Collective long-lived zero-quantum coherences in aliphatic chains.

In nuclear magnetic resonance, long-lived coherences constitute a class of zero-quantum (ZQ) coherences that have lifetimes that can be longer than the relaxation lifetimes T2 of transverse magnetization. So far, such coherences have been observed in systems with two coupled spins with spin quantum numbers I = 1/2, where a term S0T0+T0S0 in the density operator corresponds to a coherent superposition between the singlet S0 and the central triplet T0 state. Here, we report on the excitation and detection of collective long-lived coherences in AA'MM'XX' spin systems in molecules containing a chain of at least three methylene (-CH2-) groups. Several variants of excitation by polychromatic spin-lock induced crossing (poly-SLIC) are introduced that can excite a non-uniform distribution of the amplitudes of terms such as S0S0T0S0S0T0, S0T0S0S0T0S0, and T0S0S0T0S0S0. Once the radio frequency fields are switched off, these are not eigenstates, leading to ZQ precession involving all six protons, a process that can be understood as a propagation of spin order along the chain of CH2 groups before the reconversion into observable magnetization by a second poly-SLIC pulse that can be applied to any one or several of the CH2 groups. In the resulting 2D spectra, the ω2 domain shows SQ spectra with the chemical shifts of the CH2 groups irradiated during the reconversion, while the ω1 dimension shows ZQ signals in absorption mode with linewidths on the order of 0.1 Hz that are not affected by the inhomogeneity of the static magnetic field but can be broadened by chemical exchange as occurs in drug screening. The ZQ frequencies are primarily determined by differences ΔJ between vicinal J-couplings.

Paramagnetic relaxivity of delocalized long-lived states of protons in chains of CH2 groups.

Long-lived states (LLSs) have lifetimes TLLS that can be much longer than longitudinal relaxation times T1. In molecules containing several geminal pairs of protons in neighboring CH2 groups, it has been shown that delocalized LLSs can be excited by converting magnetization into imbalances between the populations of singlet and triplet states of each pair. Since the empirical yield of the conversion and reconversion of observable magnetization into LLSs and back is on the order of 10 % if one uses spin-lock induced crossing (SLIC), it would be desirable to boost the sensitivity by dissolution dynamic nuclear polarization (d-DNP). To enhance the magnetization of nuclear spins by d-DNP, the analytes must be mixed with radicals such as 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL). After dissolution, these radicals lead to an undesirable paramagnetic relaxation enhancement (PRE) which shortens not only the longitudinal relaxation times T1 but also the lifetimes TLLS of LLSs. It is shown in this work that PRE by TEMPOL is less deleterious for LLSs than for longitudinal magnetization for four different molecules: 2,2-dimethyl-2-silapentane-5-sulfonate (DSS), homotaurine, taurine, and acetylcholine. The relaxivities rLLS (i.e., the slopes of the relaxation rate constants RLLS as a function of the radical concentration) are 3 to 5 times smaller than the relaxivities r1 of longitudinal magnetization. Partial delocalization of the LLSs across neighboring CH2 groups may decrease this advantage, but in practice, this effect was observed to be small, for example, when comparing taurine containing two CH2 groups and homotaurine with three CH2 groups. Regardless of whether the LLSs are delocalized or not, it is shown that PRE should not be a major problem for experiments combining d-DNP and LLSs, provided the concentration of paramagnetic species after dissolution does not exceed 1 mM, a condition that is readily fulfilled in typical d-DNP experiments. In bullet d-DNP experiments however, it may be necessary to decrease the concentration of TEMPOL or to add ascorbate for chemical reduction.

Long-lived states of methylene protons in achiral molecules.

In nuclear magnetic resonance (NMR), the lifetimes of long-lived states (LLSs) are exquisitely sensitive to their environment. However, the number of molecules where such states can be excited has hitherto been rather limited. Here, it is shown that LLSs can be readily excited in many common molecules that contain two or more neighboring CH2 groups. Accessing such LLSs does not require any isotopic enrichment, nor does it require any stereogenic centers to lift the chemical equivalence of CH2 protons. LLSs were excited in a variety of metabolites, neurotransmitters, vitamins, amino acids, and other molecules. One can excite LLSs in several different molecules simultaneously. In combination with magnetic resonance imaging, LLSs can reveal a contrast upon noncovalent binding of ligands to macromolecules. This suggests new perspectives to achieve high-throughput parallel drug screening by NMR.

Polychromatic Excitation of Delocalized Long-Lived Proton Spin States in Aliphatic Chains.

Long-lived states (LLS) involving pairs of magnetically inequivalent but chemically equivalent proton spins in aliphatic (CH_{2})_{n} chains can be excited by simultaneous application of weak selective radio frequency fields at n chemical shifts by polychromatic spin-lock induced crossing. The LLS are delocalized throughout the aliphatic chains by mixing of intrapair singlet states and by excitation of LLS comprising products of four and six spin operators. The measured lifetimes T_{LLS} in a model compound are about 5 times longer than T_{1} and are strongly affected by interactions with macromolecules.

Macrocyclic Tetramers-Structural Investigation of Peptide-Peptoid Hybrids.

Outstanding affinity and specificity are the main characteristics of peptides, rendering them interesting compounds for basic and medicinal research. However, their biological applicability is limited due to fast proteolytic degradation. The use of mimetic peptoids overcomes this disadvantage, though they lack stereochemical information at the α-carbon. Hybrids composed of amino acids and peptoid monomers combine the unique properties of both parent classes. Rigidification of the backbone increases the affinity towards various targets. However, only little is known about the spatial structure of such constrained hybrids. The determination of the three-dimensional structure is a key step for the identification of new targets as well as the rational design of bioactive compounds. Herein, we report the synthesis and the structural elucidation of novel tetrameric macrocycles. Measurements were taken in solid and solution states with the help of X-ray scattering and NMR spectroscopy. The investigations made will help to find diverse applications for this new, promising compound class.