Luminescence of Eu3+ and Tb3+ Complexes of Two Macrobicyclic Ligands Derived from a Tetralactam Ring and a Chromophoric Antenna

Two macrobicyclic ligands derived from an 18‐membered tetralactam ring and 2,2′‐bipyridine or 2,6‐bis(pyrazol‐1‐yl)pyridine moieties, 1 and 2 , respectively, form stable complexes with Gd^III, Eu^III, and Tb^III ions in aqueous solution. The ligand‐based luminescence is retained in the Gd^III cryptates, whereas this radiative deactivation is quenched in the Eu^III and Tb^III cryptates by ligand‐to‐metal energy transfer, resulting in the usual metal‐centered emission spectra. Singlet‐ and triplet‐state energies, emission‐decay lifetimes, and luminescence yields were measured. [Tb⊂ 1 ]³⁺ cryptate shows a long luminescence lifetime (τ=1.12 ms) and a very high metal luminescence quantum yield (Φ=0.25) in comparison with those reported in the literature for Tb³⁺ complexes sensitized by a bipyridine chromophore. By comparison to [Ln⊂ 1 ]³⁺, [Ln⊂ 2 ]³⁺ presents markedly lower luminescence properties, due to worse interaction between the 2,6‐bis(pyrazol‐1‐yl)pyridine unit and the metal ion. Moreover, the luminescent metal and the triplet ligand energy levels of [Eu⊂ 2 ]³⁺ do not match. The effects of H₂O molecules coordinated to the metal centre and of thermally activated decay processes on nonradiative deactivation to the ground‐state are also reported.     

Comprehensive Evaluation of the Physicochemical Properties of LnIII Complexes of Aminoethyl‐DO3A as pH‐Responsive T1‐MRI Contrast Agents

N‐Substituted aminoethyl groups were attached to 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid (DO3A) with the aim to design pH‐responsive Ln^III complexes based on the pH‐dependent on/off ligation of the amine nitrogen to the metal ion. The following ligands were synthesized: AE ‐ DO3A (aminoethyl‐DO3A), MAE ‐ DO3A (N‐methylaminoethyl‐DO3A), DMAE ‐ DO3A (N,N‐dimethylaminoethyl‐DO3A) and MEM ‐ AE ‐ DO3A (N‐methoxyethyl‐N‐methylaminoethyl‐DO3A). The physicochemical properties of the Ln^III complexes were investigated for the evaluation of their potential applicability as magnetic resonance imaging (MRI) contrast agents. In particular, a ¹H and ¹⁷O NMR relaxometric study was carried out for these Gd^III complexes at two different pH values: at basic pH (pendant amino group coordinated to the metal centre) and at acidic pH (protonated amine, not interacting with the metal ion). Eu^III complexes allow one to estimate the number of inner‐sphere water molecules through luminescence lifetime measurements and obtain some structural information through variable‐temperature (VT) high‐resolution ¹H NMR studies. Equilibria between differently hydrated species were found for most of the complexes at both acidic and basic pH. The thermodynamic stability of Ca^II, Zn^II, Cu^II and Ln^III complexes and kinetics of formation and dissociation reactions of Ln^III complexes of AE ‐ DO3A and DMAE ‐ DO3A were investigated showing stabilities comparable to currently approved Gd^III‐based CAs. In detail, higher total basicity (Σlog K_i^H) and higher stability constants of Ln^III complexes were found for AE ‐ DO3A with respect to DMAE ‐ DO3A (i.e., log K_{Gd‐ AE‐DO3A} =22.40 and log K_{Gd‐ DMAE‐DO3A} =20.56). The transmetallation reactions of Gd^III complexes are very slow (Gd‐ AE ‐ DO3A : t_1/2=2.7×10⁴ h; Gd‐ DMAE ‐ DO3A : 1.1×10⁵ h at pH 7.4 and 298 K) and occur through proton‐assisted dissociation.     

Focal‐point anchoring: Large proton relaxivity observed for gadolinium‐cored dendrimer complexes in water

Water‐soluble Gd³⁺‐cored poly(ether amide) dendrimer complexes, bearing a diethylenetriaminepentaacetic acid Gd³⁺ complex (GdDTPA) core, were synthesized. The longitudinal proton relaxivity (R₁), governed mainly by the rotation correlation time of the paramagnetic Gd³⁺ center, was measured in water (37 °C, 20 MHz). An anchor effect at the focal point of the hydrophilic dendrimer was experimentally evaluated for the first time, through a comparison of the R₁ values with the ones reported for various Gd³⁺ complexes, including linear copolymers of GdDTPA linked by various lengths of aliphatic chains via amide bonds. Unusually large R₁ values for the first‐ and second‐generation Gd³⁺‐cored dendrimer complexes (6.1 and 9.3 mM^?1 s^?1, respectively), even with relatively low molecular weights (1355 and 3877, respectively), suggested a remarkable increase in the local rigidity around the GdDTPA core. The internal rigidity of the dendrimer was supposed to take advantage of the increased nominal molecular weight in water via multihydration to the dendron to increase the rotation correlation time, and this resulted in the observed R₁ gain. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2680–2689, 2004     

Solvent-dependent chromogenic sensing for Cu and fluorogenic sensing for Zn and Al: a multifunctional chemosensor with dual-mode

A new multifunctional chemosensor 1 was synthesized and characterized by spectroscopic tools along with a single crystal X-ray crystallography. It can exhibit selective recognition responses toward Cu²⁺, Zn²⁺ and Al³⁺ in different solvent systems with bimodal methods (colorimetric and fluorescence). This sensor 1 detected Cu²⁺ ions through a distinct color change from colorless to yellow in aqueous solution. Interestingly, the receptor 1 was found to be reversible by EDTA. The detection limit (11 μM) of 1 for Cu²⁺ is much lower than WHO guideline (30 μM) in drinking water. In addition, the sensor 1 showed significant fluorescence enhancements in the presence of Zn²⁺ ion and Al³⁺ ion in two different organic solvents (DMF and MeCN), respectively. The binding modes of the three complexes were determined to be a 1:1 complexation stoichiometry through Job plot, ESI-mass spectrometry analysis, and ¹H NMR titration.     

Supramolecular arrangement and photophysical properties of a dinuclear cyanophenylboronic acid ester

Boronic esters are useful building blocks for crystal engineering and the generation of supramolecular architectures, including macrocycles, cages and polymers (one‐, two‐ and three‐dimensional), with potential utility in diverse fields such as separation, storage and luminescent materials. The novel dinuclear cyanophenylboronic ester described herein, namely 4,4′‐(2,4,8,10‐tetraoxa‐3,9‐diboraspiro[5.5]undecane‐3,9‐diyl)dibenzonitrile, C₁₉H₁₆B₂N₂O₄, was prepared by condensation of 4‐cyanophenylboronic acid and pentaerythritol and fully characterized by elemental analysis, IR and NMR (¹H and ¹¹B) spectroscopy, single‐crystal X‐ray diffraction analysis and TG‐DSC (thermogravimetry–differential scanning calorimetry) studies. In addition, the photophysical properties were examined in solution and in the solid state by UV–Vis and fluorescence spectroscopies. Density functional theory (DFT) calculations with ethanol as solvent reproduced reasonably well the HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) of the title compound. Hirshfeld surface and fingerprint plot analyses are presented to illustrate the supramolecular connectivity in the solid state.     

Reactive EC(p‐p)π‐systems 53 [1]: Reactivity studies on perfluoro‐2‐arsapropene: [2+2]‐cycloaddition reactions and quantum chemical calculations

The extremely labile perfluoro‐2‐arsapropene F₃CAsCF₂ ( 1 ) has been generated by an improved pyrolysis process of Me₃SnAs(CF₃)₂ and found to be stabilized by the presence of hexamethyldisiloxane and tert‐butylphosphaethyne, thus allowing (i) reactivity studies with alkyne derivatives like tBuCP, (iPr)₂NCP, MeCCN(iPr)₂, HCCOEt and (ii) a full NMR investigation of 1 (¹⁹F, ¹³C). Due to the instability of 1 and some of the products, the [2+2]‐cycloaddition reactions gave the expected arsaphospha‐ and arsa‐cyclobutene derivatives, respectively, in moderate to good yields, but in some cases contaminated with side and/or decomposition products. Unequivocal characterization of the novel compounds was accomplished by spectroscopic in‐ vestigations (¹H, ¹³C, ¹⁹F, ³¹P NMR, IR, MS) supported by comparison with the data of the more stable phosphorus analogues. An interesting isomerization was observed for the 2‐dialkylamino‐4,4‐difluoro‐ 1‐trifluoromethyl‐1‐arsa‐3‐phospha‐2‐cyclobutenes yielding the more stable 3‐dialkylamino‐2,4‐difluoro‐ 1‐trifluoromethyl‐1‐arsa‐2‐phospha‐3‐cyclobutenes. Quantum chemical calculations [B3LYP/6‐311+ G(d,p)] of HAsCH₂, F₃CAsCF₂, and F₃CPCF₂ were carried out to compare the length of the AsC double bond with the literature data and to elucidate substituent effects on its electronic structure. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:406–419, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20118     

Experimental and quantum chemical calculational studies on N‐[4‐(3‐Methyl‐3‐phenyl‐cyclobutyl)‐thiazol‐2‐yl]‐N′‐pyridin‐3ylmethylene‐hydrazine

The title molecule, N‐[4‐(3‐Methyl‐3‐phenyl‐cyclobutyl)‐thiazol‐2‐yl]‐N′‐pyridin‐3ylmethylene‐ hydrazine (C₂₀ H₂₀ N₄ S₁), was characterized by ¹H‐NMR, ¹³C‐NMR, IR, UV‐visible, and X‐ray determination. In addition to the molecular geometry from X‐ray experiment, the molecular geometry, vibrational frequencies and gauge including atomic orbital ¹H‐ and ¹³C‐NMR chemical shift values of the title compound in the ground state have been calculated using the Hartree‐Fock and density functional method (B3LYP) with 6‐31G(d, p) basis set. The calculated results show that optimized geometries can well reproduce the crystal structural parameters. By using time‐dependent density functional theory method, electronic absorption spectrum of the title compound has been predicted. © 2011 Wiley Periodicals, Inc.     

Recyclizations of 2‐aminobenzylimines and thioaroylhydrazones of N‐substituted N‐hydroxy‐3‐oxobutanamides

A universal scheme is proposed for the molecular design of heterocyclic recyclizations by replacing the exocyclic hydroxyl groups in exo‐trig‐ ring‐chain tautomeric molecules with substituted amines or hydrazines. The practical applicability of this approach is demonstrated by the condensations of 5‐hydroxy‐5‐methyl‐3‐isoxazolidinones with thioaroyl‐hydrazines and 2‐aminomethylaniline. The condensation products were studied by modern ¹H, ¹³C and ¹⁵N NMR spectroscopic methods using three solvents: CDC1₃, DMSO[D₆] and CD₃CN. The solvent was found to have a strong effect to the relative amounts of the tautomers.     

NMR Characterization of Lanthanide(3+) Complexes of Tetraazatetrakisphosphinato and Tetraazatetra­kisphosphonato Ligands

The three‐dimensional structures in aqueous solution of the entire series of the Ln³⁺ complexes [Ln(DOTP*‐Et)]^? (formed from the free ligand P,P′,P″,P′′′‐[1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(methylene)]tetrakis[P‐ethylphosphinic acid] (H₄DOTP*‐Et) were studied by NMR techniques to rationalize the parameters governing the relaxivity of the Gd³⁺ complex and evaluate its potential as MRI contrast agent. From the ¹H‐ and ³¹P‐NMR lanthanide‐induced‐shift (LIS) values, especially of the [Yb(DOTP*‐Et)]^? complex, it was concluded that the [Ln(DOTP*‐Et)]^? complexes adopt in solution twisted square antiprismatic coordination geometries which change gradually their coordination‐cage structure along the lanthanide series. These complexes have no inner‐sphere‐H₂O coordination, and preferentially have the (R,R,R,R) configuration of the P‐atoms in the pendant arms. Self‐association was observed in aqueous solution for the tetraazatetrakisphosphonic acid ester complexes [Ln(DOTP*‐OEt)]^? (=[Ln(DOTP‐Et)]^?) and [Ln(DOTP*‐OBu)]^? (=[Ln(DOTP‐Bu)]^?) at and above 5 mM concentration, through analysis of ³¹P‐NMR, EPR, vapor‐pressure‐osmometry, and luminescence‐spectroscopic data. The presence of the cationic detergent cetylpyridinium chloride (CPC; but not of neutral surfactants) shifts the isomer equilibrium of [Eu(DOTP*‐OBu)]^? to the (S,S,S,S) form which selectively binds to the cationic micelle surface.     

Synthesis and Structural Characterization of Cadmium(II) and Mercury(II) Complexes Derived from 3‐Aminoquinoline

Two novel metal complexes derived from interactions of Cd²⁺ and Hg²⁺ ions with 3‐aminoquinoline in the molar ratio 1 : 2 are reported. The synthesized and isolated metal complexes were characterized by UV/VIS, FT‐IR, ¹H‐ and ¹³C‐NMR, and ESI‐MS spectroscopic studies, and elemental analyses. FT‐IR and NMR studies confirmed that the NH₂ group remains uncoordinated in both synthesized complexes. The molecular structure of the Cd^II complex was additionally determined by X‐ray single‐crystal analysis. The Cd complex crystallizes in the triclinic centrosymmetric P$\bar 1$ space group. Moreover, the Cd^II complex exists as neutral discrete molecule and was found to show tetrahedral geometry.     

Synthesis and trivalent lanthanide ion complexation studies of new macrocyclic receptors based lactam ionophores

This study is the first report on the design, synthesis and photophysical properties of three new macrocyclic receptors based receptors containing two amide bridges. Their binding properties towards trivalent lanthanide ions such as La³⁺, Gd³⁺, Tb³⁺, Dy³⁺, Er³⁺ and Yb³⁺ were investigated by using spectroscopic techniques. With respect to emission intensity changes upon trivalent lanthanide ion complexation, macrocyclic receptors based lactam ionophores showed higher selectivity towards Yb³⁺ and/or Er³⁺ ion over other ions. Presence of proximal two amide groups in macrocyclic lactam receptors having different cavity size were observed to play an important role in exhibiting its lanthanide ion binding.     

A New Irregular Trihydroxy Sesquiterpene from Teucrium mascatense

A new trihydroxy sesquiterpene, rel‐(1R,4aR,5S,6S,7S,8aR)‐decahydro‐6,8a‐dimethyl‐5‐(propan‐2‐yl)naphthalene‐1,6,7‐triol ( 1 ), has been isolated as a result of the phytochemical investigation on the CH₂Cl₂ extract of Teucrium mascatense. The structure elucidation of the new constituent was carried out by the combined use of 1D‐ (¹H‐ and ¹³C‐NMR) and 2D‐NMR (HMBC and HSQC) spectroscopic analysis, along with mass spectrometric techniques. In addition to the new constituent 1 , the known metabolite 2 , previously isolated from Crataegus pinnatifida, was also identified.     

The turn-off fluorescent sensors based on thioether-linked bisbenzamide for Fe3+ and Hg2+

Some dibenzamide derivatives with a thioether linker were designed, synthesized and characterized. The specific responses to Hg²⁺ and Fe³⁺ were investigated by fluorescence. According to fluorescence titration, the Job plot, ¹H NMR, and ESI-mass analysis, the derivative with mono-hydroxyl substituent (1b) on the aromatic ring has high selectivity for Fe³⁺ ion with the formation of 1:1 1b-Fe³⁺ complexes. The specificity of 1c for Hg²⁺ could be switched by swapping the substituent from hydroxyl to amino, and a 1:2 (1c-Hg²⁺) complex was formed. Along with the obtained results, density functional theory (DFT) and natural bond orbital (NBO) analyses, Time-dependent (TD) DFT and natural transition orbital (NTO) analyses were employed to explore the geometric structures, properties and possible mechanisms.     

New Antifungal `Quinone Methide' Diterpenes from Bobgunnia madagascariensis and Study of Their Interconversion by LC/NMR

Two new `quinone methide' diterpenes with a cassane skeleton were isolated from the root bark of Bobgunnia madagascariensis (Desv. ) J. H. Kirkbr. & Wiersema (Leguminosae). The two compounds occurred as a diastereoisomer mixture 1 / 2 . Their structure was established as (4R,6aS,10aS)‐ and (4S,6aS,10aS)‐ 1,4,6a,7,8,9,10,10a‐octahydro‐4,11‐dihydroxy‐7,7,10a‐trimethyl‐2H‐phenanthro[1,2‐c]pyran‐6,12‐dione by spectroscopic methods and by comparison with the data obtained for another `quinone methide' diterpene isolated previously from the same plant and identified by single‐crystal X‐ray analysis. ¹H‐ and ¹³C‐NMR signals were assigned by extensive in‐mixture 2D correlation experiments, and ¹H‐NMR spectra of the separated diastereoisomers 1 and 2 were recorded by on‐flow LC/NMR. The interconversion of 1 and 2 was followed by repeated stop‐flow LC/NMR experiments over a two‐hour period. Compounds 1 and 2 showed moderate antifungal properties towards human pathogenic fungi, in particular the yeast Candida albicans.     

Manganese(III) Acetate Catalyzed Oxidative Radical Additions of α‐Dicarbonyl Compounds to 1‐ and 2‐Phenylcyclohepta‐1,3,5‐triene

Manganese(III) acetate catalyzed oxidative radical‐addition reactions of α‐dicarbonyl compounds such as methyl acetoacetate ( 6 ), acetylacetone ( 7 ), and dimedone ( 8 ) to the mixture of 1‐ and 2‐phenylcyclohepta‐1,3,5‐triene ( 4 and 5 ) were investigated (Scheme 1). The 1‐phenylcyclohepta‐1,3,5‐triene ( 4 ) formed mainly [2+3] and [4+3] dihydrofuran addition products derived from cycloheptatriene and [2+3] dihydrofuran addition products derived from the norcaradiene structure. The 2‐phenylcyclohepta‐1,3,5‐triene ( 5 ) formed mainly [6+3] dihydrofuran addition products derived from cycloheptatriene and [4+3] dihydrofuran addition products derived from the norcaradiene structure. The structures of isolated products were established by their spectroscopic data (IR, ¹H‐ and ¹³C‐NMR, MS, and elemental analysis) and comparison with literature data. The formation mechanism of the products is discussed.     

Diastereochemical differentiation of bicyclic diols using metal complexation and collision‐induced dissociation mass spectrometry

Metal complex formation was investigated for di‐exo‐, di‐endo‐ and trans‐2,3‐ and 2,5‐disubstituted trinorbornanediols, and di‐exo‐ and di‐endo‐ 2,3‐disubstituted camphanediols using different divalent transition metals (Co²⁺, Ni²⁺, Cu²⁺) and electrospray ionization quadrupole ion trap mass spectrometry. Many metal‐coordinated complex ions were formed for cobalt and nickel: [2M+Met]²⁺, [3M+Met]²⁺, [M–H+Met]⁺, [2M–H+Met]⁺, [M+MetX]⁺, [2M+MetX]⁺ and [3M–H+Co]⁺, where M is the diol, Met is the metal used and X is the counter ion (acetate, chloride, nitrate). Copper showed the weakest formation of metal complexes with di‐exo‐2,3‐disubstituted trinorbornanediol yielding only the minor singly charged ions [M–H+Cu]⁺, [2M–H+Cu]⁺ and [2M+CuX]⁺. No clear differences were noted for cobalt complex formation, especially for cis‐2,3‐disubstituted isomers. However, 2,5‐disubstituted trinorbornanediols showed moderate diastereomeric differentiation because of the unidentate nature of the sterically more hindered exo‐isomer. trans‐Isomers gave rise to abundant [3M–H+Co]⁺ ion products, which may be considered a characteristic ion for bicyclo[221]heptane trans‐2,3‐ and trans‐2,5‐diols. To differentiate cis‐2,3‐isomers, the collision‐induced dissociation (CID) products for [3M+Co]²⁺, [M+CoOAc]⁺, [2M–H+Co]⁺ and [2M+CoOAc]⁺ cobalt complexes were investigated. The results of the CID of the monomeric and dimeric metal adduct complexes [M+CoOAc]⁺ and [2M–H+Co]⁺ were stereochemically controlled and could be used for stereochemical differentiation of the compounds investigated. In addition, the structures and relative energies of some complex ions were studied using hybrid density functional theory calculations. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis,Spectroscopic Characterization,DFT Calculations,and Dynamic Behavior of Mononuclear Macrocyclic Diorganotin(IV) Bis‐Dithiocarbamate Complexes

Nine mononuclear diorganotin(IV) dithiocarbamate complexes 1 – 9 with 19‐, 20‐ and 21‐membered macrocyclic structures were synthesized from dimethyl, di‐n‐butyl, and diphenyltin(IV) dichloride and three bis‐dithiocarbamate ligands derived from secondary bis‐amines having aromatic spacer groups. All compounds were characterized by elemental analysis, mass spectrometry, and spectroscopic methods (IR and ¹H, ¹³C, and ¹¹⁹Sn NMR). Additionally, quantum chemical DFT calculations were performed for the dimethyltin(IV) derivatives in order to model the molecular structures. For one compound series the NMR spectra showed a concentration‐dependent behavior in solution, which was analyzed in detail and permitted to postulate the existence of an equilibrium with the corresponding [2+2] macrocycles.     

Tri- and tetraurea piperazine cyclophanes: synthesis and complexation studies of preorganized and folded receptor molecules

A series of symmetrical tri‐ and tetrameric N‐ethyl‐ and N‐phenylurea‐functionalized cyclophanes have been prepared in nearly quantitative yields (86–99 %) from the corresponding tri‐ and tetraamino‐functionalized piperazine cyclophanes and ethyl or phenyl isocyanates. Their conformational and complexation properties have been studied by single‐crystal X‐ray diffraction, variable‐temperature NMR spectroscopy, and ESI‐MS analysis. The rigid 27‐membered trimeric cyclophane skeleton assisted by a seam of intramolecular hydrogen bonds results in a preorganized ditopic recognition site with an all‐syn conformation of the urea moieties that, complemented by a lipophilic cavity of the cyclophane, binds molecular and ionic guests as well as ion pairs. The all‐syn conformation persists in acidic conditions and the triprotonated triurea cyclophane binds an unprecedented anion pair, H₂PO₄^????HPO₄^2?, in the solid state. The tetra‐N‐ethylurea cyclophane is less rigid and demonstrates an induced‐fit recognition of diisopropyl ether in the solid state. The guest was encapsulated within the lipophilic interior of a quasicapsule, formed by intramolecular hydrogen‐bond‐driven folding of the 36‐membered cyclophane skeleton. In the gas phase, the essential role of the urea moieties in the binding was demonstrated by the formation of monomeric 1:1 complexes with K⁺, TMA⁺, and TMP⁺ as well as the ion‐pair complexes [KI+K]⁺, [TMABr+TMA]⁺ and [TMPBr+TMP]⁺. In the positive‐mode ESI‐MS analysis, ion‐pair binding was found to be more pronounced with the larger tetraurea cyclophanes. In the negative mode, owing to the large size of the binding site, a general binding preference towards larger anions, such as the iodide, over smaller anions, such as the fluoride, was observed.     

Complexation and Catenation in Aqueous Media Using a Self‐Assembled PdII Metallacyclic Receptor

A M₂L₂ rectangular‐shaped metallacycle, obtained by metal‐directed self‐assembly of a 2‐(pyridin‐4‐ylmethyl)‐2,7‐diazapyrenium salt and [(en)Pd (NO₃)₂] (en=ethylenediamine), has been investigated as a molecular receptor for a wide range of aromatic substrates in water. Complexation and catenation of the receptor with selected mono‐ and polycyclic aromatic substrates produced 1:1 inclusion complexes and [2]catenanes in a highly efficient fashion, as determined by NMR and UV/Vis spectroscopic techniques, as well as single‐crystal X‐ray crystallography. Furthermore, the thermodynamic and kinetic features of the complexation processes have been analyzed for selected model guests.     

Activatable 19F MRI Nanoparticle Probes for the Detection of Reducing Environments

¹⁹F magnetic resonance imaging (MRI) probes that can detect biological phenomena such as cell dynamics, ion concentrations, and enzymatic activity have attracted significant attention. Although perfluorocarbon (PFC) encapsulated nanoparticles are of interest in molecular imaging owing to their high sensitivity, activatable PFC nanoparticles have not been developed. In this study, we showed for the first time that the paramagnetic relaxation enhancement (PRE) effect can efficiently decrease the ¹⁹F NMR/MRI signals of PFCs in silica nanoparticles. On the basis of the PRE effect, we developed a reduction‐responsive PFC‐encapsulated nanoparticle probe, FLAME‐SS‐Gd³⁺ (FSG). This is the first example of an activatable PFC‐encapsulated nanoparticle that can be used for in vivo imaging. Calculations revealed that the ratio of fluorine atoms to Gd³⁺ complexes per nanoparticle was more than approximately 5.0×10², resulting in the high signal augmentation.