Six-coordinate Iron(II) and Cobalt(II) paraSHIFT Agents for Measuring Temperature by Magnetic Resonance Spectroscopy

<u>Para</u>magnetic Fe­(II) and Co­(II) complexes are utilized as the first transition metal examples of ¹H NMR <u>shift</u> agents (paraSHIFT) for thermometry applications using <u>M</u>agnetic <u>R</u>esonance <u>S</u>pectroscopy (MRS). The coordinating ligands consist of TACN (1,4,7-triazacyclononane) and CYCLEN (1,4,7,10-tetraazacyclododecane) azamacrocycles appended with 6-methyl-2-picolyl groups, denoted as MPT and TMPC, respectively. ¹H NMR spectra of the MPT- and TMPC-based Fe­(II) and Co­(II) complexes demonstrate narrow and highly shifted resonances that are dispersed as broadly as 440 ppm. The six-coordinate complex cations, [M­(MPT)]²⁺ and [M­(TMPC)]²⁺, vary from distorted octahedral to distorted trigonal prismatic geometries, respectively, and also demonstrate that 6-methyl-2-picolyl pendents control the rigidity of these complexes. Analyses of the ¹H NMR chemical shifts, integrated intensities, line widths, the distances obtained from X-ray diffraction measurements, and longitudinal relaxation time (<i>T</i>₁) values allow for the partial assignment of proton resonances of the [M­(MPT)]²⁺ complexes. Nine and six equivalent methyl protons of [M­(MPT)]²⁺ and [M­(TMPC)]²⁺, respectively, produce 3-fold higher ¹H NMR intensities compared to other paramagnetically shifted proton resonances. Among all four complexes, the methyl proton resonances of [Fe­(TMPC)]²⁺ and [Co­(TMPC)]²⁺ at −49.3 ppm and −113.7 ppm (37 °C) demonstrate the greatest temperature dependent coefficients (CT) of 0.23 ppm/°C and 0.52 ppm/°C, respectively. The methyl groups of these two complexes both produce normalized values of |CT|/fwhm = 0.30 °C^–1, where fwhm is full width at half-maximum (Hz) of proton resonances. The <i>T</i>₁ values of the highly shifted methyl protons are in the range of 0.37–2.4 ms, allowing rapid acquisition of spectroscopic data. These complexes are kinetically inert over a wide range of pH values (5.6–8.6), as well as in the presence of serum albumin and biologically relevant cations and anions. The combination of large hyperfine shifts, large temperature sensitivity, increased signal-to-noise ratio, and short <i>T</i>₁ values suggests that these complexes, in particular the TMPC-based complexes, show promise as paraSHIFT agents for thermometry

Six-coordinate Iron(II) and Cobalt(II) paraSHIFT Agents for Measuring Temperature by Magnetic Resonance Spectroscopy

<u>Para</u>magnetic Fe­(II) and Co­(II) complexes are utilized as the first transition metal examples of ¹H NMR <u>shift</u> agents (paraSHIFT) for thermometry applications using <u>M</u>agnetic <u>R</u>esonance <u>S</u>pectroscopy (MRS). The coordinating ligands consist of TACN (1,4,7-triazacyclononane) and CYCLEN (1,4,7,10-tetraazacyclododecane) azamacrocycles appended with 6-methyl-2-picolyl groups, denoted as MPT and TMPC, respectively. ¹H NMR spectra of the MPT- and TMPC-based Fe­(II) and Co­(II) complexes demonstrate narrow and highly shifted resonances that are dispersed as broadly as 440 ppm. The six-coordinate complex cations, [M­(MPT)]²⁺ and [M­(TMPC)]²⁺, vary from distorted octahedral to distorted trigonal prismatic geometries, respectively, and also demonstrate that 6-methyl-2-picolyl pendents control the rigidity of these complexes. Analyses of the ¹H NMR chemical shifts, integrated intensities, line widths, the distances obtained from X-ray diffraction measurements, and longitudinal relaxation time (<i>T</i>₁) values allow for the partial assignment of proton resonances of the [M­(MPT)]²⁺ complexes. Nine and six equivalent methyl protons of [M­(MPT)]²⁺ and [M­(TMPC)]²⁺, respectively, produce 3-fold higher ¹H NMR intensities compared to other paramagnetically shifted proton resonances. Among all four complexes, the methyl proton resonances of [Fe­(TMPC)]²⁺ and [Co­(TMPC)]²⁺ at −49.3 ppm and −113.7 ppm (37 °C) demonstrate the greatest temperature dependent coefficients (CT) of 0.23 ppm/°C and 0.52 ppm/°C, respectively. The methyl groups of these two complexes both produce normalized values of |CT|/fwhm = 0.30 °C^–1, where fwhm is full width at half-maximum (Hz) of proton resonances. The <i>T</i>₁ values of the highly shifted methyl protons are in the range of 0.37–2.4 ms, allowing rapid acquisition of spectroscopic data. These complexes are kinetically inert over a wide range of pH values (5.6–8.6), as well as in the presence of serum albumin and biologically relevant cations and anions. The combination of large hyperfine shifts, large temperature sensitivity, increased signal-to-noise ratio, and short <i>T</i>₁ values suggests that these complexes, in particular the TMPC-based complexes, show promise as paraSHIFT agents for thermometry

Six-coordinate Iron(II) and Cobalt(II) paraSHIFT Agents for Measuring Temperature by Magnetic Resonance Spectroscopy

<u>Para</u>magnetic Fe­(II) and Co­(II) complexes are utilized as the first transition metal examples of ¹H NMR <u>shift</u> agents (paraSHIFT) for thermometry applications using <u>M</u>agnetic <u>R</u>esonance <u>S</u>pectroscopy (MRS). The coordinating ligands consist of TACN (1,4,7-triazacyclononane) and CYCLEN (1,4,7,10-tetraazacyclododecane) azamacrocycles appended with 6-methyl-2-picolyl groups, denoted as MPT and TMPC, respectively. ¹H NMR spectra of the MPT- and TMPC-based Fe­(II) and Co­(II) complexes demonstrate narrow and highly shifted resonances that are dispersed as broadly as 440 ppm. The six-coordinate complex cations, [M­(MPT)]²⁺ and [M­(TMPC)]²⁺, vary from distorted octahedral to distorted trigonal prismatic geometries, respectively, and also demonstrate that 6-methyl-2-picolyl pendents control the rigidity of these complexes. Analyses of the ¹H NMR chemical shifts, integrated intensities, line widths, the distances obtained from X-ray diffraction measurements, and longitudinal relaxation time (<i>T</i>₁) values allow for the partial assignment of proton resonances of the [M­(MPT)]²⁺ complexes. Nine and six equivalent methyl protons of [M­(MPT)]²⁺ and [M­(TMPC)]²⁺, respectively, produce 3-fold higher ¹H NMR intensities compared to other paramagnetically shifted proton resonances. Among all four complexes, the methyl proton resonances of [Fe­(TMPC)]²⁺ and [Co­(TMPC)]²⁺ at −49.3 ppm and −113.7 ppm (37 °C) demonstrate the greatest temperature dependent coefficients (CT) of 0.23 ppm/°C and 0.52 ppm/°C, respectively. The methyl groups of these two complexes both produce normalized values of |CT|/fwhm = 0.30 °C^–1, where fwhm is full width at half-maximum (Hz) of proton resonances. The <i>T</i>₁ values of the highly shifted methyl protons are in the range of 0.37–2.4 ms, allowing rapid acquisition of spectroscopic data. These complexes are kinetically inert over a wide range of pH values (5.6–8.6), as well as in the presence of serum albumin and biologically relevant cations and anions. The combination of large hyperfine shifts, large temperature sensitivity, increased signal-to-noise ratio, and short <i>T</i>₁ values suggests that these complexes, in particular the TMPC-based complexes, show promise as paraSHIFT agents for thermometry

Enhancing the Stability of Nicotine via Crystallization Using Enantiopure Tartaric Acid Salt Formers

Crystallization of nicotine, an oil prone to degradation at room temperature, has been demonstrated to be an effective means of creating nicotine-based materials with tunable thermal properties and improved resistance to photo-induced degradation. Herein, we show that both isomers of enantiomerically pure tartaric acid are highly effective salt formers when combined with nicotine. Both salts exhibit enhanced photostability, and with a melting point of 143.1 °C, the salt prepared using d-(−)-tartaric acid possesses one of the highest melting points for a crystalline nicotine solid reported to date

Enhancing the Stability of Nicotine via Crystallization Using Enantiopure Tartaric Acid Salt Formers

Crystallization of nicotine, an oil prone to degradation at room temperature, has been demonstrated to be an effective means of creating nicotine-based materials with tunable thermal properties and improved resistance to photo-induced degradation. Herein, we show that both isomers of enantiomerically pure tartaric acid are highly effective salt formers when combined with nicotine. Both salts exhibit enhanced photostability, and with a melting point of 143.1 °C, the salt prepared using d-(−)-tartaric acid possesses one of the highest melting points for a crystalline nicotine solid reported to date

Enhancing the Stability of Nicotine via Crystallization Using Enantiopure Tartaric Acid Salt Formers

Crystallization of nicotine, an oil prone to degradation at room temperature, has been demonstrated to be an effective means of creating nicotine-based materials with tunable thermal properties and improved resistance to photo-induced degradation. Herein, we show that both isomers of enantiomerically pure tartaric acid are highly effective salt formers when combined with nicotine. Both salts exhibit enhanced photostability, and with a melting point of 143.1 °C, the salt prepared using d-(−)-tartaric acid possesses one of the highest melting points for a crystalline nicotine solid reported to date

Phosphorescent organoplatinum(II) D₂A₂ metallacycles: synthesis, self-assembly, and photophysical properties

<p>A pair of organoplatinum(II) metallacycles, <b>M1</b> and <b>M2</b>, was self-assembled by combining one of two donor molecules, <i>cis</i>-[Pt(dhim)₂(C≡CC₅H₄N)₂] (<b>D1</b>; dhim = 1,3-dihexyl-2-H-imidazole-2-yelidene) and Pt(tbbpy)(C≡CC₅H₄N)₂ (<b>D2</b>; tbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine), with an acceptor precursor, Pt(tbbpy)(OTf)₂ (<b>A1</b>; OTf = CF₃SO₃⁻), respectively. Both donor molecules exhibit an idealized 90° angle between the coordination vectors of their ethynylpyridine moieties. When mixed with <b>A1</b>, coordination-driven self-assembly occurs at 50 °C (4 days in acetonitrile for <b>M1</b> and 18 h in CH₂Cl₂ for <b>M2</b>). Both metallacycles were characterized by ¹H NMR, FT-IR, and FT-ICR-MS techniques that support D₂A₂ self-assembly of molecular squares. The structure of building block <b>D1</b> was determined by X-ray diffraction, confirming the expected square coordination geometry and 90° orientation of the pyridyl coordination vectors. Photophysical studies of <b>M1</b> and <b>M2</b> reveal that the metallacycles display triplet emission bands at 466 and 469 nm, respectively, that originate from transitions localized on building blocks <b>D1</b> and <b>D2</b>. This phosphorescent behavior is assigned to ³ILCT and ³LLCT (<i>π</i>_C≡C* → <i>π</i>_C≡C; ILCT = intraligand charge transfer, LLCT = ligand-to-ligand charge transfer) transitions based on previous studies of phenyl analogs to <b>D1</b> and <b>D2</b> that indicate that the ethynyl moieties dominate in their contributions to the molecular orbitals involved in absorption and emission.</p

The Temperature Dependent Photoswitching of a Classic Diarylethene Monitored by <i>in Situ</i> X‑ray Diffraction

Organic photochromic molecules including diarylethenes are of particular interest for their numerous potential applications including high-density optical data storage and light-activated switches. In this report, we examined the temperature dependence of the light-drive photocyclization reaction in a classic diarylethene. The steady-state populations were monitored spectroscopically and by temperature dependent <i>in situ</i> photocrystallography, the latter being the first reported example of this technique. The observed decrease in the steady-state population with decreasing temperature suggests this classic diarylethene possesses an excited-state potential energy surface topology similar to previously reported “inverted” diarylethenes

Seven-Coordinate Co^II, Fe^II and Six-Coordinate Ni^II Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media

The solution chemistry and solid-state structures of the Co^II, Fe^II, and Ni^II complexes of 7,13-bis­(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (<b>L</b>) are reported as members of a new class of paramagnetic chemical exchange saturation transfer (paraCEST) MRI contrast agents that contain transition metal ions. Crystallographic data show that nitrogen and oxygen donor atoms of the macrocyclic ligand coordinate to the metal ions to generate complexes with distorted pentagonal bipyramidal geometry for [Co­(<b>L</b>)]­Cl₂·2H₂O or [Fe­(<b>L</b>)]­(CF₃SO₃)₂. The Ni^II complex [Ni­(<b>L</b>)]­(CF₃SO₃)₂·H₂O features a hexadentate ligand in a distorted octahedral geometry. The proton NMR spectra of all three complexes show highly dispersed and relatively sharp proton resonances. The complexes were further characterized by monitoring their dissociation under biologically relevant conditions including solutions containing phosphate and carbonate, ZnCl₂, or acidic conditions. Solutions of the paraCEST agents in 20 mM <i>N</i>-(2-hydroxyethyl)­piperazine-<i>N</i>′-ethanesulfonic acid (pH 7.4) and 100 mM NaCl showed highly shifted and intense CEST peaks at 59, 72, and 92 ppm away from bulk water for [Co­(<b>L</b>)]²⁺, [Ni­(<b>L</b>)]²⁺, and [Fe­(<b>L</b>)]²⁺, respectively at 37 °C on a 11.7 T NMR spectrometer. CEST spectra with corresponding rate constants for proton exchange are reported in 4% agarose gel (w/w), rabbit serum, egg white, or buffered solutions. CEST phantoms of 4 mM complex in buffer, 4% agarose gel (w/w), or rabbit serum on a 4.7 T MRI scanner at 37 °C, are compared. The most substantial change was observed for the reactive [Ni­(<b>L</b>)]²⁺, which showed reduced CEST contrast in rabbit serum and egg white. The complexes with the least highly shifted CEST peaks ([Co­(<b>L</b>)]²⁺ and [Ni­(<b>L</b>)]²⁺) showed a reduction in CEST contrast in 4% agarose gel (w/w) compared to that in buffered solutions, while the CEST effect for [Fe­(<b>L</b>)]²⁺ in 4% agarose gel (w/w) was not substantially different

Binding Modes of Carboxylate- and Acetylacetonate-Linked Chromophores to Homodisperse Polyoxotitanate Nanoclusters

The binding of carboxylate- and acetylacetonate-linked chromophores to homodisperse polyoxotitanate nanoclusters with 17 Ti atoms or more are surveyed and found to be limited to chelate-bidentate and the bridging modes, the former being dominant for the acetylacetonate-linked chromophores, the latter for the carboxylate linkers. Chromophores with acetylacetonate linking groups invariably bind in the chelate mode, whereas carboxylic acid terminated chromophores more frequently are observed to have the bridging mode, with the exception of three cases in which a strong electron-donating substituent is present on two different sensitizers. The calculations for isonicotinateand nitrophenylacetylacetonate functionalized Ti17 clusters show the observed binding modes to correspond to the lower energy functionalized clusters, but do not predict the difference between the cinnamic acid and dimethylaminocinnamic acid binding to Ti17, which are bridging and chelate respectively. Both binding modes were never observed to occur for a single chromophore, even when synthetic conditions were varied. Density of state calculations show broadening and splitting of the chromophore LUMO on complexation due to interaction with the cluster’s conduction band, as well as frequent penetration of sensitizer orbitals into the bandgap of the functionalized nanoparticle