Quantitative applications of ¹H and ³¹P chemically induced dynamic nuclear polarization

Chemically Induced Dynamic Nuclear Polarization (CIDNP) spectroscopy has been widely used for many years for study of mechanisms of reactions that involve free radical pairs. Unlike Electron Spin Resonance (ESR) spectroscopy CIDNP provides an information on radicals that have been already reacted to paramagnetic species bringing the power of NMR into determination and identification of reaction pathways, yields and environmental effects. Since been discovered in year 1969 CIDNP was mostly applied in purely qualitative mechanistic studies where the simple rules developed by Kaptein allowed to deduce number of important reaction parameters. The quantitative application of CIDNP was rather difficult since there were sometimes no other experimental evidence to be compared especially within the cases where ESR failed. With the fast development of different theoretical calculation procedures which can provide rather precise knowledge on geometry, electron spin distribution and various magnetic properties of free radicals(g-factors, hyperfine coupling constants), CIDNP finds a new broad field of use especially where other physico-chemical methods are not successful by different reasons. Being a variety of Nuclear Magnetic Resonance (NMR) spectroscopy CIDNP is limited by the same drawbacks - bad time resolution (usually microseconds) and poor sensitivity. Despite that it can follow the radical processes that are by far too fast to be observed ESR spectroscopy - the most straightforward method to observe free radicals. The rate of fastest radical reactions that can be observed by CIDNP is determined by the rate of intersystem crossing which is about 10−10 −10−9s. The information on free radical properties and properties of the paramagnetic products of the reaction is then stored within the longitudinal relaxation time of the particular nuclei which is typically 1 - 10s. That very important information includes spin distribution, radical concentration, rotation diffusion and magnetic properties of radicals and rates of reactions. Within the certain conditions it can be extracted by the analysis of CIDNP spectra. The two different novel quantitative and semiquantitative applications of Chemically Induced Dynamic Nuclear Polarization combined with density functional quantum mechanical calculations and NMR studies are the subject of the present thesis. First application is of almost pure fundamental interest whereas the second finds its use in industry

Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton

[EN] Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.This work was supported by the Carlos III Institute of Health (Grants No. PII6/01877, "Miguel Servet fellowship" CPII16/00052 to I.A.), and by the Generalitat Valenciana (Prometeo 2017/075). We would like to thank Dr Fedora Grande for sending an exchange student (M.B.). D.N. and G.G. thank NAWI Graz for support.Palumbo, F.; Andreu Ros, MI.; Brunetti, M.; Schmallegger, M.; Gescheidt, G.; Neshchadin, D.; Miranda Alonso, MÁ. (2019). Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton. The Journal of Organic Chemistry. 84(23):15184-15191. https://doi.org/10.1021/acs.joc.9b02181S15184151918423Zerbinati, C., & Iuliano, L. (2017). 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Paramagnetic Molecular Grippers: The Elements of Six-State Redox Switches

The development of semiquinone-based resorcin[4]arene cavitands expands the toolbox of switchable molecular grippers by introducing the first paramagnetic representatives. The semiquinone (SQ) states were generated electrochemically, chemically, and photochemically. We analyzed their electronic, conformational, and binding properties by cyclic voltammetry, ultraviolet/visible (UV/vis) spectroelectrochemistry, electron paramagnetic resonance (EPR) and transient absorption spectroscopy, in conjunction with density functional theory (DFT) calculations. The utility of UV/vis spectroelectrochemistry and EPR spectroscopy in evaluating the conformational features of resorcin[4]arene cavitands is demonstrated. Guest binding properties were found to be enhanced in the SQ state as compared to the quinone (Q) or the hydroquinone (HQ) states of the cavitands. Thus, these paramagnetic SQ intermediates open the way to six-state redox switches provided by two conformations (open and closed) in three redox states (Q, SQ, and HQ) possessing distinct binding ability. The switchable magnetic properties of these molecular grippers and their responsiveness to electrical stimuli has the potential for development of efficient molecular devices

Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls

The aim of the present paper is to explore the potential of radical-mediated dehydrogenation of bile salts (BSs), which is reminiscent of the enzymatic action of hydroxysteroid dehydrogenase enzymes (HSDH). The concept has been demonstrated using triplet carbonyls that can be efficiently generated upon selective UVA-excitation. Hydrogen atom transfer (HAT) from BSs to triplet benzophenone (BP) derivatives gave rise to radicals, ultimately leading to reduction of the BP chromophore with concomitant formation of the oxo-analogs of the corresponding BSs. The direct reactivity of triplet BP with BSs in the initial step was evaluated by determining the kinetic rate constants using laser flash photolysis (LFP). The BP triplet decay was monitored (lambda(max) = 520 nm) upon addition of increasing BS concentrations, and the obtained rate constant values indicated a reactivity of the methine hydrogen atoms in the order of C-3 < C-12 < C-7. The steady-state kinetics of the overall process, monitored through the disappearance of the typical BP absorption band at 260 nm, was much faster under N-2 than under O-2, also supporting the role of the oxygen-quenchable triplet in the dehydrogenation process. Furthermore, irradiation of deaerated aqueous solutions of sodium cholate in the presence of KPMe provided the oxo-analogs, 3[O], 7[O]-CA, 3[O]-CA and 7[O]-CA, arising from the HAT process.Financial support from the Spanish Government (Grants SEV-2012-0267 and CTQ2012-38754-C03-03), Generalitat Valenciana (Prometeo Program) and the Technical University of Valencia (Predoctoral FPI fellowship for P. Miro) is gratefully acknowledged.Miró Richart, P.; Marín García, ML.; Miranda Alonso, MÁ. (2016). Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls. Organic and Biomolecular Chemistry. 14(9):2679-2683. https://doi.org/10.1039/c5ob02561cS2679268314

Schmitt Trigger Using a Self-Healing Ionic Liquid Gated Transistor

Electrical double layer transistors using ionic liquids as the gate and ZnO as the semiconductor exhibit stable operation in the presence of redox active additives. The characteristics of the device enable single components with the response of a Schmitt trigger

Structure-Property Relationships of Organic Fused Conjugated Polymers

This work is devoted to the rational design of conjugated polymers for optoelectronic applications. I have synthesized and studied structure-property relationships in cationic polymers for electrochromic applications and “ladder” polymers for organic light emitting transistors. Cationic conjugated polymers are widely used as sensors, electrochromic materials and interfacial layers. However, most of them rely on charged side chains. To satisfy the unmet need in new classes of conjugated polymers with positive charges incorporated into the π-system, we designed a new positively charged monomer with a fused pyridine ring. Based on this motif, we have synthesized a series of conjugated cationic polymers by Stille polycondensation. Through iterative design and side-chain engineering we improved solubility and electrochemical stability of these materials and found that they exhibit red-green electrochromism. Counterion optimization decreases switching time and opens new opportunities for design of electrochromic materials. Organic light emitting transistors combine light emission and transistor control in one device. OLET materials must exhibit efficient luminescence, high ambipolar mobility and excellent processability. However, these properties are at odds with each other – π-π stacking benefits charge transport, but decreases luminescence. To solve this issue we designed and synthesized a series of “twisted” conjugated polymers that can be continuously cyclized by oxidation to provide “ladder” type polymers with fused rings in the main chain. Using this approach we found a partially cyclized polymer that is best for light emission due to balance between charge transport and quenching of luminescence in solid state. Oxidative cyclization allows to gradually tune optical and electronic properties of synthesized materials for improved OLET performance

The Year 1999: An Attempt at Political Forecasting

Political events will to a considerable degree predominate over economics in 1999, although the economic crisis, in turn, will affect the course of the political election races, imposing on them certain constraints beyond which no political force will be able to go. If we view the crisis of 1998-99 as a systemic (and cyclical) one, it can be said that unless a number of political and governmental problems are solved, it will be impossible to overcome the economic crisis, and that the state of the Russian economy will impede the adoption of various political and governmental decisions.

UV-triggered end group conversion of photo-initiated poly(methyl methacrylate)

The analysis of photo-initiated poly(methyl methacrylate) via electrospray ionization-mass spectrometry (ESI-MS) (synthesized by pulsed laser polymerization (PLP, at λ = 351 nm) of methyl methacrylate (MMA) and benzoin as photoinitiator at 6 mJ/pulse laser energy) evidences the presence of unidentified species. The determination of the origin of these species requires a detailed investigation via size exclusion chromatography-electrospray ionization-mass spectrometry (SEC/ESI-MS) and chemically induced dynamic nuclear polarization-nuclear magnetic resonance spectroscopy (CIDNP-NMR). It was found that post-irradiation of benzoin-initiated poly(methyl methacrylate) leads to α-cleavage of the benzoyl fragment leading to a sequence of cascade reactions, including the formation of an additional double bond within the polymer chain as evidenced via ESI-MS. Furthermore, the reaction products of the benzoyl radical post α-cleavage (e.g., benzaldehyde, phenyl methyl ketone, methyl formate, or methane) as well as the formed macroradical can be followed by CIDNP-NMR, which allows establishing a reaction mechanism for the UV-induced cleavage process. The study thus evidence that-if the integrity of UV initiated polymers is to be kept intact during their synthesis-very low irradiation energies need to be employed. © 2012 American Chemical Society

Time-Resolved EPR as a Tool to Investigate Oxygen Quenching in Photoinitiated Radical Polymerizations

It is challenging to obtain absolute rate constants for the quenching of organic radicals by molecular oxygen because they often do not present absorbance in the UV–vis range. Here, it is shown that time-resolved EPR (chemically induced dynamic electron polarization, or CIDEP) spectroscopy is useful in establishing rate constants for the addition of benzoyl radicals to molecular oxygen. It was found that benzoyl radicals are particularly reactive toward O₂ and can, therefore, act as oxygen scavengers in the initiating phase of radical polymerizations. Kinetic simulations underpin this reactivity