Triphenylmethyl Research Articles

Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency.

In vivo oximetry by pulsed electron paramagnetic resonance is based on measurements of changes in electron spin relaxation rates of probe molecules, such as the triarylmethyl radicals. A series of experiments was performed at frequencies between 250 MHz and 1.5 GHz to assist in the selection of an optimum frequency for oximetry. Electron spin relaxation rates for the triarylmethyl radical OX063 as a function of radical concentration, salt concentration, and resonance frequency were measured by electron spin echo 2-pulse decay and 3-pulse inversion recovery in the frequency range of 250 MHz-1.5 GHz. At constant OX063 concentration, 1/T1 decreases with increasing frequency because the tumbling dependent processes that dominate relaxation at 250 MHz are less effective at higher frequency. 1/T2 also decreases with increasing frequency because 1/T1 is a significant contribution to 1/T2 for trityl radicals in fluid solution. 1/T2-1/T1, the incomplete motional averaging contribution to 1/T2, increases with increasing frequency. At constant frequency, relaxation rates increase with increasing radical concentration due to contributions from collisions that are more effective for 1/T2 than 1/T1. The collisional contribution to relaxation increases as the concentration of counter-ions in solution increases, which is attributed to interactions of cations with the negatively charged radicals that decrease repulsion between trityl radicals. The Signal-to-Noise ratio (S/N) of field-swept echo-detected spectra of OX063 were measured in the frequency range of 400 MHz-1 GHz. S/N values, normalized by √Q, increase as frequency increases. Adding salt to the radical solution decreased S/N because salt lowers the resonator Q. Changing the temperature from 19 to 37 °C caused little change in S/N at 700 MHz. Both slower relaxation rates and higher S/N at higher frequencies are advantageous for oximetry. The potential disadvantage of higher frequencies is the decreased depth of penetration into tissue.

Trityl radicals in perfluorocarbon emulsions as stable, sensitive, and biocompatible oximetry probes

EPR oximetry with the use of trityl radicals can enable sensitive O2 measurement in biological cells and tissues. However, in vitro cellular and in vivo biological applications are limited by rapid trityl probe degradation or biological clearance and the need to enhance probe O2 sensitivity. We synthesized novel perfluorocarbon (PFC) emulsions, ∼200nm droplet size, containing esterified perchlorinated triphenyl methyl (PTM) radicals dispersed in physiological aqueous buffers. These formulations exhibit excellent EPR signal stability, over 20-fold greater than free PTM probes, with high oxygen sensitivity ∼17mG/mmHg enabling pO2 measurement in aqueous solutions or cell suspensions with sensitivity >0.5mmHg. Thus, PFC-PTM probes hold great promise to enable combined O2 delivery and sensing as needed to restore or enhance tissue oxygenation in disease.

Structure–performance landscape of N-alkoxyphthalimides as organocatalysts in aerobic oxidation

N-Alkoxyphthalimides were studied to design new-type organocatalysts for aerobic oxidation that are capable of metal/initiator-freely forming both phthalimide N-oxyl radicals and alkyl radicals in situ via their light/heat-induced homolysis. Our results show that their >NO–C bond strengths and HOMO-LUMO gaps change greatly upon altering N-alkoxy groups, which greatly decrease when their N-alkoxy groups include steric fluorenyl, xanthenyloxy, or triphenylmethyl groups. The conventional substituents on the bilateral phenyl rings of N-benzyloxyphthalimide have negligible effects on their >NO–C bond strengths, but significantly tune their HOMO-LUMO gaps. The photochemical activity of N-benzyloxy-4-aminophthalimide and N-4-amino-benzyloxyphthalimide may be similar to that of known N-triphenylmethyloxyphthalimide and N-diphenylmethyloxyphthalimide. Both the thermal and photochemical stability of N-acetyloxyphthalimides are higher than those of N-alkoxyphthalimides, but their hydrolysis to form N-hydroxyphthalimide is more favorable. The present work allows a reasonable prediction of the catalytic performance of N-alkoxyphthalimides and provides a new perspective for the rational design of organocatalysts for industrial applications.

Strong Evidence of a Phosphanoxyl Complex: Formation, Bonding, and Reactivity of Ligated Phosphorus Analogues of Nitroxides.

Facile access to [W(CO)5 (Ph2 P-OTEMP)] is used to initiate a study on the generation, properties, and reactions of transient phosphanoxyl complexes [MLn (R2 PO)], the first example of which could be trapped via heterocoupling with the trityl radical. It is also demonstrated that the phosphorus nitroxyl complex acts as radical initiator in the polymerization of styrene. The quest for P-O versus O-N bond homolysis, as well as the initial steps of the polymerization were studied by DFT methods.

Synthesis and characterization of regioselectively substituted curdlan hetero esters via an unexpected acyl migration

Regioselectively substituted curdlan esters were synthesized by protecting the C6 primary hydroxyl group with a triphenylmethyl group followed by the acylation of the secondary hydroxyl groups at C2 and C4. The subsequent detritylation of C6 trityl group under acidic conditions revealed an unexpected acyl migration from C4 to C6. This unique acyl migration in curdlan was first observed, which haven⿿t been reported in other polysaccharides such as cellulose. The rate of this migration was found to be dependent on the length of the acyl group, leading to the proposal of a new mechanism for this transformation. Based on these results, we synthesized 2,6-di-O-acetyl-4-O-propionyl-curdlan, which was fully characterized by 1H NMR, 13C NMR, COSY, HSQC and HMBC analyses. Thermogravimetric analysis and differential scanning calorimetry measurements revealed that the regioselective esterification to curdlan promoted its crystallization compared with randomly mixed ester derivatives.

In vivo EPR extracellular pH-metry in tumors using a triphosphonated trityl radical

The ability to assess the extracellular pH (pHe) is an important issue in oncology, because extracellular acidification is associated with tumor aggressiveness and resistance to cytotoxic therapies. In this study, a stable triphosphonated triarylmethyl (TPTAM) radical was qualified as a pHe electron paramagnetic resonance (EPR) molecular reporter. Calibration of hyperfine splitting as a function of pH was performed using a 1.2-GHz EPR spectrometer. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was used as an extracellular paramagnetic broadening agent to assess the localization of TPTAM when incubated with cells. In vivo EPR pH-metry was performed in MDA, SiHa, and TLT tumor models and in muscle. Bicarbonate therapy was used to modulate the tumor pHe. EPR measurements were compared with microelectrode readouts. The hyperfine splitting of TPTAM was strongly pH-dependent around the pKa of the probe (pKa = 6.99). Experiments with Gd-DTPA demonstrated that TPTAM remained in the extracellular compartment. pHe was found to be more acidic in the MDA, SiHa, and TLT tumor models compared with muscle. Treatment of animals by bicarbonate induced an increase in pHe in tumors: similar variations in pHe were found when using in vivo EPR or invasive microelectrodes measurements. This study demonstrates the potential usefulness of TPTAM for monitoring pHe in tumors. Magn Reson Med 77:2438-2443, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Comparison of ionic liquids and deep eutectic solvents as additives for the ultrasonic extraction of astaxanthin from marine plants

Astaxanthin is a carotenoid that is used widely in salmonid and crustacean aquaculture to provide the pink color characteristics of that species. Ionic liquids and deep eutectic solvents have attracted considerable attention for their potential in green chemistry. In this study, ionic liquids and deep eutectic solvents were used as additives for the extraction of astaxanthin. The optimal DES was synthesized from methyl triphenyl phosphonium bromide and 1,2-butanediol (1:4) mixed at 130°C. The optimal conditions for the extraction of astaxanthin were 1g solid sample, 40mL acetone and 0.25mg/mL of [EMIM][Br] or 0.25mg/mL DES-19 as an additive with 65W ultra-sonication at 90min. Under the extraction conditions using 0.25mg/mL of [EMIM][Br] or 0.25mg/mL DES-19 additives, 47.30μg/g or 73.49μg/g astaxanthin, respectively, were extracted from Portunus trituberculatus waste.

Epr Spectroscopy Of Trityl Radicals: Specificities Of Hyperfine Interaction Of An Unpaired Electron With 13c Nuclei

The constants of hyperfine coupling between an unpaired electron and natural occurrence 13C have been registered for the representative series of trityl radicals. The analysis of hyperfine ac constantsrevealed their small if any dependence both on solvent, and origin and number of substituents attached at para-C atoms of TAM aromatic rings.

DNP with Trityl Radicals in Deuterated Polyethylene

Chemically doping with trityl radicals was performed in fully deuterated polyethylene. The behavior of paramagnetic centers has been investigated by ESR X-band spectrometer. The highest deuteron polarization was 8% at 2.5 T and 1 K with a spin concentration of [Formula: see text] spins/g.

Paramagnetic spherical nanoparticles by the self-assembly of persistent trityl radicals.

Spherical nanoparticles and fibres observable by cryo-electron microscopy are spontaneously formed by the Finland trityl radical at concentrations above 15 mM. These species represent a new class of paramagnetic, metal-free, nanoscale supramolecular materials. Self-association was observed under a variety of experimental conditions, including aqueous solution at room temperature, low temperature frozen glasses and the gas phase. Oligomers formed by at least 5 Finland radicals were detected by ion-mobility mass spectrometry. Magnetic susceptibility data as well as low temperature EPR spectra show coupling between electronic spins in the self-assembled species. Quantum chemical calculations show stacking along the C3 symmetry axis. Nanoparticle formation requires additional lateral packing that can be provided by hydrogen bonding involving the triangular array of carboxylic acid groups leading to the assembly of geodesic spheres.

Electron spin dynamics and spin-lattice relaxation of trityl radicals in frozen solutions.

Electron spin-lattice relaxation of two trityl radicals, d24-OX063 and Finland trityl, were studied under conditions relevant to their use in dissolution dynamic nuclear polarization (DNP). The dependence of relaxation kinetics on temperature up to 100 K and on concentration up to 60 mM was obtained at X- and W-bands (0.35 and 3.5 Tesla, respectively). The relaxation is quite similar at both bands and for both trityl radicals. At concentrations typical for DNP, relaxation is mediated by excitation transfer and spin-diffusion to fast-relaxing centers identified as triads of trityl radicals that spontaneously form in the frozen samples. These centers relax by an Orbach-Aminov mechanism and determine the relaxation, saturation and electron spin dynamics during DNP.

Trityl-based alkoxyamines as NMP controllers and spin-labels.

Recently, new applications of trityl-nitroxide biradicals were proposed. In the present study, attachment of a trityl radical to alkoxyamines was performed for the first time. The rate constants kd of C-ON bond homolysis in these alkoxyamines were measured and found to be equal to those for alkoxyamines without trityl. The electron paramagnetic resonance (EPR) spectra of the products of alkoxyamine homolysis (trityl-TEMPO and trityl-SG1 biradicals) were recorded, and the corresponding exchange interactions were estimated. The decomposition of trityl-alkoxyamine showed more than an 80% yield of biradicals, meaning that the C-ON bond homolysis is the main reaction. The suitability of these labelled initiators/controllers for polymerisation was exemplified by means of successful nitroxide-mediated polymerisation (NMP) of styrene. Thus, this is the first report of a spin-labelled alkoxyamine suitable for NMP.

Pulsed Dynamic Nuclear Polarization with Trityl Radicals.

Continuous-wave (CW) dynamic nuclear polarization (DNP) is now established as a method of choice to enhance the sensitivity in a variety of NMR experiments. Nevertheless, there remains a need for the development of more efficient methods to transfer polarization from electrons to nuclei. Of particular interest are pulsed DNP methods because they enable a rapid and efficient polarization transfer that, in contrast with CW DNP methods, is not attenuated at high magnetic fields. Here we report nuclear spin orientation via electron spin-locking (NOVEL) experiments using the polarizing agent trityl OX063 in glycerol/water at a temperature of 80 K and a magnetic field of 0.34 T. (1)H NMR signal enhancements up to 430 are observed, and the buildup of the local polarization occurs in a few hundred nanoseconds. Thus, NOVEL can efficiently dynamically polarize (1)H atoms in a system that is of general interest to the solid-state DNP NMR community. This is a first, important step toward the general application of pulsed DNP at higher fields.

Glycerol-based deep eutectic solvents: Physical properties

Deep eutectic solvents (DESs) have been used in many industrial applications. DES is a mixture of a salt and a hydrogen bond donor (HBD). In this study, 70 DESs were synthesized successfully based on glycerol (Gly) as the HBD with different phosphonium and ammonium salts, namely methyl triphenyl phosphonium bromide (MTPB), benzyl triphenyl phosphonium chloride (BTPC), allyl triphenyl phosphonium bromide (ATPB), choline chloride (ChCl), N,N-diethylethanolammonium chloride (DAC), and tetra-n-butylammonium bromide (TBAB). The DESs were prepared using different molar ratios of the HBD to the salts. The freezing point of each DES was determined using Differential Scanning Calorimetry (DSC). The physical properties of these DESs, including density, viscosity, conductivity, and surface tension, were investigated as functions of temperature. In addition, the functional groups were analyzed utilizing Fourier transform infrared (FTIR) spectroscopy. It is worth noting that these systems have a wide variety of physical properties, which implies that these DESs would be suitable for diverse applications.

Intramolecular Addition of Triarylmethanes to Alkynes Promoted by KOtBu/DMF: A Synthetic Approach to Indene Derivatives

AbstractA method for the intramolecular addition of triarylmethanes to alkynes has been developed. The reaction was efficiently promoted by KOtBu/DMF without any transition‐metal catalyst. A variety of indene derivatives were prepared in moderate to good yields. A cascade cyclization of 2‐alkyl‐substituted substrates at elevated reaction temperature gave bicyclic indene derivatives. The reaction is proposed to proceed through the generation of a triphenylmethyl radical.

Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity

Due to their toxicity and persistence in the environment, brominated flame retardants (BFRs) are being phased out of commercial use, leading to the increased use of alternative chemicals such as the organophosphorus flame retardants (OPFRs). There is, however, limited information on the potential health effects of OPFRs. Due to the structural similarity of the OPFRs to organophosphorus insecticides, there is concern regarding developmental toxicity and neurotoxicity. In response, we evaluated a set of OPFRs (triphenyl phosphate [TPHP]), isopropylated phenyl phosphate [IPP], 2-ethylhexyl diphenyl phosphate [EHDP], tert-butylated phenyl diphenyl phosphate [BPDP], trimethyl phenyl phosphate [TMPP], isodecyl diphenyl phosphate [IDDP], (tris(1,3-dichloroisopropyl) phosphate [TDCIPP], and tris(2-chloroethyl)phosphate [TCEP]) in a battery of cell-based in vitro assays and alternative model organisms and compared the results to those obtained for two classical BFRs (3,3′,5,5′-tetrabromobisphenol A [TBBPA] and 2,2′4,4′-brominated diphenyl ether [BDE-47]). The assays used evaluated the effects of chemicals on the differentiation of mouse embryonic stem cells, the proliferation and growth of human neural stem cells, rat neuronal growth and network activity, and development of nematode (Caenorhabditis elegans) and zebrafish (Danio rerio). All assays were performed in a concentration-response format, allowing for the determination of the point of departure (POD: the lowest concentration where a chemically-induced response exceeds background noise). The majority of OPFRs (8/9) were active in multiple assays in the range of 1–10μM, most of which had comparable activity to the BFRs TBBPA and BDE-47. TCEP was negative in all assays. The results indicate that the replacement OPFRs, with the exception of TCEP, showed comparable activity to the two BFRs in the assays tested. Based on these results, more comprehensive studies are warranted to further characterize the potential hazard of some of these OPFR compounds.

Efficient Dynamic Nuclear Polarization at 800 MHz/527 GHz with Trityl‐Nitroxide Biradicals

AbstractCross‐effect (CE) dynamic nuclear polarization (DNP) is a rapidly developing technique that enhances the signal intensities in magic‐angle spinning (MAS) NMR spectra. We report CE DNP experiments at 211, 600, and 800 MHz using a new series of biradical polarizing agents referred to as TEMTriPols, in which a nitroxide (TEMPO) and a trityl radical are chemically tethered. The TEMTriPol molecule with the optimal performance yields a record 1H NMR signal enhancement of 65 at 800 MHz at a concentration of 10 mM in a glycerol/water solvent matrix. The CE DNP enhancement for the TEMTriPol biradicals does not decrease as the magnetic field is increased in the manner usually observed for bis‐nitroxides. Instead, the relatively strong exchange interaction between the trityl and nitroxide moieties determines the magnetic field at which the optimum enhancement is observed.

Efficient Dynamic Nuclear Polarization at 800 MHz/527 GHz with Trityl-Nitroxide Biradicals.

Cross-effect (CE) dynamic nuclear polarization (DNP) is a rapidly developing technique that enhances the signal intensities in magic-angle spinning (MAS) NMR spectra. We report CE DNP experiments at 211, 600, and 800 MHz using a new series of biradical polarizing agents referred to as TEMTriPols, in which a nitroxide (TEMPO) and a trityl radical are chemically tethered. The TEMTriPol molecule with the optimal performance yields a record (1) H NMR signal enhancement of 65 at 800 MHz at a concentration of 10 mM in a glycerol/water solvent matrix. The CE DNP enhancement for the TEMTriPol biradicals does not decrease as the magnetic field is increased in the manner usually observed for bis-nitroxides. Instead, the relatively strong exchange interaction between the trityl and nitroxide moieties determines the magnetic field at which the optimum enhancement is observed.

Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives—A Study To Advance Their Applicability as in Vivo EPR Oxygen Sensors.

Tissue oxygenation plays an important role in the pathophysiology of various diseases and is often a marker of prognosis and therapeutic response. EPR (ESR) is a suitable noninvasive oximetry technique. However, to reliably deploy soluble EPR probes as oxygen sensors in complex biological systems, there is still a need to investigate and improve their specificity, sensitivity, and stability. We reproducibly synthesized various derivatives of tetrathiatriarylmethyl and tetrachlorotriarylmethyl (trityl) radicals. Hydrophilic radicals were investigated in aqueous solution mimicking physiological conditions by, e.g., variation of viscosity and ionic strength. Their specificity was satisfactory, but the oxygen sensitivity was low. To enhance the capability of trityl radicals as oxygen sensors, encapsulation into oily core nanocapsules was performed. Thus, different lipophilic triesters were prepared and characterized in oily solution employing oils typically used in drug formulations, i.e., middle-chain triglycerides and isopropyl myristate. Our screening identified the deuterated ethyl ester of D-TAM (radical 13) to be suitable. It had an extremely narrow single EPR line under anoxic conditions and excellent oxygen sensitivity. After encapsulation, it retained its oxygen responsiveness and was protected against reduction by ascorbic acid. These biocompatible and highly sensitive nanosensors offer great potential for future EPR oximetry applications in preclinical research.

Room-Temperature Electron Spin Relaxation of Triarylmethyl Radicals at the X- and Q-Bands.

Triarylmethyl radicals (trityls, TAMs) represent a relatively new class of spin labels. The long relaxation of trityls at room temperature in liquid solutions makes them a promising alternative for traditional nitroxides. In this work we have synthesized a series of TAMs including perdeuterated Finland trityl (D36 form), mono-, di-, and triester derivatives of Finland-D36 trityl, the deuterated form of OX63, the dodeca-n-butyl homologue of Finland trityl, and triamide derivatives of Finland trityl with primary and secondary amines attached. We have studied room-temperature relaxation properties of these TAMs in liquids using pulsed electron paramagnetic resonance (EPR) at two microwave frequency bands. We have found the clear dependence of phase memory time (Tm ∼ T2) on the magnetic field: room-temperature Tm values are ∼1.5-2.5 times smaller at the Q-band (34 GHz, 1.2 T) than at the X-band (9 GHz, 0.3 T). This trend is ascribed to the contribution from g-anisotropy that is negligible at lower magnetic fields but comes into play at the Q-band. In agreement with this, the difference between T1 and Tm becomes more pronounced at the Q-band than at the X-band due to increased contributions from incomplete motional averaging of g-anisotropy. Linear dependence of (1/Tm - 1/T1) on viscosity implies that g-anisotropy is modulated by rotational motion of the trityl radical. On the basis of the analysis of previous data and results of the present work, we conclude that, in the general situation where the spin label is at least partly mobile, the X-band is most suitable for application of trityls for room-temperature pulsed EPR distance measurements.