NIR-emission from Yb(III)- and Nd(III)-based complexes in the solid state sensitized by a ligand system absorbing in a broad UV and visible spectral window

In this contribution, we present the synthesis, characterization and spectroscopic investigation of the heteroleptic (R,R)-YbL1(tta) and (R,R)-NdL1(tta) complexes (with tta = 2-thenoyltrifluoroacetonate and L1 = N,N'-bis(2-(8-hydroxyquinolinate)methylidene)-1,2-(R,R or S,S)-cyclohexanediamine) in the solid state. The f-f metal-centered NIR luminescence emission of Nd(III) and Yb(III) is efficiently sensitized by both chromophoric ligands in a very broad range of wavelengths [from 250 to 600 nm, in the case of Nd(III) and from 250 to 650 nm, for Yb(III)]. A possible energy transfer mechanism is proposed: for (R,R)-NdL1(tta) complex a classical Ligand-to-Metal Energy Transfer (LMET) mechanism (antenna effect) is suggested, whilst in the case of the (R,R)-YbL1(tta) complex, the presence of a ligand-to-metal charge transfer (LMCT) state determines the sensitization of Yb(III) luminescence. We propose that this level is populated by the singlet and triplet excited states belonging to pi -> pi* and n -> pi* transitions of both ligands and it can transfer the excitation energy to F-2(5/2)

Circularly Polarized Luminescence from New Heteroleptic Eu(III) and Tb(III) Complexes

The complexes [Eu(bpcd)(tta)], [Eu(bpcd)(Coum)], and [Tb(bpcd)(Coum)] [tta = 2-thenoyltrifluoroacetyl-acetonate, Coum = 3-acetyl-4-hydroxy-coumarin, and bpcd = N,N′-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane-N,N′-diacetate] have been synthesized and characterized from photophysical and thermodynamic points of view. The optical and chiroptical properties of these complexes, such as the total luminescence, decay curves of the Ln(III) luminescence, electronic circular dichroism, and circularly polarized luminescence, have been investigated. Interestingly, the number of coordinated solvent (methanol) molecules is sensitive to the nature of the metal ion. This number, estimated by spectroscopy, is >1 for Eu(III)-based complexes and <1 for Tb(III)-based complexes. A possible explanation for this behavior is provided via the study of the minimum energy structure obtained by density functional theory (DFT) calculations on the model complexes of the diamagnetic Y(III) and La(III) counterparts [Y(bpcd)(tta)], [Y(bpcd)(Coum)], and [La(bpcd)(Coum)]. By time-dependent DFT calculations, estimation of donor-acceptor (D-A) distances and of the energy position of the S1and T1ligand excited states involved in the antenna effect was possible. These data are useful for rationalizing the different sensitization efficiencies (ηsens) of the antennae toward Eu(III) and Tb(III). The tta ligand is an optimal antenna for sensitizing Eu(III) luminescence, while the Coum ligand sensitizes better Tb(III) luminescence {φovl= 55%; ηsens≥ 55% for the [Tb(bpcd)(Coum)] complex}. Finally, for the [Eu(bpcd)(tta)] complex, a sizable value of glum(0.26) and a good quantum yield (26%) were measured

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley &amp; Sons Ltd on behalf of European Academy of Neurology.Background and purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort. Methods: The study employed two distinct methods. MDC was calculated using distribution-based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor-based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12-month HFMSE could be anchored to a caregiver-reported clinical perception questionnaire. Results: With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of −2 for type II and −4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and −3.2 for deterioration. Furthermore, distribution-based methods uncovered varying values across age and functional status subgroups within each SMA type. Conclusions: These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies

Different trajectories in upper limb and gross motor function in spinal muscular atrophy

INTRODUCTION: The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) have been widely used in natural history studies and clinical trials. Our aim was to establish how the scales relate to each other at different age points in spinal muscular atrophy (SMA) type 2 and 3, and to describe their coherence over 12 mo. METHODS: The study was performed by cross-sectional and longitudinal reanalysis of previously published natural history data. The longitudinal analysis of the 12-mo changes also included the analysis of concordance between scales with changes grouped as stable (±2 points), improved (>+2) or declined (>−2). RESULTS: Three hundred sixty-four patients were included in the cross-sectional analysis, showing different trends in score and point of slope change for the two scales. For type 2, the point of slope change was 4.1 y for the HFMSE and 5.8 for the RULM, while for type 3, it was 6 y for the HFMSE and 7.3 for the RULM. One-hundred-twenty-one patients had at least two assessments at 12 mo. Full concordance was found in 57.3% of the assessments, and in 40.4% one scale remained stable and the other changed. Each scale appeared to be more sensitive to specific age or functional subgroups. DISCUSSION: The two scales, when used in combination, may increase the sensitivity to detect clinically meaningful changes in motor function in patients with SMA types 2 and 3

NIR-emission from Yb(III)- and Nd(III)-based complexes in the solid state sensitized by a ligand system absorbing in a broad UV and visible spectral window

In this contribution, we present the synthesis, characterization and spectroscopic investigation of the heteroleptic (R,R)-YbL1(tta) and (R,R)-NdL1(tta) complexes (with tta = 2-thenoyltrifluoroacetonate and L1 = N,N′-bis(2-(8-hydroxyquinolinate)methylidene)-1,2-(R,R or S,S)-cyclohexanediamine) in the solid state. The f-f metal-centered NIR luminescence emission of Nd(III) and Yb(III) is efficiently sensitized by both chromophoric ligands in a very broad range of wavelengths [from 250 to 600 nm, in the case of Nd(III) and from 250 to 650 nm, for Yb(III)]. A possible energy transfer mechanism is proposed: for (R,R)-NdL1(tta) complex a classical Ligand-to-Metal Energy Transfer (LMET) mechanism (antenna effect) is suggested, whilst in the case of the (R,R)-YbL1(tta) complex, the presence of a ligand-to-metal charge transfer (LMCT) state determines the sensitization of Yb(III) luminescence. We propose that this level is populated by the singlet and triplet excited states belonging to π → π * and n → π * transitions of both ligands and it can transfer the excitation energy to 2F5/2

Nanodiamonds coupled with plant bioactive metabolites: A nanotech approach for cancer therapy

Nanodiamond application in biotechnological and medical fields is nowadays in continuous progress. In fact, biocompatibility, reduced dimensions and high surface chemical interaction are specific features that make nanodiamonds perfect intracellular carriers of bioactive compounds. By confocal microscopy, we confirmed that nanodiamonds were able to penetrate in cell cytoplasm but we also demonstrated how they remained embedded in nuclear membrane just exposing some little portions into nuclear area, definitively clarifying this topic. In this work, for the first time, nanodiamonds were conjugated with plant secondary metabolites, ciproten and quercetin. Moreover, since drug-loading on nanoparticles was strongly conditioned by their chemical surface, different types of nanodiamonds (oxidized, wet chemical reduced and plasma reduced) were synthesized in this work and then functionalized with plant compounds. We found that ciproten and quercetin antiproliferative effects, on human (HeLa) and murine (B16F10) tumor cells, were improved after nanodiamond conjugation. Moreover, plant molecules highly reduced their in vitro pro-oxidant, cytotoxic and pro-apoptotic activity when associated with nanodiamond. We are led to suppose that natural drug-nanodiamond adducts would act at cellular level by different molecular mechanisms with respect to plant metabolite pure forms. Finally, our results showed that chemical and structural modifications of nanodiamond surfaces influenced the bioactivity of transported drugs. According to all these evidences, this work can be considered as a promotional research to favor the use of bioactive plant molecules associated with nanodiamonds for therapeutic purposes

Plasmatic exosome number and size distinguish prostate cancer patients from healthy individuals: a prospective clinical study

There is a urgent need for valuable strategy in early and less invasive diagnosis for cancer. Preliminary data have shown that the plasmatic levels of exosomes increase in cancer condition. This study investigates the relevance of plasmatic levels and size distribution of exosomes in 42 individuals with no signs of urological disease (CTR) as compared to 65 prostate cancer patients (PCa). It was used Nanoparticle Tracking Analysis (NTA), a highly reliable and sensitive method for exosomes characterization and quantification. The relation structure among the NTA-derived parameters was assessed by means of Principal Component Analysis, which allowed detecting the global discriminant power of NTA test in terms of Receiver Operating Characteristic (ROC) curve and the selection of cut-off thresholds. The results showed that PCa had significantly higher plasmatic levels of exosomes and that the exosomes were smaller in size as compared to the CTR; the values reached 89% sensitivity and 71% specificity, in distinguishing PCa from CTR. These results propose a new exosome-based non-invasive clinical approach for the clinical follow-up of prostate cancer undergoing surgical treatment; in addition this method may be developed as a new screening test for prostate cancer’s early diagnosis. While this clinical study was performed in prostate cancer, it may represent a proof of concept extendable to virtually all cancers, as it is suggested by both pre-clinical evidence and clinical data obtained with different technical approaches

Near Infared Circularly Polarized Luminescence From Water Stable Organic Nanoparticles Containing a Chiral Yb(III) Complex

We report the first example of very efficient NIR Circularly Polarized Luminescence (CPL) (around 970 nm) in water, obtained thanks to the combined use of a chiral Yb complex and of poly lactic-co-glycolic acid (PLGA) nanoparticles. [YbL(tta)2]CH3COO (L=N, N’-bis(2-pyridylmethylidene)-1,2-(R,R+S,S) cyclohexanediamine and tta=2-thenoyltrifluoroacetonate) shows good CPL in organic solvents, because the tta ligands efficiently sensitize Yb NIR luminescence and the readily prepared chiral ligand L endows the complex with the necessary dissymmetry. PLGA nanoparticles incorporate the complex and protect the metal ion from the intrusion of solvent molecules, while ensuring biocompatibility, water solubility and stability to the complex. Hydrophilic NIR-CPL optical probes can find applications in the field of NIR-CPL bio-assays

Circularly polarized activity from two photon excitable europium and samarium chiral bioprobes

In this contribution, two couples of cationic enantiomeric complexes [(R,R)-[LnL]Cl and (S,S)-[LnL]Cl, with Ln = Sm and Eu and L = N,N &amp; PRIME;-bis(2-pyridylmethyl)-1,2-(R,R or S,S)-cyclohexanediamine functionalized at sp(3) N with the picolinate antennae2] have been synthesized and spectroscopically characterized in polar protic solvents, such as water and methanol. The good sensitization of Sm(iii) and Eu(iii) luminescence by the picolinate antenna is documented, upon both a one photon absorption process (at about 330 nm) and a two photon absorption process (at 720 nm). The complexes exhibit good CPL activity, in particular for the magnetic dipole (MD) allowed transitions, which are the (4)G(5/2) &amp; RARR; H-6(5/2) (564 nm) of Sm(iii) and the D-5(0) &amp; RARR; F-7(1) (593 nm) of Eu(iii). Both complexes are highly stable in aqueous solution (log K = 20.13 for the EuL species chosen as the representative) and only one main species is present at physiological pH (7.4). Among the three possible isomeric complexes, DFT calculations on the Y(iii) counterpart reveal the highest stability of the C-1-symmetric cis-O, O-N, N isomer, in agreement with the presence of only one Eu(iii) emitting species in solution. Furthermore, one solvent molecule is bound to the metal ions, giving rise to 9-fold coordinated complexes. Preliminary biphotonic imaging experiments on the (S,S)-[EuL]Cl complex reveal that it can be easily internalized in two different cell lines (namely 293T cancer cells and THP-1 macrophages) with perinuclear diffuse localisation in the cytosol. Both Sm(iii) and Eu(iii) complexes can be considered promising candidates as NIR-to-RED in cellulo chiroptical bioprobes and a possible extension to the in vivo experiment will be further investigated