EPR spectroscopy and molecular dynamics modelling: a combined approach to study liquid crystals

This review outlines the recent theoretical and computational developments for the prediction of motional electron paramagnetic resonance spectra with introduced spin probes from molecular dynamics simulations. The methodology is illustrated with applications to thermotropic and lyotropic liquid crystals at different phases and aggregate states

A combined EPR and MD simulation study of a nitroxyl spin label with restricted internal mobility sensitive to protein dynamics

EPR studies combined with fully atomistic Molecular Dynamics (MD) simulations and an MD-EPR simulation method provide evidence for intrinsic low rotameric mobility of a nitroxyl spin label, Rn, compared to the more widely employed label MTSL (R1). Both experimental and modelling results using two structurally different sites of attachment to Myoglobin show that the EPR spectra of Rn are more sensitive to the local protein environment than that of MTSL. This study reveals the potential of using the Rn spin label as a reporter of protein motions

Enantiopure planar chiral and chiral-at-metal iridacycles derived from bulky cobalt sandwich complexes

Reaction of (η5-(S)-2-(4-methylethyl)oxazolinylcyclopentadienyl)(η4-tetraphenylcyclobutadiene)cobalt with [IrCp*Cl2]2 in acetonitrile with KPF6 and KOt-Bu resulted in S,Sp,SIr and S,Rp,RIr configured acetonitrile and Cp* coordinated cationic iridacycles (d.r. up to 4.8 : 1 – kinetic control), the planar chiral configuration dictating the configuration of the pseudo-tetrahedral iridium-based stereogenic centre. Addition of water to the cycloiridation reaction resulted in an increase in yield (up to 78%) at the cost of diastereoselectivity. Use of the corresponding substrate containing a t-Bu rather than an i-Pr substituted oxazoline gave exclusively the S,Sp,SIr diastereoisomer, and under the same conditions (S)-2-ferrocenyl- 4-(1,1-dimethylethyl)oxazoline cycloiridated to give only the S,Sp,SIr diastereoisomer. Substitution reactions of the title complexes at iridium proceeded with retention of configuration, a computational study revealing the proposed coordinatively unsaturated intermediate of a dissociative mechanism to display a relatively weak Co-Ir interaction, and a pronounced steric effect as the basis of stereocontrol

Rate of molecular transfer of allyl alcohol across an AOT surfactant layer using muon spin spectroscopy

The transfer rate of a probe molecule across the interfacial layer of a water-in-oil (w/o) microemulsion was investigated using a combination of Transverse Field muon spin rotation (TF- μSR), Avoided Level Crossing muon spin resonance (ALC-μSR) and Monte Carlo simulations. Reverse microemulsions consist of nanometer sized water droplets dispersed in an apolar solvent separated by a surfactant monolayer. Although the thermodynamic, static model of these systems has been well described, our understanding of their dynamics is currently incomplete. For example, what is the rate of solute transfer between the aqueous and apolar solvents, and how this is influenced by the structure of the interface? With an appropriate choice of system and probe molecule, µSR offers a unique opportunity to directly probe these interfacial transfer dynamics. Here, we have employed a well characterized w/o microemulsion stabilized by bis(2-ethylhexyl) sodium sulphosuccinate (Aerosol OT), with allyl alcohol (CH2=CH-CH2-OH, AA) as the probe. Resonances due to both muoniated radicals, CMuH2-C*H-CH2-OH and C*H2-CHMu-CH2-OH, were observed with the former being the dominant species. All resonances displayed solvent dependence, with those in the microemulsion observed as a single resonance located at intermediate magnetic fields to those present in either of the pure solvents. Observation of a single resonance is strong evidence for interfacial transfer being in the fast exchange limit. Monte-Carlo calculations of the ΔM=0 ALC resonances are consistent with the experimental data, indicating exchange rates greater than 109 s-1, placing the rate of interfacial transfer at the diffusion limit

Baseline electroencephalogram and its evolution after activation of dopaminergic system by apomorphine in middle-aged 5xfad transgenic mice, a model of alzheimer’s disease

Aging and Alzheimer’s disease (AD) are characterized by common pathological features associated with alterations in neuronal connections. These inevitably affect the functioning of specific brain areas and their interrelations, leading to questions about neuronal plasticity and the compensatory mechanisms associated with dopaminergic (DA) mediation. In this study on twelve-month-old freely moving 5XFAD-transgenic mice, serving as a model of AD, and their wild-type (WT) littermates, we analyze electroencephalograms (EEGs) from the motor cortex (MC), putamen (Pt) and the DA-producing ventral tegmental area (VTA) and substantia nigra (SN). Baseline EEGs in the transgenic mice were characterized by delta 2 activity enhancements in VTA and alpha attenuation in VTA and SN. In contrast to WT mice, which lack differences in EEG from these brain areas, 5XFAD mice showed theta–alpha attenuation and delta 2 and beta 2 enhancements in EEG from both VTA and SN vs. MC. In 5XFAD mice, a DA mimetic, apomorphine, lowered (vs. saline) the theta oscillations in Pt, VTA and SN and enhanced alpha in MC, Pt, VTA and beta 1 in all brain areas. These results and those obtained earlier in younger (six-month-old) mice suggest that the age-related characteristics of cerebral adaptive mechanisms affected by AD might be associated with modification of dopaminergic mediation in the mechanisms of intracerebral dynamic interrelations between different brain areas

EPR detection and characterisation of a paramagnetic Mo(III) dihydride intermediate involved in electrocatalytic hydrogen evolution

EPR spectroscopy and theoretical data show that the slow heterogeneous electron-transfer kinetics associated with the reduction of an 18-electron Mo(IV) acetato dihydride are a consequence of an η2−η1 rearrangement of the carboxylate ligand which gives a unique paramagnetic 17-electron Mo(III) dihydride

DEER and RIDME Measurements of the Nitroxide-Spin Labelled Copper-Bound Amine Oxidase Homodimer from Arthrobacter Globiformis

In the study of biological structures, pulse dipolar spectroscopy (PDS) is used to elucidate spin–spin distances at nanometre-scale by measuring dipole–dipole interactions between paramagnetic centres. The PDS methods of Double Electron Electron Resonance (DEER) and Relaxation Induced Dipolar Modulation Enhancement (RIDME) are employed, and their results compared, for the measurement of the dipolar coupling between nitroxide spin labels and copper-II (Cu(II)) paramagnetic centres within the copper amine oxidase from Arthrobacter globiformis (AGAO). The distance distribution results obtained indicate that two distinct distances can be measured, with the longer of these at c.a. 5 nm. Conditions for optimising the RIDME experiment such that it may outperform DEER for these long distances are discussed. Modelling methods are used to show that the distances obtained after data analysis are consistent with the structure of AGAO

Molecular electrometer and binding of cations to phospholipid bilayers

Despite the vast amount of experimental and theoretical studies on the binding affinity of cations -especially the biologically relevant Na+ and Ca2+ - for phospholipid bilayers, there is no consensus in the literature. Here we show that by interpreting changes in the choline headgroup order parameters according to the 'molecular electrometer' concept [Seelig et al., Biochemistry, 1987, 26, 7535], one can directly compare the ion binding affinities between simulations and experiments. Our findings strongly support the view that in contrast to Ca2+ and other multivalent ions, Na+ and other monovalent ions (except Li+) do not specifically bind to phosphatidylcholine lipid bilayers at sub-molar concentrations. However, the Na+ binding affinity was overestimated by several molecular dynamics simulation models, resulting in artificially positively charged bilayers and exaggerated structural effects in the lipid headgroups. While qualitatively correct headgroup order parameter response was observed with Ca2+ binding in all the tested models, no model had sufficient quantitative accuracy to interpret the Ca2+: lipid stoichiometry or the induced atomistic resolution structural changes. All scientific contributions to this open collaboration work were made publicly, using nmrlipids. blogspot.fi as the main communication platform.Peer reviewe