Jordan M. Cox

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 CoII, FeII, and NiII complexes of 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (L) 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(L)]Cl2·2H2O or [Fe(L)](CF3SO3)2. The NiII complex [Ni(L)](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 N-(2-hydroxyethyl)piperazine-N′-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(L)]2+, [Ni(L)]2+, and [Fe(L)]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(L)]2+, which showed reduced CEST contrast in rabbit serum and egg white. The complexes with the least highly shifted CEST peaks ([Co(L)]2+ and [Ni(L)]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(L)]2+ in 4% agarose gel (w/w) was not substantially different.

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

Paramagnetic Fe(II) and Co(II) complexes are utilized as the first transition metal examples of (1)H NMR shift agents (paraSHIFT) for thermometry applications using Magnetic Resonance Spectroscopy (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. (1)H 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 (1)H NMR chemical shifts, integrated intensities, line widths, the distances obtained from X-ray diffraction measurements, and longitudinal relaxation time (T1) 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 (1)H 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 T1 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 T1 values suggests that these complexes, in particular the TMPC-based complexes, show promise as paraSHIFT agents for thermometry.

The role of atropisomers on the photo-reactivity and fatigue of diarylethene-based metal–organic frameworks

Photo-responsive metal–organic frameworks (MOFs) are one example of light controlled smart materials for use in advanced sensors, data storage, actuators and molecular switches. Herein we show the design, synthesis and characterization of a photo-responsive linker that is subsequently reacted to yield MOF single crystals. The photo-responsive properties of the resulting UBMOF-2 arise from the photo-induced cyclization of the diarylethene moiety designed into the linker. Computational modeling to assess the relative energies of linker atropisomers reveals a large energetic barrier preventing facile interconversion between key species. The role of this barrier on the observed photo-induced fatigue provides useful insight into the development of advanced photo-responsive nanoporous materials.

Six, Seven or Eight Coordinate Fe(II) , Co(II) or Ni(II) Complexes of Amide-Appended Tetraazamacrocycles for ParaCEST Thermometry.

Fe(II) , Co(II) and Ni(II) complexes of two tetraazamacrocycles (1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane (L1) and 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (L2) show promise as paraCEST agents for registration of temperature (paraCEST=paramagnetic chemical exchange saturation transfer). The Fe(II) , Co(II) and Ni(II) complexes of L1 show up to four CEST peaks shifted ≤112 ppm, whereas analogous complexes of L2 show only a single CEST peak at ≤69 ppm. Comparison of the temperature coefficients (CT ) of the CEST peaks of [Co(L2)](2+) , [Fe(L2)](2+) , [Ni(L1)](2+) and [Co(L1)](2+) showed that a CEST peak of [Co(L1)](2+) gave the largest CT (-0.66 ppm (o) C(-1) at 4.7 T). NMR spectral and CEST properties of these complexes correspond to coordination complex symmetry as shown by structural data. The [Ni(L1)](2+) and [Co(L1)](2+) complexes have a six-coordinate metal ion bound to the 1-, 4-amide oxygen atoms and four nitrogen atoms of the tetraazamacrocycle. The [Fe(L2)](2+) complex has an unusual eight-coordinate Fe(II) bound to four amide oxygen atoms and four macrocyclic nitrogen atoms. For [Co(L2)](2+) , one structure has seven-coordinate Co(II) with three bound amide pendents and a second structure has a six-coordinate Co(II) with two bound amide pendents.

A versatile environmental control cell for in situ guest exchange single-crystal diffraction

In situ single-crystal diffraction experiments provide researchers with the opportunity to study the response of crystalline systems, including metal–organic frameworks and other nanoporous materials, to changing local microenvironments. This paper reports a new environmental control cell that is remarkably easy to use, completely reusable, and capable of delivering static or dynamic vacuum, liquids or gases to a single-crystal sample. Furthermore the device is nearly identical in size to standard single-crystal mounts so a full unrestricted range of motion is expected for most commercial goniometers. In situ single-crystal X-ray diffraction experiments performed under dynamic gas-flow conditions revealed the cell was capable of stabilizing a novel metastable intermediate in the dehydration reaction of a previously reported metal–organic framework.

Polymorphism and the influence of crystal structure on the luminescence of the opto-electronic material 4,4′-bis(9-carbazolyl)biphenyl

Three polymorphs of 4,4′-bis(9-carbazolyl)biphenyl were prepared and characterized by X-ray diffraction and luminescence spectroscopy. Electronic structure calculations were performed to examine the influence of the molecular geometry on the HOMO and LUMO energy levels and calculated electronic transitions.

On the design of atropisomer-separable photochromic diarylethene-based metal–organic framework linkers

The relative stability and accessibility of atropisomers plays a prominent role in the efficacy of diarylethene-based photochromic materials. Herein, DFT methods, using the ωB97XD functional and a 6-31G(d) basis, are employed to determine the local energetic minima and maxima which describe the rotation of a thiophene group in derivatives of 9,10-bis(2-methyl-5-pheylthiophen-3-yl)phenanthrene-2,7-dicarboxylic acid, a photochromic linker molecule which exhibits atropisomer-formation-related fatigue when incorporated into a metal–organic framework. Results of these potential energy surface mapping calculations as well as their applications to atropisomer separability are discussed.

Structural response to desolvation in a pyridyl-phenanthrene diarylethene-based metal–organic framework

A phenanthrene-based diarylethene linker with linear pyridyl connectivity, 4,4′-(9,10-bis(2,5-dimethylthiophen-3-yl)phenanthrene-2,7-diyl)dipyridine linker (TPDPy) was prepared and subsequently used to synthesize an air-stable metal–organic framework, UBMOF-3 (Zn3(BDC)3(TPDPy)1(DMF)1.5, BDC = 1,4-benzenedicarboxylate, DMF = N,N-dimethylformamide). Upon irradiation with ultraviolet light, this photo-responsive framework, composed of terephthalate, TPDPy, and zinc pinwheels, exhibits strong linear dichroism consistent with the crystal structure. Activation (desolvation) of the crystal leads to a significant change in the crystal structure that improves the ability to crystallographically resolve the photochromic linker.

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

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

Photoactive and Physical Properties of an Azobenzene-Containing Coordination Framework*

A new three-dimensional coordination framework, [Zn4(tbazip)3(bpe)2(OH)2]·bpe·{solvent} (where bpe = 1,2-di(4-pyridyl)ethene) containing the novel photoactive ligand tbazip (tbazip = 5-((4-tert-butyl)phenylazo)isophthalic acid) has been synthesised and crystallographically characterised. The photoactivity of discrete tbazip was investigated and compared with its photoactivity while incorporated within the framework. The effect of isomerisation of the incorporated azobenzene on the chemical and physical properties of the framework were investigated using UV-vis and Raman spectroscopies. The framework is porous only to hydrogen gas at 77 K, but displayed an appreciable uptake for CO2 at 195 K.