Lifetimes Of Long-lived States Research Articles

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

Long-lived states (LLSs) have lifetimes that can be much longer than longitudinal relaxation times . In molecules containing several geminal pairs of protons in neighboring CH 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 but also the lifetimes 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 (i.e., the slopes of the relaxation rate constants as a function of the radical concentration) are 3 to 5 times smaller than the relaxivities of longitudinal magnetization. Partial delocalization of the LLSs across neighboring CH groups may decrease this advantage, but in practice, this effect was observed to be small, for example, when comparing taurine containing two CH groups and homotaurine with three CH 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.

Research of the Single Crystal and Multilayer Composite Detectors Response Under Irradiation by Fast Neutrons

The object of this work was to study the response of the detectors based on the oxide scintillators under irradiation by a flux of fast neutrons from 239Pu-Be source by counting photomultiplier tube pulses. In the process of the research the counting efficiency of the detectors was measured in units of (pulse×s-1×cm-2)/(neutron×s-1×cm-2) for single-crystal and multilayer composite detectors ZWO (ZnWO4), CWO (CdWO4), BGO (Bi4Ge3O12, composite). The measured response for ZWO detector was ~ 64 pulse/neutron, for CWO ~ 36 pulse/neutron, for BGO ~ 0.44 pulse/neutron. The detectors response was registered by a fast preamplifier with the operation speed of up to 500 MHz, based on high-speed operational amplifiers with voltage feedback. The statistical error of measurement for the neutron registration efficiency by the broadband channel made 7% for the detectors with the effective thickness of ~ 40-50 mm, which is due to the spherical geometry of the experiment. The formation of the detector response is affected by the following parameters of neutron reactions: cross section of inelastic and resonant scattering of scintillator nuclei, density of composite nuclei levels, resonance region width, lifetimes of long-lived states and their number. The measured values of the counting efficiency of fast neutrons registration are accounted for the fact that the inelastic scattering reaction for some nuclei is the starting point that triggers the cascade process of the nuclear states discharge. The registration of the cascade of the discharge gamma-quanta, ranging from nanoseconds to a few microseconds, causes an increase in the detector counting efficiency and, as a consequence, an increase in the detector sensitivity to neutron detection. The observed increase in the counting efficiency of secondary gamma quanta is realized when the neutrons are slowed down in the detectors having sufficiently noticeable thickness and appropriate isotopic composition.

Lifetimes of long-lived states in inhomogeneous magnetic fields

Long-lived states (LLS), also known as singlet states, have been widely studied in the last decade. So far, LLS have only been observed in homogeneous magnetic fields, which preclude applications to many biological samples that are inherently inhomogeneous. We present a method to measure the lifetimes TLLS of long-lived states in inhomogeneous magnetic fields, which combines established sequences for the excitation of LLS with their conversion into long-lived coherences (LLC) that can be detected by windowed acquisition. The method is applied to a pair of diastereotopic scalar-coupled protons of glycine in the dipeptide Alanine-Glycine (Ala-Gly).

Boosting the Sensitivity of Ligand–Protein Screening by NMR of Long-Lived States

A new NMR method for the study of ligand-protein interactions exploits the unusual lifetimes of long-lived states (LLSs). The new method provides better contrast between bound and free ligands and requires a protein-ligand ratio ca. 25 times lower than for established T(1ρ) methods, thus saving on costly proteins. The new LLS method was applied to the screening of inhibitors of urokinase-type plasminogen activator (uPA), which is a prototypical target of cancer research. With only 10 μM protein, a dissociation constant (K(D)) of 180 ± 20 nM was determined for the strong ligand (inhibitor) UK-18, which can be compared with K(D) = 157 ± 39 nM determined by the established surface plasmon resonance method.