Development of an enzyme-linked immunosorbent assay for newborns dried blood spot thyroglobulin.

Background: Thyroglobulin (Tg) is a biomarker of iodine status. Newborn Tg is a more sensitive marker than neonatal TSH in detecting variations in iodine intake. This study aims to validate an enzyme-linked immunosorbent assay (ELISA) for Tg determination on dried blood spots (DBS) in newborns.

Thyrotropin Screening of Newborns: Before or After 72 Hours of Life? Before Discharge or at Home?

Until November 2019 in Belgium, dried blood spot (DBS) sampling was performed between 72 and 120 hours of life, when a majority of newborns had already been discharged from the maternity. In November 2019, the policy for newborn screening in South Belgium changed to allow sampling as soon as 48 hours of life, with the objective to accelerate the process and to allow more sampling during the hospital stay. Our objective was to evaluate the impact of this policy modification and, in particular, to assess the effectiveness of screening for hypothyroidism based on sampling before or after 72 hours of life, as well as to compare the effectiveness of DBS collection before discharge or at home.

Hereditary Tyrosinemia Type 1 Mice under Continuous Nitisinone Treatment Display Remnants of an Uncorrected Liver Disease Phenotype.

Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates. If left untreated, they experience hepatic failure with comorbidities involving the renal and neurological system and the development of hepatocellular carcinoma (HCC).

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries.

A Water Molecule Triggers Guest Exchange at a Mono-Zinc Centre Confined in a Biomimetic Calixarene Pocket: A Model for Understanding Ligand Stability in Zn Proteins.

Invited for the cover of this issue are Kristin Bartik, Olivia Reinaud and co-workers at the Université libre de Bruxelles and Université Paris Descartes. The image depicts a Zn protein and highlights the role that a single water molecule can play in catalysing ligand exchange. Read the full text of the article at 10.

A Water Molecule Triggers Guest Exchange at a Mono-Zinc Centre Confined in a Biomimetic Calixarene Pocket: a Model for Understanding Ligand Stability in Zn Proteins.

In this study, the ligand exchange mechanism at a biomimetic Zn centre, embedded in a pocket mimicking the possible constrains induced by a proteic structure, is explored. The residence time of different guest ligands (dimethylformamide, acetonitrile and ethanol) inside the cavity of a calix[6]arene-based tris(imidazole) tetrahedral zinc complex was probed using 1D EXchange SpectroscopY NMR experiments. A strong dependence of residence time on water content was observed with no exchange occurring under anhydrous conditions, even in the presence of a large excess of guest ligand.

Oxidative Stress, Glutathione Metabolism, and Liver Regeneration Pathways Are Activated in Hereditary Tyrosinemia Type 1 Mice upon Short-Term Nitisinone Discontinuation.

Hereditary tyrosinemia type 1 (HT1) is an inherited condition in which the body is unable to break down the amino acid tyrosine due to mutations in the fumarylacetoacetate hydrolase (FAH) gene, coding for the final enzyme of the tyrosine degradation pathway. As a consequence, HT1 patients accumulate toxic tyrosine derivatives causing severe liver damage. Since its introduction, the drug nitisinone (NTBC) has offered a life-saving treatment that inhibits the upstream enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), thereby preventing production of downstream toxic metabolites.

Towards the Development of Photo-Reactive Ruthenium(II) Complexes Targeting Telomeric G-Quadruplex DNA.

The design and characterization of new ruthenium(II) complexes aimed at targeting G-quadruplex DNA is reported. Importantly, these complexes are based on oxidizing 1,4,5,8-tetraazaphenanthrene (TAP) ancillary ligands known to favour photo-induced electron transfer (PET) with DNA. The photochemistry of complexes 1-4 has been studied by classical methods, which revealed two of them to be capable of photo-abstracting an electron from guanine.

Submerging a Biomimetic Metallo-Receptor in Water for Molecular Recognition: Micellar Incorporation or Water Solubilization? A Case Study.

Molecular recognition in water is an important topic, but a challenging task due to the very competitive nature of the medium. The focus of this study is the comparison of two different strategies for the water solubilization of a biomimetic metallo-receptor based on a poly(imidazole) resorcinarene core. The first relies on a new synthetic path for the introduction of hydrophilic substituents on the receptor, at a remote distance from the coordination site.

Ultrafast charge transfer excited state dynamics in trifluoromethyl-substituted iridium(iii) complexes.

Time-resolved spectroscopy was exploited to gain new insights into the nature and dynamics of charge transfer excited states of bis-cyclometalated Ir(iii) complexes. We showed that its dynamics is strongly influenced by the nature of the diimine ligand due to the existence of a ligand-ligand charge transfer process in the picosecond timescale. All the results are supported by DFT/TD-DFT calculations and spectroelectrochemistry.

Synthesis and photophysical studies of a multivalent photoreactive Ru-calix[4]arene complex bearing RGD-containing cyclopentapeptides.

Photoactive ruthenium-based complexes are actively studied for their biological applications as potential theragnostic agents against cancer. One major issue of these inorganic complexes is to penetrate inside cells in order to fulfil their function, either sensing the internal cell environment or exert a photocytotoxic activity. The use of lipophilic ligands allows the corresponding ruthenium complexes to passively diffuse inside cells but limits their structural and photophysical properties.

Ter-Ionic Complex that Forms a Bond Upon Visible Light Absorption.

A "ter-ionic complex" composed of a tetracationic Ru(II) complex and two iodide ions was found to yield a covalent I-I bond upon visible light excitation in acetone solution. H NMR, visible absorption and DFT studies revealed that one iodide was associated with a ligand while the other was closer to the Ru metal center. Standard Stern-Volmer quenching of the excited state by iodide revealed upward curvature with a novel saturation at high concentrations.

Converging Energy Transfer in Polynuclear Ru(II) Multiterpyridine Complexes: Significant Enhancement of Luminescent Properties.

Ruthenium-based complexes are widely used as photocatalysts, as photosensitizers, or as building blocks for supramolecular assemblies. In the field of solar energy conversion, building light harvesting antenna is of prime interest. Nevertheless, collecting light is mandatory but not sufficient; once collected and transferred, the exciton has to be long-lived enough to be transferred to a catalytic site.

Trifluoromethyl-Substituted Iridium(III) Complexes: From Photophysics to Photooxidation of a Biological Target.

Photodynamic therapeutic agents are of key interest in developing new strategies to develop more specific and efficient anticancer treatments. In comparison to classical chemotherapeutic agents, the activity of photodynamic therapeutic compounds can be finely controlled thanks to the light triggering of their photoreactivity. The development of type I photosensitizing agents, which do not rely on the production of ROS, is highly desirable.

Selective recognition of quaternary ammonium ions and zwitterions by using a biomimetic bis-calix[6]arene-based receptor.

Artificial receptors able to recognize efficiently chemical species bearing a quaternary ammonium group have potential applications in the fields of biological and environmental analyses. A possible biomimetic strategy for the elaboration of such receptors consists of associating in close proximity a polyaromatic cavity with a polar binding site. Herein, we show that bis-calix[6]arene 1 behaves as a heteroditopic receptor that can bind biologically relevant quaternary ammonium ions and zwitterions.

A Ruthenium(II) Complex as a Luminescent Probe for DNA Mismatches and Abasic Sites.

[Ru(bpy)(BNIQ)] (BNIQ = Benzo[c][1,7]naphthyridine-1-isoquinoline), which incorporates the sterically expansive BNIQ ligand, is a highly selective luminescent probe for DNA mismatches and abasic sites, possessing a 500-fold higher binding affinity toward these destabilized regions relative to well-matched base pairs. As a result of this higher binding affinity, the complex exhibits an enhanced steady-state emission in the presence of DNA duplexes containing a single base mismatch or abasic site compared to fully well-matched DNA. Luminescence quenching experiments with Cu(phen) and [Fe(CN)] implicate binding of the complex to a mismatch from the minor groove via metalloinsertion.

New Ruthenium-Based Probes for Selective G-Quadruplex Targeting.

Telomeric regions containing G-quadruplex (G4) structures play a pivotal role in the development of cancers. The development of specific binders for G4s is thus of great interest in order to gain a deeper understanding of the role of these structures, and to ultimately develop new anticancer drug candidates. For several years, Ru complexes have been studied as efficient probes for DNA.

Photochemistry of ruthenium(ii) complexes based on 1,4,5,8-tetraazaphenanthrene and 2,2'-bipyrazine: a comprehensive experimental and theoretical study.

Polyazaaromatic ruthenium(ii) complexes have been largely studied over the last decades, particularly in the scope of the biological applications, for the development of new diagnostic and phototherapeutic agents. In this context, Ru(ii) complexes able to react with biomolecules upon excitation are of great interest. Photo-oxidizing Ru(ii) complexes based on π-deficient ligands, such as bpz (2,2'-bypyrazine) and TAP (1,4,5,8-tetraazaphenathrene), were designed to allow a photo-induced electron transfer (PET) to take place in presence of biomolecules, thanks to their highly photo-oxidizing MLCT state.

Photocontrolled Supramolecular Assembling of Azobenzene-Based Biscalix[4]arenes upon Starting and Stopping Laser Trapping.

Laser trapping in chemistry covers various studies ranging from single molecules, nanoparticles, and quantum dots to crystallization and liquid-liquid phase separation of amino acids. In this work, a supramolecular assembly of azobenzene-based biscalix[4]arene is generated in ethyl acetate using laser trapping; its nucleation and growth are elucidated. No trapping behavior was observed when a 1064 nm laser beam was focused inside of the solution; however, interesting assembling phenomena were induced when it was shined at the air/solution interface.

A nano-sized container for specific encapsulation of isolated water molecules.

A calix[4]arene-based molecular box was synthesized. Its properties were characterized through XRD and extensive NMR studies. This receptor is able to encapsulate specifically two isolated water molecules in both non-protic and protic solvents.

[Ru(Me4phen)2dppz](2+), a Light Switch for DNA Mismatches.

[Ru(Me4phen)2dppz](2+) serves as a luminescent "light switch" for single base mismatches in DNA. The preferential luminescence enhancement observed with mismatches results from two factors: (i) the complex possesses a 26-fold higher binding affinity toward the mismatch compared to well-matched base pairs, and (ii) the excited state emission lifetime of the ruthenium bound to the DNA mismatch is 160 ns versus 35 ns when bound to a matched site. Results indicate that the complex binds to the mismatch through a metalloinsertion binding mode.

Photoaddition of two guanine bases to single Ru-TAP complexes. Computational studies and ultrafast spectroscopies to elucidate the pH dependence of primary processes.

The covalent photoadduct (PA) between [Ru(TAP)3](2+) (TAP = 1,4,5,8-tetraazaphenanthrene) and guanosine monophosphate (GMP) opened the way to interesting photobiological applications. In this context, the PA's capability upon illumination to give rise to the addition of a second guanine base is especially interesting. The origins of these intriguing properties are for the first time thoroughly investigated by an experimental and theoretical approach.

Revisited photophysics and photochemistry of a Ru-TAP complex using chloride ions and a calix[6]crypturea.

The effects of the nonprotonated and protonated calix[6]crypturea 1/1(•)H(+) on the PF6(-) and Cl(-) salts of a luminescent Ru-TAP complex (TAP = 1,4,5,8-tetraazaphenanthrene) were investigated. Thus, the phototriggered basic properties of this complex were examined with 1(•)H(+) in acetonitrile (MeCN) and butyronitrile (BuCN). The Ru excited complex was shown to be able to extract a proton from the protonated calixarene, accompanied by a luminescence quenching in both solvents.