Anisotropic Rotational Diffusion Research Articles

Fundamental Limits in Measuring the Anisotropic Rotational Diffusion of Single Molecules.

Many biophysical techniques, such as single-molecule fluorescence correlation spectroscopy, Förster resonance energy transfer, and fluorescence anisotropy, measure the translation and rotation of biomolecules to quantify molecular processes at the nanoscale. These methods often simplify data analysis by assuming isotropic rotational diffusion, e.g., that molecules wobble within a circular cone. This simplification ignores the anisotropy present in many biological contexts that may cause molecules to exhibit different degrees of diffusion in different directions. Here, we loosen this assumption and establish a theoretical framework for describing and measuring anisotropic rotational diffusion using fluorescence imaging. We show that anisotropic wobble is directly quantified by the eigenvalues of a 3-by-3 positive-semidefinite Hermitian matrix M consisting of the second-order moments of a molecule's transition dipole μ. This formalism enables us to model the influence of unavoidable shot noise using a Hermitian perturbation matrix E; the eigenvalues of E directly bound errors in measurements of wobble via Weyl's inequality. Quantifying various perturbations E reveals that anisotropic wobble measurements are generally more sensitive to errors compared to quantifying isotropic wobble. Moreover, severe shot noise can induce negative eigenvalues in estimates of M, thereby causing the anisotropic wobble measurement to fail. Our analysis, using Fisher information, shows that techniques with worse orientation measurement sensitivity experience stronger perturbations E and require larger signal to background ratios to measure anisotropic rotational diffusion accurately. Our work provides deep insights for improving the state of the art in imaging the orientations and anisotropic rotational diffusion of single molecules.

Cross-correlated relaxation in the NMR of near-equivalent spin pairs: Longitudinal relaxation and long-lived singlet order.

The evolution of nuclear spin state populations is investigated for the case of a 13C2-labeled triyne in solution, for which the near-equivalent coupled pairs of 13C nuclei experience cross-correlated relaxation mechanisms. Inversion-recovery experiments reveal different recovery curves for the main peak amplitudes, especially when the conversion of population imbalances to observable coherences is induced by a radio frequency pulse with a small flip angle. Measurements are performed over a range of magnetic fields by using a sample shuttle apparatus. In some cases, the time constant TS for decay of nuclear singlet order is more than 100 times larger than the time constant T1 for the equilibration of longitudinal magnetization. The results are interpreted by a theoretical model incorporating cross-correlated relaxation mechanisms, anisotropic rotational diffusion, and an external random magnetic field. A Lindbladian formalism is used to describe the dissipative dynamics of the spin system in an environment of finite temperature. Good agreement is achieved between theory and experiment.

Orientation dependent proton transverse relaxation in human brain white matter: The magic angle effect on a cylindrical helix

PurposeTo overcome some limitations of previous proton orientation-dependent transverse relaxation formalisms in the human brain white matter (WM) by a generalized magic angle effect function. MethodsA cylindrical helix model was developed embracing anisotropic rotational and translational diffusion of restricted molecules in WM, with the former characterized by an axially symmetric system. Transverse relaxation rates R2 and R2∗ were divided into isotropic R2i and anisotropic parts, R2a ∗ f(α,Φ − ε0), with α denoting an open angle and ε0 an orientation (Φ) offset from DTI-derived primary diffusivity direction. The proposed framework (Fit A) was compared to prior models without ε0 on previously published water and methylene proton transverse relaxation rates from developing, healthy, and pathological WM at 3 T. Goodness of fit was represented by root-mean-square error (RMSE). F-test and linear correlation were used with statistical significance set to P ≤ 0.05. ResultsFit A significantly (P < 0.01) outperformed prior models as demonstrated by reduced RMSEs, e.g., 0.349 vs. 0.724 in myelin water. Fitted ε0 was in good agreement with calculated ε0 from directional diffusivities. Compared with those from healthy adult, the fitted R2i, R2a, and α from neonates were substantially reduced but ε0 increased, consistent with developing myelination. Significant positive (R2i) and negative (α and R2a) correlations were found with aging (demyelination) in elderly. ConclusionThe developed framework can better characterize orientation dependences from a wide range of proton transverse relaxation measurements in the human brain WM, thus shedding new light on myelin microstructural alterations at the molecular level.

Solid-state NMR spectroscopy uncovers internal dynamics of antiviral compounds.

In this study we analyzed the internal dynamics of antiviral compounds such as amantadine and rimantadine and the model compound hexamethylbenzene (HMB) using solid-state 2H NMR spectroscopy. Amantadine and rimantadine have been successfully used to treat influenza and dyskinesia, and their antiviral activity can be characterized using structural and dynamical information from solid-state 2H NMR relaxation. The relaxation data collected for a range of temperatures can be fit using analytical models for the internal dynamics of these compounds to yield physical parameters such as activation energies and diffusion constants that quantify the different modes of motion. Here, we performed quadrupolar-echo and relaxation experiments on powdered samples of deuterated amantadine, rimantadine, and HMB for temperatures between −150⁰C and 60⁰C. HMB displayed two rotational modes about its internal symmetry axes with vastly different timescales. Quadrupolar-echo spectra showed that rimantadine exhibits methyl rotation about its 3-fold axis with no rotation about the C-C axis linked to the cage, while amantadine undergoes slow rotation about the cage axis. The order parameters calculated from the residual quadrupolar couplings for all three compounds were large (>0.8), indicating restricted off-axial dynamics. Spin-lattice (T1Z) and quadrupolar-order relaxation times (T1Q) were calculated for different orientations within the polycrystalline samples. The temperature and angular dependences of these relaxation times were fit using three models: anisotropic rotational diffusion [1,2], axial diffusion, and discrete jumps, among which the anisotropic rotational diffusion model displayed universal applicability. Application of NMR relaxometry to these drugs within the membrane channel will further enable us to understand their activity and the effect of the lipid environment on their structural dynamics.

Cross-correlation effects in the solution NMR spectra of near-equivalent spin-1/2 pairs.

The nuclear magnetic resonance (NMR) spectra of spin-1/2 pairs contain four peaks, with two inner peaks much stronger than the outer peaks in the near-equivalence regime. We have observed that the strong inner peaks have significantly different linewidths when measurements were performed on a 13C2-labelled triyne derivative. This linewidth difference may be attributed to strong cross-correlation effects. We develop the theory of cross-correlated relaxation in the case of near-equivalent homonuclear spin-1/2 pairs, in the case of a molecule exhibiting strongly anisotropic rotational diffusion. Good agreement is found with the experimental NMR lineshapes.

Rotational Dynamics of Nitroxide Biradical in Room-Temperature Ionic Liquids Measured by Quantitative Simulation of EPR Spectra.

Temperature dependences of electron paramagnetic resonance (EPR) spectra of an imidazoline nitroxide biradical spin probe in a series of room-temperature ionic liquids in the temperature range 124-390 K have been quantitatively simulated. The unusual asymmetric EPR spectrum shape previously observed in these systems [Kokorin et al., Appl. Magn. Res. 48 (2016) 287] is shown to originate from anisotropic rotational diffusion of the probe molecule. All experimental spectra were quantitatively reproduced in simulation using a unified set of geometrical and magnetic parameters of the spin probe, which were found to be fully consistent with the biradical geometry obtained from density functional theory calculations. Temperature dependences of rotation diffusion coefficient of the probe characterize the molecular mobility of the ionic liquid, whereas the temperature dependences of the spin-exchange integral J and of the isotropic hyperfine interaction constant, aN, are shown to reflect the intramolecular conformation motions of the biradical probe.

Accurate Prediction of Protein NMR Spin Relaxation by Means of Polarizable Force Fields. Application to Strongly Anisotropic Rotational Diffusion.

Among the various biophysical methods available to investigate protein dynamics, NMR presents the ability to scrutinize protein motions on a broad range of time scales. 1H-15N NMR spin relaxation experiments can reveal the extent of protein motions across the picosecond-nanosecond dynamics probed by the fundamental parameters 15N-R1, 15N-R2, and 1H-15N NOE that can be well sampled by molecular dynamics (MD) simulations. An accurate prediction of these parameters is subjected to a proper description of the rotational diffusion and anisotropy. Indeed, a strong rotational anisotropy has a profound effect on the various relaxation parameters and could be mistaken for conformational exchange. Although the principle of NMR spin relaxation predictions from MD is now well established, numerous NMR/MD comparisons have hitherto focused on proteins that show low to moderate anisotropy and make use of a scaling factor to remove artifacts arising from water model-dependence of the rotational diffusion. In the present work, we have used NMR to characterize the rotational diffusion of the α-helical STAM2-UIM domain by measuring the 15N-R1, 15N-R2, and 1H-15N NOE relaxation parameters. We therefore highlight the use of the polarizable AMOEBA force field (FF) and show that it improves the prediction of the rotational diffusion in the particular case of strong rotational anisotropy, which in turn enhances the prediction of the 15N-R1, 15N-R2, and 1H-15N NOE relaxation parameters without the requirement of a scaling factor. Our findings suggest that the use of polarizable FFs could potentially enrich our understanding of protein dynamics in situations where charge distribution or protein shape is remodeled over time like in the case of multidomain proteins or intrinsically disordered proteins.

Translational and Rotational Diffusion in Liquid Water at Very High Pressure: A Simulation Study.

Translational and rotational diffusion coefficients of liquid water have been computed from molecular dynamics simulation with a recent polarizable potential at 298, 400, and 550 K at very high pressure. At 298 K, the model reproduces the initial increase and the occurrence of a maximum for the translational and rotational diffusion coefficients when the pressure increases. At 400 and 550 K, translational and rotational diffusion coefficients are found to monotonically decrease when pressure increases in the gigapascal range, with the translational coefficient decreasing faster than the rotational one. At 400 K, such an evolution of the rotational diffusion coefficient contrasts with quasielastic neutron scattering results predicting a near independence of the rotational diffusion with a pressure increase above ≃0.5 GPa. An interpretation is proposed to explain this discrepancy. The pressure dependence of the translation-rotation coupling is analyzed. The anisotropy of rotational diffusion is investigated by computing the rotational diffusion tensor in a molecular system of axes and the reorientational correlation times of rank 1 and rank 2 of the inertia axes and of the OH bond vector. Deviation of the simulation data with respect to the predictions of the isotropic Debye model of rotational diffusion are quantified and can be used to estimate experimental rotational diffusion coefficients from experimental reorientational correlation times.

Remarkable Rigidity of the Single α-Helical Domain of Myosin-VI As Revealed by NMR Spectroscopy.

Although the α-helix has long been recognized as an all-important element of secondary structure, it generally requires stabilization by tertiary interactions with other parts of a protein’s structure. Highly charged single α-helical (SAH) domains, consisting of a high percentage (>75%) of Arg, Lys, and Glu residues, are exceptions to this rule but have been difficult to characterize structurally. Our study focuses on the 68-residue medial tail domain of myosin-VI, which is found to contain a highly ordered α-helical structure extending from Glu-6 to Lys-63. High hydrogen exchange protection factors (15–150), small (ca. 4 Hz) 3JHNHα couplings, and a near-perfect fit to an ideal model α-helix for its residual dipolar couplings (RDCs), measured in a filamentous phage medium, support the high regularity of this helix. Remarkably, the hydrogen exchange rates are far more homogeneous than the protection factors derived from them, suggesting that for these transiently broken helices the intrinsic exchange rates derived from the amino acid sequence are not appropriate reference values. 15N relaxation data indicate a very high degree of rotational diffusion anisotropy (D∥/D⊥ ≈ 7.6), consistent with the hydrodynamic behavior predicted for such a long, nearly straight α-helix. Alignment of the helix by a paramagnetic lanthanide ion attached to its N-terminal region shows a decrease in alignment as the distance from the tagging site increases. This decrease yields a precise measure for the persistence length of 224 ± 10 Å at 20 °C, supporting the idea that the role of the SAH helix is to act as an extension of the myosin-VI lever arm.

Toward Multiscale Modeling of Proteins and Bioagglomerates: An Orientation-Sensitive Diffusion Model for the Integration of Molecular Dynamics and the Discrete Element Method.

Most processes involved in biological and biotechnological systems spread over many scales in space and time. For example, the interaction of multiple enzymes in heterogeneous enzymatic agglomerates or clusters, necessary for efficient enzymatic conversion, is of high interest for research and enzyme engineering. In order to understand and predict their overall behavior and performance, it is important to describe these scales as completely as possible, known as multiscale modeling. While many different approaches have been presented in recent years, knowledge about protein formation and bioagglomeration at the micro scale is still very limited. In an attempt to address such systems, we propose a bottom- up multiscale modeling methodology, bridging the gaps between molecular dynamics (MD) with an explicit solvent and the larger scale discrete element method (DEM) using an implicit solvent and abstracting macromolecules (e.g., proteins) as objects with anisotropic properties. We term this approach the molecular discrete element method (MDEM). For this, we present an orientation-sensitive diffusion model for DEM, which describes the dynamics of anisotropic translational and rotational diffusion, while implicitly considering solvent molecules and enforcing a canonical ensemble. A general-purpose model and parametrization approach is presented, which can be used to simulate any process involving diffusion of discrete particles. Effects of temperature and viscosity changes can be considered, and guidance is provided concerning time step selection. This model is generally applicable and serves as a precondition to enforce the proper dynamics (i.e., diffusion characteristics and canonical ensemble, similar to a thermostat in MD) for the proposed multiscale modeling methodology with anisotropic properties. Thereby, it presents a first step toward modeling at the micro scale and is integral to enforcing dynamics of such systems and therefore extensively validated. As a next step, interaction models are to be defined and added to the presented model. In comparison to atomistic and coarse-grained (CG) MD, a speedup of 5-7 orders of magnitude can be achieved. The approach is demonstrated on multiple components of the pyruvate dehydrogenase enzyme complex, a multienzymatic machinery that involves very different types of enzymes and is of high value to further elucidate the mechanisms of bioagglomeration and metabolic channeling.

Nonlinear response theory for Markov processes. III. Stochastic models for dipole reorientations

The nonlinear response of molecular systems undergoing Markovian stochastic reorientations is calculated up to fifth order in the amplitude of the external field. Time-dependent perturbation theory is used to compute the relevant response functions as in earlier treatments (G. Diezemann, Phys. Rev. E{\bf 85}, 051502 (2012), Phys. Rev. E{\bf 96}, 022150 (2017)). Here, we consider the reorientational motion of isolated molecules and extend the existing calculations for the model of isotropic rotational diffusion to the model of anisotropic rotational diffusion and to the model of rotational random jumps. Depending on the values of some model parameters, we observe a hump in the modulus of the nonlinear susceptibility for either of these models. Interestingly, for the model of rotational random jumps, the appearance of this hump depends on the way the coupling to the external field is modelled in the master equation approach. If the model of anisotropic rotational diffusion is considered, the orientation of the diffusion tensor relative to the molecular dipole moment and additionally the amount of anisotropy in the rotational diffusion constants determine the detailed shape of the nonlinear response. In this case, the height of the observed hump is found to increase with increasing 'diffusional anisotropy'. We discuss our results in relation to the features observed experimentally in supercooled liquids.

Fully Anisotropic Rotational Diffusion Tensor from Molecular Dynamics Simulations.

We present a method to calculate the fully anisotropic rotational diffusion tensor from molecular dynamics simulations. Our approach is based on fitting the time-dependent covariance matrix of the quaternions that describe the rigid-body rotational dynamics. Explicit analytical expressions have been derived for the covariances by Favro, which are valid irrespective of the degree of anisotropy. We use these expressions to determine an optimal rotational diffusion tensor from trajectory data. The molecular structures are aligned against a reference by optimal rigid-body superposition. The quaternion covariances can then be obtained directly from the rotation matrices used in the alignment. The rotational diffusion tensor is determined by a fit to the time-dependent quaternion covariances, or directly by Laplace transformation and matrix diagonalization. To quantify uncertainties in the fit, we derive analytical expressions and compare them with the results of Brownian dynamics simulations of anisotropic rotational diffusion. We apply the method to microsecond long trajectories of the Dickerson-Drew B-DNA dodecamer and of horse heart myoglobin. The anisotropic rotational diffusion tensors calculated from simulations agree well with predictions from hydrodynamics.

Spin-label Order Parameter Calibrations for Slow Motion

Calibrations are given to extract orientation order parameters from pseudo-powder electron paramagnetic resonance line shapes of 14N-nitroxide spin labels undergoing slow rotational diffusion. The nitroxide z-axis is assumed parallel to the long molecular axis. Stochastic-Liouville simulations of slow-motion 9.4-GHz spectra for molecular ordering with a Maier–Saupe orientation potential reveal a linear dependence of the splittings, 2A_{hbox{max} } and 2A_{hbox{min} }, of the outer and inner peaks on order parameter S_{zz} that depends on the diffusion coefficient D_{{{text{R}} bot }} which characterizes fluctuations of the long molecular axis. This results in empirical expressions for order parameter and isotropic hyperfine coupling: S_{zz} = s_{1} times left( {A_{hbox{max} } - A_{hbox{min} } } right) - s_{o} and a_{o}^{{}} = tfrac{1}{3}left( {f_{hbox{max} } A_{hbox{max} } + f_{hbox{min} } A_{hbox{min} } } right) + delta a_{o}, respectively. Values of the calibration constants s_{1}, s_{text{o}}, f_{hbox{max} }, f_{hbox{min} } and delta a_{o} are given for different values of D_{{{text{R}} bot }} in fast and slow motional regimes. The calibrations are relatively insensitive to anisotropy of rotational diffusion (D_{{{text{R}}//}} ge D_{{{text{R}} bot }} ), and corrections are less significant for the isotropic hyperfine coupling than for the order parameter.

Anisotropic Rotational Diffusion Studied by Nuclear Spin Relaxation and Molecular Dynamics Simulation: An Undergraduate Physical Chemistry Laboratory

Laboratories studying the anisotropic rotational diffusion of bromobenzene using nuclear spin relaxation and molecular dynamics simulations are described. For many undergraduates, visualizing molecular motion is challenging. Undergraduates rarely encounter laboratories that directly assess molecular motion, and so the concept remains an abstraction. Spin relaxation and molecular dynamics simulations are complementary tools in studying molecular motion in solution. Simulations allow direct visualization of motion. Comparison of simulation results to experimental spin relaxation results enables discussion of the strengths and weaknesses of each technique. Performance of spin relaxation experiments in addition broadens undergraduate perceptions of the utility of NMR spectroscopy. Laboratories which enable the study of the motion of small molecules by both techniques are presented.

ESR study of molecular orientation and dynamics of TEMPO derivatives in CLPOT 1D nanochannels.

The molecular orientations and dynamics of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) radical derivatives with large substituent groups at the 4-position (4-X-TEMPO) in the organic one-dimensional nanochannels within the nanosized molecular template 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) were examined using ESR. The concentrations of guest radicals, including 4-methoxy-TEMPO (MeO-TEMPO) or 4-oxo-TEMPO (TEMPONE), in the CLPOT nanochannels in each inclusion compound (IC) were reduced by co-including 4-substituted-2,2,6,6-tetramethylpiperidine (4-R-TEMP) compounds at a ratio of 1 : 30-1 : 600. At higher temperatures, the guest radicals in each IC underwent anisotropic rotational diffusion in the CLPOT nanochannels. The rotational diffusion activation energy, Ea , associated with MeO-TEMPO or TEMPONE in the CLPOT nanochannels (6-7 kJ mol(-1) ), was independent of the size and type of substituent group and was similar to the Ea values obtained for TEMPO and 4- hydroxy-TEMPO (TEMPOL) in our previous study. However, in the case in which TEMP was used as a guest compound for dilution (spacer), the tilt of the rotational axis to the principal axis system of the g-tensor, and the rotational diffusion correlation time, τR , of each guest radical in the CLPOT nanochannels were different from the case with other 4-R-TEMP. These results indicate the possibility of controlling molecular orientation and dynamics of guest radicals in CLPOT ICs through the appropriate choice of spacer. Copyright © 2016 John Wiley & Sons, Ltd.

High binding yet accelerated guest rotation within a cucurbit[7]uril complex. Toward paramagnetic gyroscopes and rolling nanomachines.

The (15-oxo-3,7,11-triazadispiro[5.1.5.3]hexadec-7-yl)oxidanyl, a bis-spiropiperidinium nitroxide derived from TEMPONE, can be included in cucurbit[7]uril to form a strong (K(a)∼ 2 × 10(5) M(-1)) CB[7]@bPTO complex. EPR and MS spectra, DFT calculations, and unparalleled increased resistance (a factor of ∼10(3)) toward ascorbic acid reduction show evidence of deep inclusion of bPTO inside CB[7]. The unusual shape of the CB[7]@bPTO EPR spectrum can be explained by an anisotropic Brownian rotational diffusion, the global tumbling of the complex being slower than rotation of bPTO around its "long molecular axis" inside CB[7]. The CB[7] (stator) with the encapsulated bPTO (rotator) behaves as a supramolecular paramagnetic rotor with increased rotational speed of the rotator that has great potential for advanced nanoscale machines requiring wheels such as cucurbiturils with virtually no friction between the wheel and the axle for optimum wheel rotation (i.e. nanopulleys and nanocars).

Computer Simulations of Viral Capsid Assembly with Patchy Particle Model

Most viruses use the power of self-assembly to protect and transport their genomic material with the help of a protein capsid. Different computational approaches have been employed to understand the dynamics of the assembly pathway, ranging from molecular dynamics simulations with atomistic detail through Brownian dynamics simulations with coarse-grained interactions to statistical or thermodynamic approaches without any explicit representation of space. We have used coarse-grained Brownian dynamics simulations of a patchy particle model to represent the physically correct assembly dynamics in time and space and at the same time to achieve sufficiently long simulation times to study the statistics of complete capsid self-assembly. In particular, we have developed algorithms that account for the anisotropic translational and rotational diffusion of assembly intermediates and ensure detailed balance for reversible patchy particle models (Klein et al., J. Chem. Phys. 140:184112, 2014). We report on studies of two biologically important questions that can be addressed only in such a computer time-efficient framework: the role of event-driven reactivity in capsid self-assembly (Baschek et al., BMC Biophysics 5:22, 2012) and the role of the rate of capsomere addition (Boettcher et al., preprint 2014). We find that hierarchical assembly is more favorable than direct assembly in the case of stable bonds and that slower capsomere supply is more favorable in order to attain a steady state of continuous capsid assembly.

Holographic measurements of anisotropic three-dimensional diffusion of colloidal clusters

We measure all nonzero elements of the three-dimensional diffusion tensor D for clusters of colloidal spheres to a precision of 1% or better using digital holographic microscopy. We study both dimers and triangular trimers of spheres, for which no analytical calculations of the diffusion tensor exist. We observe anisotropic rotational and translational diffusion arising from the asymmetries of the clusters. In the case of the three-particle triangular cluster, we also detect a small but statistically significant difference in the rotational diffusion about the two in-plane axes. We attribute this difference to weak breaking of threefold rotational symmetry due to a small amount of particle polydispersity. Our experimental measurements agree well with numerical calculations and show how diffusion constants can be measured under conditions relevant to colloidal self-assembly, where theoretical and even numerical prediction is difficult.

Features of Double‐Spiral “Valley‐Hills” Surface Topography Formation in Photochromic Cholesteric Oligomer‐Based Films and Their Changes Under Polarized Light Action

AbstractUsing a novel experimental method combining of polarizing optical microscopy (POM) and atomic force microscopy (AFM), the surface topography and optical properties of chiral‐ photochromic LC systems were studied. For this purpose, a mixture of cholesteric cyclosiloxanes with azobenzene‐containing dopant was prepared. Correlations between the features of surface topography of mixture films and POM images of planarly oriented texture were found. Polarized light action (532 nm) leads to the formation of partially aligned surface structure features. The observed photooptical effects are associated with E‐Z, Z‐E isomerization cycles of azobenzene groups, anisotropic cooperative photoinduced rotational diffusion and directional mass‐transport of chromophores and mesogens in the films.

Molecular Dynamics simulations of liquid isoquinoline as a function of temperature

Molecular Dynamics simulations of isoquinoline in liquid phase have been conducted in the temperature range 300–365K corresponding to the normal liquid phase in order to investigate the evolution of translational and rotational diffusion with temperature. Molecules are supposed to be rigid and interact through an all-atom potential composed of Coulombic and Lennard-Jones terms. Translational diffusion coefficients are computed from velocity autocorrelation functions and mean square displacement. Anisotropic rotational diffusion coefficients are computed from angular velocity autocorrelation functions. The evolution of the 13C spin–lattice relaxation time with temperature has been obtained from the simulations and compared with experimental results. A small non-Arrhenius behavior, more pronounced than what was observed experimentally, has been found for this property. The structure has been analyzed in terms of populations of different kinds of first-neighbor dimers. A continuous evolution of the structure with temperature has been observed. The general trend is thus a continuous smooth evolution of the structure at dimer level and a slight non-Arrhenius evolution for diffusion coefficients and reorientational correlation times. These results are compared with those obtained for liquid quinoline where a clear non-Arrhenius break around 290K was observed for the 13C spin–lattice relaxation time from experiments [D. Jalabert, J.-B. Robert, H. Roux-Buisson, J.-P. Kintzinger, J.-M. Lehn, R. Zinzius, D. Canet, P. Tekely, Europhys. Lett. 15 (1991) 435] and from simulations [C. Millot, J.-C. Soetens, N. Ahmad, R. Adnan, Europhys. Lett. 96 (2011) 43002]. Moreover, the identification of break temperatures for liquid isoquinoline appears to be less clear than for quinoline.