used in combination with artesunate for the treatment of uncomplicated P. falciparum malaria, in adults and children. The present review briefly retraces the discovery of PYR and recent antimalarial studies which has led to the approval of PYR/artesunate combination (Pyramax) by the European Medicines Agency to treat uncomplicated malaria worldwide. PYR also presents a marked antitumor activity and has revealed efficacy for the treatment of other parasitic diseases (notably Babesia and Trypanosoma infections) and to mitigate the Ebola virus propagation. On the one hand, PYR functions has an inhibitor of hemozoin (biomineral malaria pigment, by‐product of hemoglobin digestion) formation, blocking the biopolymerization of β‐hematin and thus facilitating the accumulation of toxic hematin into the digestive vacuole of the parasite. On the other hand, PYR is a bona fide DNA‐intercalating agent and an inhibitor of DNA topoisomerase 2, leading to DNA damages and cell death. Inhibition of hematin polymerization represents the prime mechanism at the origin of the antimalarial activity, whereas anticancer effects relies essentially on the interference with DNA metabolism, as with structurally related anticancer drugs like amsacrine and quinacrine. In addition, recent studies point to an immune modulatory activity of PYR and the implication of a mitochondrial oxidative pathway. An analogy with the mechanism of action of artemisinin drugs is underlined. In brief, the biological actions of pyronaridine are recapitulated to shed light on the diverse health benefits of this unsung drug. [ABSTRACT FROM AUTHOR]

Plasmodium has evolved to regulate the levels and oxidative states of iron protoporphyrin IX (Fe-PPIX). Antimalarial endoperoxides such as 1,2,4-trioxane artemisinin and 1,2,4-trioxolane arterolane undergo a bioreductive activation step mediated by heme (FeII-PPIX) but not by hematin (FeIII-PPIX), leading to the generation of a radical species. This can alkylate proteins vital for parasite survival and alkylate heme into hematin–drug adducts. Heme alkylation is abundant and accompanied by interconversion from the ferrous to the ferric state, which may induce an imbalance in the iron redox homeostasis. In addition to this, hematin–artemisinin adducts antagonize the spontaneous biomineralization of hematin into hemozoin crystals, differing strikingly from artemisinins, which do not directly suppress hematin biomineralization. These hematin–drug adducts, despite being devoid of the peroxide bond required for radical-induced alkylation, are powerful antiplasmodial agents. This review addresses our current understanding of Fe-PPIX as a bioreductive activator and molecular target. A compelling pharmacological model is that by alkylating heme, endoperoxide drugs can cause an imbalance in the iron homeostasis and that the hematin–drug adducts formed have strong cytocidal effects by possibly reproducing some of the toxifying effects of free Fe-PPIX. The antiplasmodial phenotype and the mode of action of hematin–drug adducts open new possibilities for reconciliating the mechanism of endoperoxide drugs and for malaria intervention.

A brief review is given of theoretical and experimental studies of a series of subnanoscale molecules and clusters performed by the authors with the staff of the Institute of Atomic and Molecular Sciences and the Genomics Center, Academia Sinica (Taipei, Taiwan) using quantum chemical calculations and experimental means of laser spectroscopy and mass spectrometry in gas phase. Several systems are considered: (a) the fragmentation and association of heme, hemin, and beta-hematin; (b) the structure, stability and chirality of the isomers of the protonated octamer of serine; (c) the stability and structure of Li- and Na-substituted saccharides, fullerols, and fullerol-like polyhydroxyl clusters; and (d) the theoretical prediction and experimental synthesis and study of the endohedral methane–fullerene cluster CH4@C60. [ABSTRACT FROM AUTHOR]

Highlights • The ForenSeq kit was used to evaluate the impact of inhibitors on forensic MPS. • Humic acid and hematin were found to mainly affect the initial targeted PCR. • Both inhibitors caused a lowered DNA polymerase activity. • The inhibitor tolerance was improved 5–10 times by adding BSA to PCR1. • PowerPlex Fusion tolerated at least 200 times more inhibitors than the ForenSeq kit. Abstract Massively parallel sequencing holds great promise for new possibilities in the field of forensic genetics, enabling simultaneous analysis of multiple markers as well as offering enhanced short tandem repeat allele resolution. A challenge in forensic DNA analysis is that the samples often contain low amounts of DNA in a background that may interfere with downstream analysis. PCR inhibition mechanisms of some relevant molecules have been studied applying e.g. real-time PCR and digital PCR. However, a detailed understanding of the effects of inhibitory molecules on forensic MPS, including mechanisms and ways to relieve inhibition, is missing. In this study, the effects of two well-characterized PCR inhibitors, humic acid and hematin, have been studied using the ForenSeq DNA Signature Prep kit. Humic acid and hematin resulted in lowered read numbers as well as specific negative effects on certain markers. Quality control of libraries with Fragment analyzer showed that increasing amounts of inhibitors caused a lowered amplicon quantity and that the larger amplicons were more likely to drop out. Further, the inhibitor tolerance could be improved 5–10 times by addition of bovine serum albumin in the initial PCR. On the contrary to the samples with inhibitors, low-template samples resulted in lowered read numbers for all markers. This difference strengthened the conclusion that the inhibitors have a negative effect on the DNA polymerase activity in the initial PCR. Additionally, a common capillary gel electrophoresis-based STR kit was shown to handle at least 200 times more inhibitors than the ForenSeq DNA Signature Prep kit. This suggests that there is room for improvement of the PCR components to ensure analytical success for challenging samples, which is needed for a broad application of MPS for forensic STR analysis. [ABSTRACT FROM AUTHOR]

Abstract Hematin is an oxidized form of heme, and the abnormal levels of hematin in the human body can lead to various inflammatory lesions. Hence, there is still a need to establish a rapid, sensitive and efficient method for hematin detection. Herein, the green fluorescent carbon quantum dots (CQDs) are synthesized by using L-cysteine and hydrogen peroxide as precursors. The synthesized CQDs exhibit some fascinating characters including excellent water solubility, high fluorescence quantum yield, and good stability in a broad pH range of 7.0–11.0 and high ionic strength solution. Excitingly, the fluorescence of CQDs can be rapidly and selectively quenched by hematin via the inner filter effect. Moreover, the detection of hematin by the CQDs fluorescent probe shows a good linearity in the concentration range of 0.5–30 μM with a minimum detection limit of 0.1 μM. Finally, the proposed approach is successfully applied to detect hematin in human blood samples. Graphical Abstract Unlabelled Image Highlights • Green fluorescent CQDs are synthesized using cysteine and H 2 O 2 as precursors. • Active oxygen plays a vital role in the synthesis of strong green fluorescent CQDs. • CQDs fluorescent probe can rapidly, selectively and sensitively respond to hematin. • The method shows potential application for detecting hematin in human blood samples. [ABSTRACT FROM AUTHOR]

Hematin plays a crucial role in various physiological functions, and the determination of hematin in complex biological matrixes is a significant but difficult issue. Considering the unique photophysical/photochemical properties of carbon quantum dots (CQDs) prepared with p-aminobenzoic acid (PABA) and ethanol, a new strategy for the design of fluorescent probes for hematin has been achieved. The proposed sensor array is fabricated based on the inner filter effect (IFE) between hematin and CQDs with phenomenon of selective fluorescence quenching of CQDs which results from the strong absorption of the excitation and emission spectrum of CQDs by hematin. The fluorescence quenching of CQDs is closely related to the amount of hematin and there is a good linear relationship over the range of 0.5–10 μM with a detection limit of 0.25 μM. What's more, the fluorescence assay has been successfully applied for hematin sensing in healthy human red cells showing this sensing assay has a great potential prospect for detection of hematin in the complex matrixes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Kinetic model for catalytic anthraquinone dye decolourization with hematin/H 2 O 2 was validated. • Anthraquinone, hydroxycoumarin, phthalic acid, benzoquinone and benzoic acid were proposed as degradation products. • Dynamic modelling allowed to estimate dye-involved reaction rate constants. • Hematin immobilization promotes pseudo-catalatic pathway. • Dissolved O 2 determinations completed the discussion of undesirable H 2 O 2 dismutation. Hematin-catalysed decolourizations of alizarin red S solutions were carried out in order to validate a peroxidatic model in competition with pseudo-catalatic routes. Absorbance and dissolved oxygen were followed with time and hematin was used in solution or immobilized onto chitosan. Initial rates decreased with increasing dye concentration. Modelled dye concentration profiles properly reproduced experimental data. Optimized rate constants indicated that immobilization reduced hematin activity, emphasized dye inhibition and promoted the pseudo-catalatic pathway. The increase in H 2 O 2 concentration increased oxygen evolution rates whereas the increase of dye concentration depleted them, which agree with the kinetic model proposal. These findings were also discussed considering some additional reactions which consume or evolve oxygen. UV–visible stack spectra of reacting systems allowed to propose some degradation products, whose molecular weights decreased with the increase of hydrogen peroxide to dye molar ratio. This is consistent with accumulation of inorganic radicals proposed by the pseudo-catalatic mechanism. [ABSTRACT FROM AUTHOR]

An electrochemical pre-treatment of a glassy carbon electrode in sodium bicarbonate solution was performed to adsorb hematin (aHtin-GCE), an iron (III) porphyrin present in heme-containing proteins, in order to prepare a new biomimetic sensor for peroxidases. The aHtin-GCe presented peroxidase catalytic activity and a biomimetic behavior related to enzymes responsible for the reduction of H 2 O 2 . The previous glassy carbon surface functionalization in bicarbonate solution also proved to be an essential parameter to be controlled as it provides carboxylic acids terminations, which stabilizes the hematin molecule on the electrode surface. The aHtin-GCE kinetics fitted with the Michaelis–Menten model assume the formation of an enzyme-substrate complex in which H 2 O 2 bonds to the electrochemically reduced iron(II) center with further reduction of the peroxide to peroxyl radical. The observation that lithium ions act as competitive inhibitors toward H 2 O 2 also provided the insight toward the application of the aHtin-GCE as a model dispositive to evaluate peroxidase inhibitors. The aHtin-GCE peak current presented a linear correlation with the concentration of H 2 O 2 from the 400 nM to 800 nM range with an experimental LoD of 0.11 μM. [ABSTRACT FROM AUTHOR]

Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defective, there is an urgent need to develop novel antiplasmodials and antischistosomals. Hemozoin is a disposal product formed from the hemoglobin digestion by some blood-feeding parasites. Hemozoin formation is an essential process for the parasites to detoxify free heme, which is a reliable therapeutic target for identifying novel antiparasitic agents. A series of novel carbazole aminoalcohols were designed and synthesized as potential antiplasmodial and antischistosomal agents, and several compounds showed potent in vitro activities against Plasmodium falciparum 3D7 and Dd2 strains and adult and juvenile Schistosoma japonicum . Investigations on the dual antiparasitic mechanisms showed the correlation between inhibitory activity of β -hematin formation and antiparasitic activity. Inhibiting hemozoin formation was identified as one of the mechanisms of action of carbazole aminoalcohols. Compound 7 displayed potent antiplasmodial ( Pf 3D7 IC 50 = 0.248 μM, Pf Dd2 IC 50 = 0.091 μM) and antischistosomal activities (100% mortality of adult and juvenile schistosomes at 5 and 10 μg/mL, respectively) and exhibited low cytotoxicity (CC 50 = 7.931 μM), which could be considered as a promising lead for further investigation. Stoichiometry determination and molecular docking studies were also performed to explain the mode of action of compound 7 . [ABSTRACT FROM AUTHOR]

A mathematical description of the kinetics of the hematin catalysed decolourization reaction of Orange II alkaline solutions was constructed and validated under the assumption that hematin mimics the action of peroxidases. The clean oxidant H 2 O 2 was applied, however, hematin dismutated it, as catalases do, under reaction conditions. Thus, special attention was cared to the understanding of this ineffective side-reaction by the proposal of straightforward pathways concerning the catalatic or the pseudo-catalatic cycles. Model validations were implemented by a parametrization procedure of relevant rate constants under dynamic simulation fitting to selected experimental time-courses data. The peroxidatic coupled to pseudo-catalatic mechanism gave predictions closer to experimental findings in a wide range of conditions. The initial rate method for data processing was successfully applied for providing reliable initial rate constant guesses but also for the detection of unexpected rate depletion at high dye concentrations. This was considered in the model as unproductive dye coordination to hematin native state prior to H 2 O 2 activation. The pseudo-catalatic pathway involves the production of superoxide and its coordination to hematin native state to afford inactive but regenerable ferrous porphyrin. Model underestimations of experimental data were interpreted as cooperative oxidation of Orange II molecules by superoxide whereas model deviations at high dye concentration (>400 mg/l) was assigned to further hematin catalysed oxidation of Orange II degraded products. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOF) are promising candidates for the construction of artificial nanozymes and have found applications in many fields. However, the preparation of nanosized MOF materials with high performance and good dispersibility is still a big challenge and is in great demand as signal labels for immunoassays. In this work, hierarchically structured and highly dispersible MOF nanoparticles were facilely prepared in a one-pot method. Self-assembled micelles from PEGylated hematin were used as structured templates to mediate the formation of zeolitic imidazole framework-8 (ZIF-8) nanoparticles in aqueous solution. The encapsulation of micelles in ZIF-8 frameworks produces well-dispersed nanoparticles and generates dual-confinement effects for catalytic hematin. Owing to the hierarchical structures, the formed MOF nanozymes show enhanced peroxidase-like activity and enable persistent chemiluminescence behaviors for the luminol system. Sandwich-type chemiluminescence immunoassays for carcinoembryonic antigen (CEA) were proposed using MOF nanozymes as signal labels, and good analytical performances were achieved. The combination of self-assembly and biomineralization may open new avenues for the development of MOF nanomaterials.

Acidic lipid extracts from mouse liver, kidney, heart, brain, and lung inhibited human pseudoheterodimeric adenylyl cyclases (hACs) expressed in HEK293 cells. Using an acidic lipid extract from bovine lung, a combined MS- and bioassay-guided fractionation identified heme b as inhibitor of membrane-bound ACs. IC 50 concentrations were 8–12 μM for the hAC isoforms. Hemopexin and bacterial hemophore attenuated heme b inhibition of hAC5. Structurally related compounds, such as hematin, protoporphyrin IX, and biliverdin, were significantly less effective. Monomeric bacterial class III ACs (mycobacterial ACs Rv1625c; Rv3645; Rv1264; cyanobacterial AC CyaG) were inhibited by heme b with similar efficiency. Surprisingly, structurally related chlorophyll a similarly inhibited hAC5. Heme b inhibited isoproterenol-stimulated cAMP accumulation in HEK293 cells. Using cortical membranes from mouse brain hemin efficiently and reversibly inhibited basal and Gsα-stimulated AC activity. The physiological relevance of heme b inhibition of the cAMP generating system in certain pathologies is discussed. • Acidic lipid extracts from mouse tissues inhibited human adenylyl cyclases. • From an acidic lipid extract (lung) a MS- and bioassay-guided fractionation identified heme b as inhibitor. IC 50 concentrations were 8–12 μM for all isoforms. • Hemopexin and bacterial hemophore attenuated heme b inhibition. • Structurally related compounds, e.g., hematin, protoporphyrin IX, and biliverdin, were less effective. • Bacterial class III ACs were inhibited similarly. • Surprisingly, chlorophyll a similarly inhibited hAC5. Heme b inhibited isoproterenol-stimulated cAMP in HEK293 cells and cortical membranes from mouse brain. • The physiological relevance of heme b inhibition of the cAMP generating system in certain pathologies is discussed. [ABSTRACT FROM AUTHOR]

Dermanyssus gallinae , also known as the poultry red mite (PRM), is one of widespread ectoparasite in the poultry industry worldwide, causing direct and indirect detriments to poultry as well as substantial financial losses. Novel control methods are urgently needed to improve the current acaricide-based control of D. gallinae. The control approach based on arrestment pheromone is environment-friendly but the related research is limited in PRMs. In the present study we found two compounds from the mite feces acting as arrestment pheromones of D. gallinae , which could lead to mite arrestment upon contact. One is guanine, which was also found in unfed female mites' acid-saline extract. The other is hematin. Moreover, it was found that the ferric ion of hematin played a pivotal role in stimulating the arrestment of mites. Finally, it was found the combination of guanine or/and hematin plus cypermethrin led to significantly improved mite-killing performance compared with cypermethrin, showing a promising potential of novel control method based on the arrestment pheromone. • Guanine and hematin are arrestment pheromones of mites. • Ferric ion of hematin plays a key role in stimulating the arrestment of mites. • Adding arrestment pheromones to acaricide improves mite-killing performance. [ABSTRACT FROM AUTHOR]

Two combinations of assembly pheromone (AP), with and without hematin were utilized as a lure for the unfed larvae, nymph and adults of Rhipicephalus sanguineus ticks. In-vitro trials were carried out with the AP encapsulated in calcium alginate beads and the response of different stages of ticks were recorded. Analysis of results revealed that rapid attraction was evident in unfed larvae exposed to beads containing AP without hematin. In case of unfed nymphal and adult stages, the presence or absence of hematin did not have any impact on arrestment. [ABSTRACT FROM AUTHOR]

During malarial anemia, 20 uninfected red blood cells (RBCs) are destroyed for every RBC infected by Plasmodium falciparum (Pf). Increasing evidence indicates an important role for complement in destruction of uninfected RBCs. Products of RBC lysis induced by Pf, including the digestive vacuole and hematin, activate complement and promote C3 fragment deposition on uninfected RBCs. C3-opsonized cells are then subject to extravascular destruction mediated by fixed tissue macrophages which express receptors for C3 fragments. The Compstatin family of cyclic peptides blocks complement activation at the C3 cleavage step, and is under investigation for treatment of complement-mediated diseases. We demonstrate, that under a variety of stringent conditions, second-generation Compstatin analogue Cp40 completely blocks hematin-mediated deposition of C3 fragments on naïve RBCs. Our findings indicate that prophylactic provision of Compstatin for malaria-infected individuals at increased risk for anemia may provide a safe and inexpensive treatment to prevent or substantially reduce malarial anemia. [ABSTRACT FROM AUTHOR]

Background Haem, an essential cofactor in aerobic organisms, can cause oxidative stress and impose toxic effects on tissues and organs. It can induce aggregation of proteins via dityrosine cross-linking and cause neurodegenerative diseases. Although dityrosine cross-linking in many proteins induced by haem has been reported, not all the proteins have the same effect or the efficiency of cross-linking varies, while the reason has not been clarified. Methods The correlation of protein structure/conformation with its aggregation tendency via dityrosine induced by hematin (oxidized form of haem) in the presence of hydrogen peroxide (H 2 O 2 ) was studied through reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fluorescence and circular dichroism (CD) measurements, and the mechanism was investigated by performing UV–Vis absorbance, Raman spectroscopy and low-temperature electron spin resonance (ESR) experiments. Results It was found that proteins in unstructured state are more readily to be cross-linked via dityrosine formation by hematin-H 2 O 2 . The unstructured protein without steric effect can coordinate with hematin to form six-coordinated protein-hematin complex, in which the produced tyrosyl radicals by H 2 O 2 are with high tendency to dimerize to form dityrosine. Conclusions Our results demonstrate that protein structure/conformation can affect its coordination state with haem, and the tendency of reaction of two tyrosyl radicals, further influencing the yield and efficiency of dityrosine cross-linking in the presence of H 2 O 2 . General significance This research can help to deepen our understanding of the protein aggregation and inactivation mechanisms in varied sophisticated conditions, and especially give us the new insight into the toxic effects under haem stress. [ABSTRACT FROM AUTHOR]

Targeted nanomedicine for cancer therapy has gained widespread popularity and is being extensively explored. Porphyrins have intrinsic tumor localizing ability and have been studied for photodynamic therapy. However, they have not been used as cancer targeting agents for nanomedicines. In this study, PLGA nanoparticles were formulated and an iron-containing blood porphyrin, hematin was conjugated to the surface of the nanoparticles to investigate selectivity towards cancer cell and cellular internalization. Hematin was previously shown to facilitate growth and proliferation of cancer cells. PLGA nanoparticles were characterized by FE-SEM, AFM, DLS, and Zeta potential analyzer. The conjugation of hematin was confirmed by FTIR. HeLa cells were used to study tumor selectivity and uptake. Hematin conjugated particles (ζ potential: − 15.19 mV) showed higher affinity towards the cancer cells than the control particles. The result indicated that the particles were internalized by heme carrier protein-1. Together these data suggest that hematin is a promising cancer targeting material for nanotherapeutics. [ABSTRACT FROM AUTHOR]

Catalysts supported on nanomaterials have been widely investigated for the treatment of hazardous materials. This work has developed a novel method for grafting hematin on nanomaterials for catalyzing the oxidation of aniline in order to remove aniline from wastewater. Magnetic multi-walled carbon nanotubes (M-MWCNTs) were coated with a layer formed through the hydrolysis and condensation of 3-mercaptopropyltriethoxysilane (MPTS). Hematin was specifically grafted on the MPTS-coated M-MWCNTs through thiol-alkene reaction. Hematin-MPTS-M-MWCNTs were used to catalyze the oxidation of aniline, and a high efficiency has been obtained. Consecutive use of the conjugate of hematin-MPTS-M-MWCNTs has been investigated, and the activity has been retained to a significant extent after five reaction/cleaning cycles. The result demonstrates that hematin-MPTS-M-MWCNTs are efficient for catalyzing the oxidation of aniline. The methodology for the specific grafting of hematin is of general utility, it is an easy-to-operate method and can be extended to other supports. Potentially, hematin-MPTS-based conjugates have a widespread application in catalyzing the removal of aniline from wastewater. [ABSTRACT FROM AUTHOR]

The role of monoxide hemoglobin (COHb) in improvement of chicken sausage color was investigated. COHb and NaNO synergistically increased a* values. Addition of 0.1% COHb decreased the residual nitrite content in the presence of 0.001% NaNO. Compared with controls, the combined treatment resulted in significantly higher nitroso pigment contents while the single treatment resulted in slightly higher nitroso pigment contents. Visible spectrometry indicated that both nitrosohemochrome (NH) and hematin were the main ingredients of pigments extracted from chicken sausage treated with a combination of 0.006% NaNO and 0.6% COHb. Formation of NH and hematin caused an increase in a* values and a decrease in L* values, respectively. COHb showed potential for use in meat product formulations. [ABSTRACT FROM AUTHOR]

Pooled Immunoglobulin G (IgG), hematin and the membrane-disruptive amphipathic peptide melittin have received attention as powerful biomacromolecules for biomedical and pharmacology applications. Their action on surface properties, oxidation status and epifluorescence properties measured in vitro provide useful information about the functional activity of upper biomacromolecules in erythrocytes in vivo. The hemolysis of erythrocyte membranes, as well as changes in hematocrit and the morphology of erythrocytes, was investigated here via fluorescence microscopy using FITC-concanavalin A binding to cells. The effect of melittin on the membrane capacitance and resistance of model lipid bilayers was probed via electrochemical impedance spectroscopy. Lipid bilayer capacitance was higher in the presence of 0.10 g/L melittin compared to that in the control, which is likely related to bilayer thinning and alterations of the dielectric permittivity of melittin-treated membranes. The biomolecule interactions with red blood cells were probed in physiological media in which the surface of erythrocyte membranes was negatively charged. Surface parameters of erythrocytes are reported upon IgG/hematin and IgG/melittin treatment. Pooled IgG in the presence of melittin, preincubated IgG/hematin preparations promoted a significant decrease in the electrokinetic potential of erythrocytes (Rh-positive). A malondialdehyde (MDA) assay revealed a high rate of lipid peroxidation in erythrocytes treated with IgG/hematin or IgG/melittin preparations. This finding might be a result of pooled IgG interactions with the hematin molecule and the subsequent conformational changes in the protein molecule altering the electrokinetic properties of the erythrocyte membrane related to the Rh group type of erythrocytes. The pooled IgG and hematin are reported to have important consequences for the biophysical understanding of the immunopathological mechanisms of inflammatory, autoimmune and antibody-mediated pathological processes.

Malaria is an infectious disease caused by Plasmodium type parasites transmitted by the bites of infected female anopheles mosquitoes. The malaria parasite multiplies in red blood cells where it degrades hemoglobin. This degradation of hemoglobin proteins releases hematin, an iron-containing porphyrin, which provokes membrane disruption and lysis. The malaria parasite blocks hematin-induced lysis by biocrystallization, a process that converts hematin into insoluble and chemically inert crystals. Hematin molecules are especially prone to self-assembly as dimers, oligomers and aggregates depending on environmental conditions (pH, solvent, temperature, concentration, ionic strength). Considering the different forms of hematin-based assemblies, it is still unclear which are the ones able to interact with membranes. We have prepared hematin under different conditions to form hematin-based assemblies and to measure their ability to interact and to disorganize membranes. Our results show that different forms of hematin molecules are able to penetrate lipid membranes. Interestingly, this membrane activity is spontaneously inhibited at acidic pH and it can be restored under neutral pH. By contrast, the oligomers of β-hematin were found to be completely harmless toward lipid membranes. Finally, the AFM visualization of hematin interaction with supported lipid bilayers showed for the first time its preferential interaction with defaults in membranes, at the boundaries between two distinct lipid phases. The superficial adsorption of aggregates on membranes and the absence of effect due to oligomers were also confirmed with AFM. [ABSTRACT FROM AUTHOR]

A new proposal for designing sensitive photoeletrochemical sensor with a ternary hybrid film developed by absorbing hematin on carbon nanohorns superstructures and poly- l -lysine complex support to achieve quantificational detection of 4-hydrox-3-nitrobenzenenearsonic acid (HNBAA) was offered. Here, hematin with easy acquirement, good biocompatibility and strong visible light harvesting capability, was introduced as photosensitizer for photoelectrochemical determination. Additionally, the complex support composed by fascicled superstructures of carbon nanohorns which possessed many superiors, such as excellent electronic conductivity, large specific area and adsorption etc., and poly- l -lysine which could form hydrogen bond with hematin performed excellent immobilization action of hematin. Due to the synergistic effect and surface enhancement effect, complex support provided a charge-transfer matrix to catch and transport excited electron from hematin rapidly, which was benefit to baffle photogenerated electron–hole recombination and improve photoelectrochemical signal in visible light region effectively. HNBAA, as a photogenerated hole scavenger, enhanced the photoelectrochemical response again. Furthermore, the excellent sensitivity and broad linear detection range to HNBAA of this sensor with good stability and high selectivity, satisfied reproducibility and acceptable accuracy was propitious to practical application of sample analysis, and the good biocompatibility of modified materials and low applied potential on this sensor laid a foundation for its promising application. [ABSTRACT FROM AUTHOR]

In this work, we presented a novel signal amplification approach to construct an electrochemical DNA biosensor for the ultrasensitive determination of sequence-specific DNA by exploiting hematin as biomimetic catalyst toward in situ metallization. Briefly, thiolated peptide nucleic acid (PNA) probes were firstly immobilized onto gold electrode through the formation of self-assembled monolayer (SAM) and then hybridization was accomplished in the ensuing step. After that, hematin molecules were introduced to the hybridized PNA/DNA heteroduplexes by employing phosphate–zirconium–carboxylate coordination chemistry. Next, the attached hematin molecules acted as catalyst in accelerating the reduction of silver ions in the presence of catechol, leading to the in situ deposition of silver particles onto the electrode. Finally, the deposited silver particles were electrochemically stripped into KCl solution and measured by square wave voltammetry (SWV). Under optimal conditions, the hematin-based electrochemical DNA biosensor presented a good linear relationship between the stripping peak currents and logarithm of single-stranded DNA (ssDNA) concentrations in the range from 0.1 fM to 0.1 nM with a low detection limit of 62.41 aM, and it rendered satisfactory analytical performance for the determination of ssDNA in serum samples. Furthermore, it exhibited good reproducibility and stability, meanwhile, it also showed excellent specificity toward single-nucleotide polymorphism (SNP). Therefore, the hematin-based signal amplification approach has great potential in clinical applications and is also suitable for quantification of biomarkers at ultralow level. [ABSTRACT FROM AUTHOR]