A first series of polyanils were synthesized by a simple condensation between either isomers of phenylenediamine derivatives or 1,3,5-benzenetriamine and 4-(diethylamino)salicylaldehyde, while a ...second series resulted from the condensation between 4,6-dihydroxyisophthalaldehyde or 2,5-dihydroxyterephthalaldehyde and differently substituted anilines. All these polyanils showed good chelating abilities toward trivalent boron fragments such as BF2 or BPh2 to yield the corresponding boranils. The optical properties of these novel fluorophores have been studied both in solution and in the solid-state and show emission wavelengths covering the entire visible spectrum and near-infrared (NIR), depending on molecular structure, substitution, and environment. While faintly fluorescent in solution in their molecular state, some polyanils show typical aggregation-induced emission (AIE) behavior upon addition of increasing amounts of water in THF solution, leading to a sizable enhancement of fluorescence intensity.
Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery ...procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer's disease, or cardiovascular diseases. Among all the available PET-active radionuclides,
F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t
= 109.77 min; 97% β
emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies.
2‐(2’‐Hydroxyphenyl)benzazole (HBX) fluorophores are well‐known excited‐state intramolecular proton transfer (ESIPT) emitters largely studied for their synthetic versatility, photostability, strong ...solid‐state fluorescence and ability to engineer dual emission, thus paving the way to applications as white emitters, ratiometric sensors, and cryptographic dyes. However, they are heavily quenched in solution, due to efficient non‐radiative pathways taking place as a consequence of the proton transfer in the excited‐state. In this contribution, the nature of the heteroring constitutive of these rigidified HBX dyes was modified and we demonstrate that this simple structural modification triggers major optical changes in terms of emission color, dual emission engineering, and importantly, fluorescent quantum yield. Investigation of the photophysical properties in solution and in the solid state of a series of ethynyl‐TIPS extended HBX fluorophores, along with ab initio calculations demonstrate the very promising abilities of these dyes to act as bright dual‐state emitters, in both solution (even in protic environments) and solid state.
A series of HBX derivatives (HBX=(2‐(2’‐hydroxyphenyl)benzazole)), mono‐ or bis‐functionalized with ethynyl‐TIPS substituents at various positions, were synthesized and characterized structurally and spectroscopically. Variation of the nature of the heteroring revealed a strong influence of the heteroatom, in terms of emission wavelength, stabilization of the first excited‐state and most importantly quantum yields values.
Dual solution/solid‐state emissive fluorophores based on a 2‐(2′‐Hydroxyphenyl)benzoxazole (HBO) core bearing one or two ethynyl‐tolyl moieties at different positions were synthesized via an expedite ...two‐step synthetic procedure. HBO derivatives are known to display intense Excited‐State Intramolecular Proton Transfer (ESIPT) emission in the solid‐state but are mildly emissive in solution due to the detrimental flexibility of the excited‐state opening efficient non‐radiative pathways. The sole introduction of a rigid ethynyl moiety led to a sizeable enhancement of the fluorescence quantum yield in solution, up to a 15‐fold increase in toluene as compared to unsubstituted HBO dyes while keeping the high solid‐state fluorescence efficiency. The position of the substitution on the π‐conjugated core led to subtle fine‐tuning of maximum emission wavelengths and quantum yields. Moreover, we show that the ethynyl tolyl substituent at the para position of the phenol ring is a suitable moiety for an efficient stabilization of the corresponding emissive anionic HBO derivatives in dissociative solvents like DMF THF or EtOH. These observations were confirmed in CH3CN by a basic titration. For all dyes, the nature of the excited‐state involved in the fluorescence emission was rationalized using ab initio calculations.
A series of ESIPT emitters based on ethynyl‐extended HBO scaffolds has been synthesized. Their optical properties reveal increased quantum yields values in solution as compared to unsubstituted analogues while keeping strong fluorescence intensities in the solid‐state. These scaffolds also allow the stabilization of an anionic species in selected cases, as evidenced by basic titrations. The nature of the excited‐states was also rationalized using ab initio calculations.
Purpose
Overexpression and activation of matrix metalloproteinase-13 (MMP-13) within atheroma increases susceptibility to plaque rupture, a major cause of severe cardiovascular complications. In ...comparison to pan-MMP targeting
18
FBR-351, we evaluated the potential for
18
FFMBP, a selective PET radiotracer for MMP-13, to detect extracellular matrix (ECM) remodeling in vascular plaques possessing markers of inflammation.
Procedures
18
FFMBP and
18
FBR-351 were initially assessed
in vitro
by incubation with
en face
aortae from 8 month-old atherogenic
ApoE
−/−
mice.
Ex vivo
biodistributions, plasma metabolite analyses, and
ex vivo
autoradiography were analogously performed 30 min after intravenous radiotracer administration in age-matched C57Bl/6 and
ApoE
−/−
mice under baseline or homologous blocking conditions.
En face
aortae were subsequently stained with Oil Red O (ORO), sectioned, and subject to immunofluorescence staining for Mac-2 and MMP-13.
Results
High-resolution autoradiographic image analysis demonstrated target specificity and regional concordance to lipid-rich lesions. Biodistribution studies revealed hepatobiliary excretion, low accumulation of radioactivity in non-excretory organs, and few differences between strains and conditions in non-target organs. Plasma metabolite analyses uncovered that
18
FFMBP exhibited excellent
in vivo
stability (≥74% intact) while
18
FBR-351 was extensively metabolized (≤37% intact).
Ex vivo
autoradiography and histology of
en face
aortae revealed that
18
FFMBP, relative to
18
FBR-351, exhibited 2.9-fold greater lesion uptake, substantial specific binding (68%), and improved sensitivity to atherosclerotic tissue (2.9-fold
vs
2.1-fold). Immunofluorescent staining of aortic
en face
cross sections demonstrated elevated Mac-2 and MMP-13-positive areas within atherosclerotic lesions identified by
18
FFMBP
ex vivo
autoradiography.
Conclusions
While both radiotracers successfully identified atherosclerotic plaques,
18
FFMBP showed superior specificity and sensitivity for lesions possessing features of destructive plaque remodeling. The detection of ECM remodeling by selective targeting of MMP-13 may enable characterization of high-risk atherosclerosis featuring elevated collagenase activity.
This article describes the synthetic efforts towards the solubilization of organic fluorescent emitters based on a 2-(2'-hydroxybenzofuranyl)benzazole (HBBX) scaffold in aqueous media under ...physiological conditions (PBS, pH 7.4). These dyes are well-known to display the excited-state intramolecular proton transfer (ESIPT) process which leads to a Stokes-shifted fluorescence with enhanced photostability and strong environment dependent features. Organic dyes are hydrophobic by nature and their vectorization into aqueous media usually necessitates amphiphilic polymers. In this study, we show that the incorporation of one or two sulfobetaine fragments, a highly biocompatible zwitterionic unit leads to the vectorization in buffer solution at pH 7.4 while keeping a reasonable ESIPT fluorescence emission. The photophysical properties of all dyes were studied in multiple solvents and showed that, depending on structure and environment, different excited-state species are observed: normal or tautomeric species, as well as a competitive anionic fluorescent derivative. This study shows that it is not only possible to solubilize fluorescent ESIPT dyes in water using sulfobetaine(s) but also that the optical properties can be finely tuned depending on small structural inputs.
Carbazole/cyanobenzene photocatalysts promote the direct isotopic carboxylate exchange of C(sp3) acids with labeled CO2. Substrates that are not compatible with transition-metal-catalyzed ...degradation–reconstruction approaches or prone to thermally induced reversible decarboxylation undergo isotopic incorporation at room temperature in short reaction times. The radiolabeling of drug molecules and precursors with 11CCO2 is demonstrated.
Fast and straightforward incorporation of radionuclides into pharmaceutically relevant molecules is one of the main barriers to preclinical and clinical tracer research. Late-stage direct ...incorporation of cyclotron-produced
CCO
to afford carbon-11-labeled radiopharmaceuticals has the potential to provide ready-to-inject positron emission tomography agents in less than an hour. The present work describes photocatalyzed carboxylation of alkylbenzene derivatives to afford
C-phenylacetic acids. Reaction conditions and scope are investigated followed by application of this methodology to the preparative radiosynthesis of
Cfenoprofen, a nonsteroidal anti-inflammatory drug.
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