Bimodal Fluorescence/Magnetic Resonance Molecular Probes with Extended Spin Lifetimes

Bimodal molecular probes combining nuclear magnetic resonance (NMR) and fluorescence have been widely studied in basic science, as well as clinical research. The investigation of spin phenomena holds promise to broaden the scope of available probes allowing deeper insights into physiological processes. Herein, a class of molecules with a bimodal character with respect to fluorescence and nuclear spin singlet states is introduced. Singlet states are NMR silent but can be probed indirectly. Symmetric, perdeuterated molecules, in which the singlet states can be populated by vanishingly small electron-mediated couplings (below 1 Hz) are reported. The lifetimes of these states are an order of magnitude longer than the longitudinal relaxation times and up to four minutes at 7 T. Moreover, these molecules show either aggregation induced emission (AIE) or aggregation caused quenching (ACQ) with respect to their fluorescence. In the latter case, the existence of excited dimers, which are proposed to use in a switchable manner in combination with the quenching of nuclear spin singlet states, is observe

perfectBASH: Band-selective homonuclear decoupling in peptides and peptidomimetics.

Pure shift techniques have recently attracted much attention, as they have the ability to reduce spectral overlap and thus to simplify the analysis of complex and congested spectral regions. For peptides, band-selective pure shift approaches are often the most reasonable choice among these, when spectra need to be simplified along proton dimensions. Band-selective approaches usually offer the highest sensitivity of all pure shift methods, albeit at the cost that signals can only be acquired in a single-frequency region of the spectrum, in which protons are well isolated in the proton spectrum. For -peptides, signals are usually acquired either in the amide-proton region or in the -proton region. Herein, we present experiments, which enable the pure shift acquisition in both the amide-proton and the -proton regions of -peptides simultaneously, without sacrificing the characteristics of band-selective pure shift methods to provide high sensitivity. The perfectBASH approach discussed here combines the perfect echo experiment with band-selective decoupling. It can be used for band-selective pure shift acquisition of H-1, TOCSY, CLIP-COSY, relayed CLIP-COSY, NOESY, and EASY-ROESY spectra, with proton-proton decoupling over the full backbone region of -peptides, which is most interesting for samples prepared without isotopic enrichment. As the utility of this technique is by no means limited to -peptides, we further illustrate its utility for H-1-NMR studies of a peptidomimetic oligourea

Hyperpolarization of ¹⁵N-pyridinium and ¹⁵N-aniline derivatives by using parahydrogen: New opportunities to store nuclear spin polarization in aqueous media.

Hyperpolarization techniques hold the promise to improve the sensitivity of magnetic resonance imaging (MRI) contrast agents by over 10 000-fold. Among these techniques, para-hydrogen induced polarization (PHIP) allows for generating contrast agents within seconds. Typical hyperpolarized contrast agents are traceable for 2-3 minutes only, thus prolonging tracking-times holds great importance for the development of new ways to diagnose and monitor diseases. Here, we report on the design of perdeuterated 15N-containing molecules with longitudinal relaxation times (T 1) of several minutes. T 1 is a measure for how long hyperpolarization can be stored. In particular, we introduce two new hyperpolarizable families of compounds that we signal enhanced with para-hydrogen: tert-amine aniline derivatives and a quaternary pyridinium compound with 15N-T 1 of about 8 minutes. Especially the latter compound has great potential for applicability since we achieved 15N-polarization up to 8% and the pyridinium motif is contained in a variety of drug molecules and is also used in drug delivery systems

Spontaneous enhancement of magnetic resonance signals using a RASER

Nuclear magnetic resonance is usually drastically limited by its intrinsically low sensitivity: Only a few spins contribute to the overall signal. To overcome this limitation, hyperpolarization methods were developed that increase signals several times beyond the normal/thermally polarized signals. The ideal case would be a universal approach that can signal enhance the complete sample of interest in solution to increase detection sensitivity. Here, we introduce a combination of para-hydrogen enhanced magnetic resonance with the phenomenon of the RASER: Large signals of para-hydrogen enhanced molecules interact with the magnetic resonance coil in a way that the signal is spontaneously converted into an in-phase signal. These molecules directly interact with other compounds via dipolar couplings and enhance their signal. We demonstrate that this is not only possible for solvent molecules but also for an amino acid

Hyperpolarization of amino acids in water utilizing parahydrogen on a rhodium nanocatalyst.

NMR offers many possibilities in chemical analysis, structural investigations, and medical diagnostics. Although it is broadly used, one of NMR spectroscopies main drawbacks is low sensitivity. Hyperpolarization techniques enhance NMR signals by more than four orders of magnitude allowing the design of new contrast agents. Parahydrogen induced polarization that utilizes the para-hydrogen's singlet state to create enhanced signals is of particular interest since it allows to produce molecular imaging agents within seconds. Herein, we present a strategy for signal enhancement of the carbonyl 13 C in amino acids by using parahydrogen, as demonstrated for glycine and alanine. Importantly, the hyperpolarization step is carried out in water and chemically unmodified canonical amino acids are obtained. Our approach thus offers a high degree of biocompatibility, which is crucial for further application. The rapid sample hyperpolarization (within seconds) may enable the continuous production of biologically useful probes, such as metabolic contrast agents or probes for structural biology

“Perfecting” pure shift HSQC: full homodecoupling for accurate and precise determination of heteronuclear couplings

Fully homodecoupled HSQC spectra can be obtained through the use of a new pulse sequence element, "perfectBIRD". By way of illustration, we show that perfectBIRD decoupling allows one-bond residual dipolar couplings (RDCs), which provide important NMR restraints for structure elucidation, to be measured with outstanding precision, even in methylene groups