Triphenylmethyl Research Articles

Inhibition of Glycosaminoglycan-Mediated Amyloid Formation by Islet Amyloid Polypeptide and proIAPP Processing Intermediates

Islet amyloid polypeptide (IAPP; also known as amylin) is responsible for islet amyloid formation in type 2 diabetes, and IAPP-induced toxicity is believed to contribute to the loss of β-cell mass associated with the late stages of type 2 diabetes. Islet amyloid formation may also play a role in graft failure after transplantation. IAPP is produced as a prohormone, pro-islet amyloid polypeptide (proIAPP), and processed in the secretory granules of the pancreatic β-cells. Partially processed forms of proIAPP are found in amyloid deposits; most notable is a 48-residue intermediate, proIAPP1–48, which includes the N-terminal pro-extension, but which has been properly processed at the C-terminus. Incomplete processing may play a role in islet amyloid formation by promoting interactions with sulfated proteoglycans of the extracellular matrix, which, in turn, promote amyloid formation. We show that acid fuchsin (3-(1-(4-amino-3-methyl-5-sulphonatophenyl)-1-(4-amino-3-sulphonatophenyl)methylene)cyclohexa-1,4-dienesulphonic acid), a simple sulfonated triphenyl methyl derivative, is a potent inhibitor of amyloid formation by the proIAPP1–48 intermediate. The more complicated triphenyl methane derivative fast green FCF {ethyl-[4-[[4-[ethyl-[(3-sulfophenyl)methyl]amino]phenyl]-(4-hydroxy-2-sulfophenyl)methylidene]-1-cyclohexa-2,5-dienylidene]-[(3-sulfophenyl)methyl]azanium} also inhibits amyloid formation by IAPP and the proIAPP processing intermediate. Both compounds inhibit amyloid formation by mixtures of the proIAPP intermediate and the model glycosaminoglycan heparan sulfate. Acid fuchsin also inhibits glycosaminoglycan-mediated amyloid formation by mature IAPP. The ability to inhibit amyloid formation is not simply due to the compounds being sulfonated, since the sulfonated inhibitor of amyloid-β, tramiprosate, is not an inhibitor of amyloid formation by proIAPP1–48.

Dynamic polarization of 13C nuclei in solid 13C labeled pyruvic acid

Dynamic nuclear polarization (DNP) has proved to be one of the most effective methods to increase the nuclear spin polarization in inorganic as well as organic materials since several decades. In combination with methods to rapidly dissolve the polarized solid sample it is possible to obtain a solution of molecules containing hyperpolarized nuclei. This has enabled new applications in Nuclear Magnetic Resonance (NMR) spectroscopy as well as medical applications in Magnetic Resonance Imaging (MRI). We studied the dynamic nuclear 13C polarization in solid [1- 13C] pyruvic acid doped with the trityl radical AH 111 501 at different temperatures and magnetic fields. The measurements were performed in a 4He evaporation refrigerator operated inside a superconducting solenoid system. Working points at temperatures between 900 and 1350 mK have been adjusted and the polarization measurements have been performed at magnetic fields of 2.5, 3.5 and 5 T, respectively. This set of measurements allows to draw a clear picture of the temperature and magnetic field dependency of the 13C polarization within the given range. The highest polarization measured was 74.7% at a temperature of 900 mK in a magnetic field of 5 T.

Multiparametric imaging of tumor oxygenation, redox status, and anatomical structure using overhauser-enhanced MRI-prepolarized MRI system

An integrated Overhauser-enhanced MRI-Prepolarized MRI system was developed to obtain radiobiological information that could be accurately coregistered with diagnostic quality anatomic images. EPR and NMR images were acquired through the double resonance technique and field cycling of the main magnetic field from 5 mT to 0.5 T. Dedicated EPR and NMR coils were devised to minimize radiofrequency power deposition with high signal-to-noise ratio. Trityl and nitroxide radicals were used to characterize oxygen and redox sensitivities of multispin echo Overhauser-enhanced MRI. Oxygen resolution of 3 mmHg was obtained from 2 mM deoxygenated trityl phantoms. Trityl radicals were stable in reducing environments and did not alter the redox-sensitive decaying rate of the nitroxide signals. Nitroxide radicals had a compounding effect for the trityl oximetry. Tumor oxygenation and redox status were acquired with anatomical images by injecting trityl and nitroxide probes subsequently in murine tumors. The Overhauser-enhanced MRI-Prepolarized MRI system is ready for quantitative longitudinal imaging studies of tumor hypoxia and redox status as radiotherapy prognostic factors.

Deconvolution of sinusoidal rapid EPR scans

In rapid scan EPR the magnetic field is scanned through the signal in a time that is short relative to electron spin relaxation times. Previously it was shown that the slow-scan lineshape could be recovered from triangular rapid scans by Fourier deconvolution. In this paper a general Fourier deconvolution method is described and demonstrated to recover the slow-scan lineshape from sinusoidal rapid scans. Since an analytical expression for the Fourier transform of the driving function for a sinusoidal scan was not readily apparent, a numerical method was developed to do the deconvolution. The slow scan EPR lineshapes recovered from rapid triangular and sinusoidal scans are in excellent agreement for lithium phthalocyanine, a trityl radical, and the nitroxyl radical, tempone. The availability of a method to deconvolute sinusoidal rapid scans makes it possible to scan faster than is feasible for triangular scans because of hardware limitations on triangular scans.

Synthesis, Structures, and Ethylene Polymerization Behavior of Bis(pyrazolyl)borate Zirconium and Hafnium Benzyl Complexes

The alkyl hydrido bis(pyrazolyl)borate reagent Tl(MeHB(3-mesitylpyrazolyl)2) (Tl(MeBpMs), 1) has been prepared and used to generate group 4 metal MeBpMs complexes. The reaction of 1 with ZrCl4 affords (MeBpMs*)2ZrCl2 (2, MeBpMs* = MeHB(3-mesitylpyrazolyl)(5-mesitylpyrazolyl)−). The reaction of 1 with M(CH2Ph)4 yields (MeBpMs)M(CH2Ph)3 (M = Zr (3), Hf (4)), bibenzyl, and Tl0, via initial MeBpMs/benzyl exchange to produce 3 or 4 and Tl(CH2Ph), followed by thermal decomposition of Tl(CH2Ph). The reaction of 3 with [Ph3C][B(C6F5)4] proceeds by one-electron oxidation of a zirconium benzyl bond to yield [(MeBpMs)Zr(CH2Ph)2][B(C6F5)4] (5) and a series of organic products derived from coupling and H atom transfer reactions of trityl and benzyl radicals. The reaction of 4 with [Ph3C][B(C6F5)4] yields [(MeBpMs)Hf(CH2Ph)2][B(C6F5)4] (6) along with Ph3CCH2Ph (86%) as the major organic product. The high yield of Ph3CCH2Ph in this reaction suggests that electrophilic benzyl abstraction competes with oxidative M−CH2Ph b...

ChemInform Abstract: The Triphenylmethyl Group - A Kinetically Stabilizing Substituent and Protecting Group in Organophosphorus Chemistry

The introduction of sterically demanding substituents at phosphorus leads to the protection of reactive centres, and consequently to the kinetic stabilization of molecules. Yoshifuji has demonstrat...

ChemInform Abstract: Novel Heterocyclic Analogues of Trityl Radicals: Synthesis and Dimerization of Diarylmethyl-1H-1,2,4-triazoles and Diarylmethyl-2H-phenanthro[9,10-d]-1,2,3-triazoles.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

TH‐D‐201C‐01: Advancing an Integrated Overhauser‐Enhanced MRI (OMRI) ‐ Prepolarized MM (PMRI) System Toward Quantitative Longitudinal Studies of Tumor Hypoxia and Redox Status

Purpose: To advance the imaging performance of an integrated Overhauser‐enhanced MRI (OMRI) ‐ prepolarized MRI (PMRI) system to enable quantitative longitudinal imaging studies of multi‐faceted tumor environment by using both electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) Method and Materials: A field‐cycled OMRI‐PMRI system was further developed to achieve the sensitivity that identifies radiobiological hypoxia and redox status. A dedicated 5‐cm saddle coil delivered 154‐MHz EPR radiofrequency (RF) pulses to induce the Overhauser effect with a high EPR B1 efficiency. A 3‐cm 5.5‐MHz NMR Litz‐wire saddle coil concentric to the EPR coil achieved high signal‐to‐noise ratio with an efficient filling factor. B0 was at 5 mT 0.13 T 0.5 T for EPR irradiation NMR readout NMR prepolarization respectively. Gradient echo and multi‐spin echo pulse sequences were implemented using a custom MRI console to acquire images with minimal phase distortion. Trityl phantoms were prepared under normoxic and anoxic environment for pO2 calibration. Various amounts of ascorbic acid (AsA) were injected to the mixtures of trityl and nitroxide (3‐carbamoyl PROXYL) phantoms to characterize the redox sensitivity. Results: Oxygen resolution of 4.1 torr and 3.5 torr were obtained from 4‐min double power (0.3 32 W) spin‐echo OMRI (TR/TE 1600/30 ms) for pure deoxygenated 1‐mM and 2‐mM trityl phantoms. Trityl radicals were not reduced by AsA and did not alter the reduction decay rate of the nitroxides (−0.07/min −0.13/min for 5 10‐mM AsA). Saturation factor measurements at various EPR RF power levels indicated a feasibility of accurate pO2 calibration for the mixtures of trityl and nitroxide radicals. Conclusion: Our OMRI‐PMRI system is capable of multi‐parametric imaging sensitive to pO2 redox status proton T1 and T2. The imager is ready to acquire physiological information in small animals accurately co‐registered with diagnostic quality anatomic NMR images.

Synthesis, structure, and EPR characterization of deuterated derivatives of Finland trityl radical

Substituted trityl radicals are important spin probes for functional electron paramagnetic resonance spectroscopy and imaging including oxygen and pH mapping in vivo. Here we report the synthetic procedure for large scale synthesis of deuterated Finland trityl radical with superior EPR spectral properties and higher sensitivity towards oxygen concentrations in solution. Additionally Finland trityl radicals substituted with linkers suitable for attaching peptide, or other synthetic precursors have been synthesized. The effect of deutero-substitution on EPR spectra of homologous derivatives has been evaluated. The compounds are potential candidates for targeted spin probes in EPR imaging.

Isolation of crystalline carbene-stabilized P2-radical cations and P2-dications

The discovery in 1900 by Gomberg that the trityl radical (Ph(3)C(.)) exists at room temperature is often considered to be the beginning of radical chemistry. Since then, persistent and even room-temperature stable radicals based on second-row and heavier elements have been synthesized. However, few of them have been characterized crystallographically, because they are either too reactive or dimerize in the solid state. Here, we show that a P(2) fragment, capped with two bulky, strongly electron-releasing singlet carbenes (dicoordinate carbon compounds with only six valence electrons), can undergo one-electron oxidation, giving rise to room-temperature stable radical cations. Moreover, when N-heterocyclic carbenes are used, two-electron oxidation can also be performed, producing the corresponding stable dicationic diphosphene, which has to be regarded as a P(2)(2+) fragment coordinated by two carbenes. These results reveal a new application of stable singlet carbenes, the stabilization of paramagnetic species and electron-poor fragments.

Metal-Radical Chains Based on Polychlorotriphenylmethyl Radicals: Synthesis, Structure, and Magnetic Properties

We report the synthesis, crystal structures, and magnetic properties of two new metal-radical chains built up from a new class of organic radical-based ligands, the polychlorinated triphenylmethyl (PTM) radicals. Crystal structures of two new 1D coordination polymers, [Cu(2)(PTMDC)(2)(py)(5)(EtOH)].3EtOH (1) and [Co(2)(PTMDC)(2)(DMF)(2)(H(2)O)(6)].5DMF (2) (where PTMDC is a PTM radical functionalized with two carboxylic groups), show similar chain-like structures, in which each of the PTMDC radicals are connecting two Cu(II) or Co(II) metal ions. Therefore, from a magnetic point of view, both structures describe a magnetic chain model based on the PTMDC-M(II) unit. In this manuscript, the magnetic exchange coupling constants between both metal ions and the bridging PTM radicals have been determined. In both cases, the temperature dependence of the magnetic susceptibility reveals antiferromagnetic exchange coupling constants between the PTMDC radicals and Cu(II) (J/k(B) = -42 K) and Co(II) (J/k(B) = -14.6 K) ions based on the exchange Hamiltonian H = -J sum S(A(i))S(A(i+1)).

Dynamic Nuclear Polarization with Polychlorotriphenylmethyl Radicals: Supramolecular Polarization-Transfer Effects

Ups and downs of DNP: Polychlorinated trityl radicals (see structure: C black, Cl green, Na gray, O red) used for dynamic nuclear polarization (DNP) showed a new transfer mechanism involving quadrupolar chlorine nuclei. The observation of positive or negative enhancements, depending on the substrate, highlights the supramolecular character of the initial polarization-transfer process.

Polychlorinated trityl radicals for dynamic nuclear polarization: the role of chlorine nuclei

Polychlorinated trityl radicals bearing carboxylate substituents are water soluble persistent radicals that can be used for dynamic nuclear polarization. In contrast to other trityl radicals, the polarization mechanism differs from the classical solid effect. DFT calculations performed to rationalize this behaviour support the hypothesis that polarization is transferred from the unpaired electron to chlorine nuclei and from these to carbon by spin diffusion. The marked differences observed between neutral and anionic forms of the radical will be discussed.

Finland Trityl Radical Derivatives with Enhanced Sensitivity to Tissue Oxygenation

Finland Trityl Radical Derivatives with Enhanced Sensitivity to Tissue Oxygenation

Design and synthesis of N-vinylacetamide derivative with bulky group by nucleophilic substitution reaction

Cyclohexyl, adamantyl, and triphenylmethyl groups were employed for the nucleophilic substitution reaction with N-vinylacetamide (NVA), in order to investigate the bulky substituents effects on molecular structures in N-vinyl monomers. Although normal alkyl halides were known to produce N-substituted NVA, alkyl halides with secondary and tertiary carbons did not occur nucleophilic substitution reaction. On the contrary, triphenylmethyl group was introduced into β-position on NVA, accompanied with hydrogen transfer. The refined crystal structure of β-triphenylmethyl-N-vinylacetamide revealed intermolecular linear hydrogen bonds and aromatic bulky triphenylmethyl group supported the structure.

Synthesis, Characterization, and Rotational Dynamics of Crystalline Molecular Compasses with N-Heterocyclic Rotators

We describe in this paper the synthesis, crystallization, and solid-state NMR dynamics of molecules intended to emulate the structure and function of macroscopic compasses. The desired structures consist of polar pyridine (2) and pyridazine (3) groups as well as their corresponding N-oxides (2O and 3O), each linked axially to two bulky triphenyl methyl groups by 1,4-triple bonds. The structures are such that the central polar heterocycles may rotate about the dialkyne axle while being sterically shielded by the two trityl groups. In addition to the synthesis of samples with natural isotopic abundance, we describe the preparation of 2-d(2) and 3-d(30), one labeled with deuteria in the pyridine rotator and the other fully deuterated in the two trityl groups in the stator. Crystal structures of 2 and 3 revealed packing motifs analogous to those previously reported for samples prepared with substituted phenylene rotators. While solid-state NMR measurements by (13)C CPMAS NMR revealed insufficient chemical shift dispersion for a dynamic characterization of the rotation of compounds 2 and 3 (including 3-d(30)), the use of quadrupolar echo (2)H NMR methods with 2-d(2) revealed a rotational site exchange with a barrier of ca. 8.5 kcal/mol (35.5 kJ mol(-1)) for the pyridine group in 2.

Synthesis and properties of [4-(triphenylmethyl)phenoxy]acetic and 3-[4-(triphenylmethyl)phenoxy]propionic acids and their condensation with phthalimide leading to meso-substituted tetrabenzoporphyrins

Condensation of 4-(triphenylmethyl)phenol with monochloroacetic and 3-bromopropionic acids gave, respectively, [4-(triphenylmethyl)phenoxy]acetic and 3-[4-(triphenylmethyl)phenoxy]propionic acids which reacted with phthalimide in the presence of zinc acetate to produce meso-substituted zinc tetrabenzoporphyrins having bulky triphenylmethyl groups in the substituent. The corresponding free ligands were obtained by demetalation of the zinc complexes. Spectral properties of the synthesized compounds were studied.

Formation of Ammonia from an Iron Nitrido Complex

Radical ideas: Reaction of the iron(IV) nitrido complex [PhB(MesIm)(3)Fe[triple chemical bond]N] (see picture, Mes=2,4,6-Me(3)C(6)H(2)) with TEMPO-H (1-hydroxy-2,2,6,6-tetramethylpiperidine) results in high yields of ammonia and quantitative formation of [PhB(MesIm)(3)Fe(tempo)]. The mechanism likely involves hydrogen-atom transfer from TEMPO-H to the nitrido complex. Similar reaction with the triphenylmethyl radical yields [PhB(MesIm)(3)Fe[triple chemical bond]N--CPh(3)].

Thermomagnetic properties of the Finland trityl radical

The Finland trityl paramagnet is characterized by magnetic susceptibility and a new form of quantitative electron paramagnetic resonance (EPR) that utilizes a superconducting quantum interference device (SQUID) as a detection method. This radical is of interest due to its use as a dynamic nuclear polarization agent as well as a potential magnetic refrigerant and quantum computing bit. The SQUID-EPR data show that the EPR linewidth of a concentrated trityl powder decreases dramatically from 4.4 to 1.4 mT as the temperature is increased from 1.8 to 10 K. The quantitative nature of SQUID-EPR is used to thermodynamically quantify the EPR energy transfer times and saturated fractions. At 95 GHz and 1.8 K, only 40% of the spins are in resonance at the onset of saturation. Conventional dc magnetic susceptibility over 1.8-150 K indicates an S=12 Curie-Weiss relationship with little long range interaction. Magnetization versus applied field at 1.8 and 4 K fits a Brillouin function with >80% electronic polarization at a normalized field of gmu(B)mu(0)HkT approximately 3. These results provide information required for theoretical modeling and engineering of the trityl radical for a wide range of applications.

Synthesis and Polymerization of Bismaleimide Derived from 5(6)-amino-1(4′-aminophenyl)-1,3,3′-trimethyl indane

The acid-catalyzed dimerization of α-methyl styrene led to the formation of trimethyl phenyl indane, which on nitration followed by reduction using hydrazine hydrate gave 5(6)-amino-1(4′-aminophenyl)-1,3,3′-trimethyl indane. This aromatic diamine was used to synthesize bismaleamic acid and imidized to yield bismaleimide. The bismaleamic acid was converted to prepolymer directly by imidizing it in refluxing toluene. All the materials synthesized were characterized using FTIR, 1H and 13C NMR. The direct inlet mass spectral characterizations were carried out for bismaleamic acid, bismaleimide and bismaleimide prepolymer. The fragmentation pattern was discussed in detail and the structure proposed was confirmed. The thermogravimetric studies were done for all the materials and kinetic parameters (energy of activation and frequency factor) were calculated using Dharwadkar and Kharkhanavala method. The structural changes occurring in the thermally polymerized bismaleimide and bismaleimide prepolymer were discussed.