Accessing distributions of exchange and dipolar couplings in stiff molecular rulers with Cu(II) centres.

Determining distributed exchange couplings is important for understanding the properties of synthetic magnetic molecules. Such distributions can be determined from pulsed dipolar spectroscopy (PDS) data, but this is challenging due to the similar influence of both exchange and dipolar couplings on such data. In this work we introduce two models that aim to identify these two contributions to the spin-spin couplings from frequency-domain PDS data of shape-persistent molecules having either two Cu(ii) ions, or a Cu(ii) ion and a nitroxide radical as the paramagnetic moieties. The first model assumes correlated Lorentzian or Gaussian exchange and dipole-dipole coupling distributions whose parameters are the model's unknowns. The second model relies on prior knowledge of the distance distribution and by performing Tikhonov regularization along the exchange coupling dimension yields the latter distribution model-free. Both models were able to differentiate between the absence and the presence of exchange interaction, to determine the coupling regime (ferro- or antiferromagnetic) and to estimate the distribution shape. In contrast, calculations within the exchange resilient model of the neural network analysis implemented in DeerAnalysis2018 were not able for our data to identify exchange couplings and return correct distance distributions. However, the generic model was able to identify and separate the strongly curved intermolecular background in the relaxation-induced dipolar modulation enhancement (RIDME) experiments. Our analysis revealed that in such systems exchange coupling may be present up to at least 3.3 nm in π-conjugated systems involving Cu(ii)-PyMTA, while it is negligible for distances r ≥ 4.5 nm between Cu(ii) ions and r ≥ 3.8 nm between a Cu(ii) ion and an unpaired electron of a nitroxide radical. Disruption of the π-conjugation between the ligand of the Cu(ii) complex and the nitroxide leads to negligible exchange coupling at distances r ≥ 2.6 nm in the corresponding [Cu(ii)-TAHA]-nitroxide ruler. Overall, for cases with known distance distributions, the presented analysis techniques allow to determine distributions of exchange couplings from PDS data.

Gd(III) complexes as paramagnetic tags: Evaluation of the spin delocalization over the nuclei of the ligand.

Complexes of the Gd(III) ion are currently being established as spin labels for distance determination in biomolecules by pulse dipolar spectroscopy. Because Gd(III) is an f ion, one expects electron spin density to be localized on the Gd(III) ion - an important feature for the mentioned application. Most of the complex ligands have nitrogens as Gd(III) coordinating atoms. Therefore, measurement of the (14)N hyperfine coupling gives access to information on the localization of the electron spin on the Gd(III) ion. We carried out W-band, 1D and 2D (14)N and (1)H ENDOR measurements on the Gd(III) complexes Gd-DOTA, Gd-538, Gd-595, and Gd-PyMTA that serve as spin labels for Gd-Gd distance measurements. The obtained (14)N spectra are particularly well resolved, revealing both the hyperfine and nuclear quadrupole splittings, which were assigned using 2D Mims ENDOR experiments. Additionally, the spectral contributions of the two different types of nitrogen atoms of Gd-PyMTA, the aliphatic N atom and the pyridine N atom, were distinguishable. The (14)N hyperfine interaction was found to have a very small isotropic hyperfine component of -0.25 to -0.37MHz. Furthermore, the anisotropic hyperfine interactions with the (14)N nuclei and with the non-exchangeable protons of the ligands are well described by the point-dipole approximation using distances derived from the crystal structures. We therefore conclude that the spin density is fully localized on the Gd(III) ion and that the spin density distribution over the nuclei of the ligands is rightfully ignored when analyzing distance measurements.

Pathological changes in the TMJ and the length of the ramus in patients with confirmed juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is characterized by a progressive destruction of the joints. The temporomandibular joints (TMJ) are especially likely to be affected. The often undetected arthritis in the TMJ in particular can cause significant destruction and craniofacial developmental abnormalities. The aim of this study was to analyze the destructive impact of JIA on TMJ and mandibular development. MATERIAL AND METHODS: We analyzed a total of 92 joints and mandibular rami using digital cone-beam tomography (CBT) and compared 23 consecutively treated JIA patients with 23 healthy controls, matched for age and gender. We evaluated ramus length, vertical depth of the articular fossa, anterior-posterior dimensions of the mandibular head and condylar process. The statistical analysis was performed using non-parametric Wilcoxon and Kruskal-Wallis Rank Sum tests. RESULTS: The JIA patients exhibited significantly more pronounced asymmetries. However, we were unable to detect significant differences in the metric measuring distances. The different JIA subtypes exerted no statistically significant influence. CONCLUSIONS: The possible destruction arising as a result of JIA concerns the TMJ and the length of the mandibular ramus. These craniofacial anomalies demonstrate the central importance of sufficiently early detection and timely treatment in the prevention of such growth disturbances.

Accuracy of endodontic working length determination using cone beam computed tomography.

AIM: To evaluate the accuracy of endodontic working length (WL) measurements by cone beam computed tomography (CBCT). METHODOLOGY: Forty-two extracted human teeth were placed into three full jaw models. Preoperatively, CBCT scans of the models were performed (voxel size: 0.2 mm). Endodontic access cavities were prepared, and the coronal third of 70 root canals were pre-flared. The real WL was measured by inserting a K-file into the root canal until the tip was visible at the foramen, a silicon stopper was adjusted to the corresponding cusp tip, and the length was measured using a micrometer. CBCT WL was simply measured by tracing a line between the apical foramen and the corresponding cusp tip. When the foramen and cusp tip were not visible in one plane, the measurement was taken in two planes. To quantify measurement error, real and CBCT WLs were repeated four times by two experienced operators. Paired analysis for each variable was performed, and the mean of absolute differences and the corresponding 99% confidence intervals were calculated. The t-test was used for comparison. RESULTS: The coefficient of repeatability, reproducibility and interoperator agreement were <0.5 mm. CBCT measurements were accurate; the mean of absolute differences between CBCT and real WL was 0.41 mm (99% CI 0.31-0.52 mm). CONCLUSION: Using a simplified method, CBCT images of 0.2 mm voxel size can be used to accurately determine endodontic WL.

Classification of temporomandibular joint erosion, arthritis, and inflammation in patients with juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis is the most common disease in pediatric rheumatology. It is characterized by chronically progressive joint destruction. The temporomandibular joints (TMJs) are involved in up to 87% of patients and may take an asymptomatic course in 69% of cases. Other than contrast-enhanced magnetic resonance imaging (MRI), there are no reliable screening symptoms or non-invasive procedures available to diagnose the inflammation in its acute form. The goal of this study was to establish an imaging-based classification system for TMJ erosion via MRI and cone-beam computed tomography (CBCT) in an effort to improve indication-specific treatment approaches and to facilitate the comparison of findings. MATERIALS AND METHODS: A total of 46 patients were included. Contrast-enhanced MRI and CBCT images obtained during treatment by pediatric rheumatologists and orthodontists were available from 23 patients with juvenile idiopathic arthritis. We devised a classification system combining the findings of both imaging techniques based on this patient sample in comparison with CBCT findings from an age- and gender-matched group of 23 non-arthritis patients, taking into consideration the available literature and administration of contrast medium. RESULTS: Our cohort of 46 patients comprised 60% female and 40% male patients with a mean age of 14 years, providing a total of 92 TMJs for evaluation. We were able to apply the findings efficiently and conveniently to this classification system with no relevant interobserver differences. Mild structural abnormalities were noted in 21% of TMJs in the control group, whereas 83% of TMJs in the arthritis group exhibited severe anomalies, including cases of extreme destruction. Age and gender did not affect the degree of destruction significantly. CONCLUSION: This is the first classification system to link CBCT and MRI with the use of contrast medium. Contrast-enhanced MRI is an internationally recognized technique that permits acute inflammation to be unequivocally diagnosed. Although structural erosion of the TMJs in our arthritis group was generally severe and significant, we were surprised to observe some cases that were clinically asymptomatic.

Effects of head positioning on cephalometric measurements.

OBJECTIVE: The goal of the present work was to evaluate different head positions for their effects on cephalometric analysis. MATERIALS AND METHODS: Cephalograms were obtained from a skull phantom adjusted to various degrees of inclination (0°, 2°, 4°, 6°, 8°, 10°), lateral tilting (0°, 2°, 4°, 6°, 8°, 10°), and rotation (0°, 3°, 6°, 9°, 12°, 15°, and 21°). All these combinations resulted in a total of 210 digital cephalograms for assessment. On-screen analysis of these images by an orthodontist was completed within a few days. RESULTS: Lateral tilting and rotation revealed considerably stronger effects on the values measured than inclination. Starting at 2° of tilting or 3° of rotation, numerous parameters yielded deviations of ≥ 2° or 2 mm from the baseline values. Increasing degrees of rotation showed more pronounced value changes than increasing degrees of lateral tilting. Skeletal and dental parameters whose landmarks are mainly located in the median plane were less susceptible than parameters whose reference points had to be averaged. Values of parameters located in the median plane were less affected by rotation when combined with higher degrees of initial lateral tilting (> 6°) than with lower ones. CONCLUSION: The usefulness of cephalometric data becomes limited once the head is rotated by 3° or laterally tilted by 2°. Values obtained in the median plane are more stable than those obtained in peripheral locations. Various degrees of inclination applied to the skull phantom with its solid structures had no measurable effects. Accurate head positioning is an essential prerequisite for obtaining meaningful results from cephalograms based on reproducibly identifiable landmarks.

Reference values for three-dimensional surface cephalometry in children aged 3-6 years.

OBJECTIVE: This prospective cross-sectional study design was performed to define reference values for the facial surfaces of 3-6-year-old boys and girls using three-dimensional surface cephalometry. MATERIAL AND METHODS: A total of 2290 standardized three-dimensional facial images from 3 to 6-year-old preschool children were separated by gender and assigned to four age categories. All children were Caucasian and revealed no evidence of dentofacial abnormalities. On each image, 31 cephalometric landmarks were marked, resulting in 35 (19 frontal, six lateral, 10 paired) distances and eight angles. Differences between age groups and genders were calculated and significances detected. RESULTS: A base table with reference values was compiled, which indicated that boys showed higher values than age-matched girls and that measured distances increased with age. CONCLUSION: The mean values from this study could be compiled as a reference table for three-dimensional facial analysis in Caucasian children aged 3-6 years. Such a reference table could be used in comparative studies with other populations or children with craniofacial malformations.

Integration of a maxillary model into facial surface stereophotogrammetry.

AIMS: Three-dimensional (3D) integration of a maxillary model into a facial model has only been possible by a complex procedure using face bow transfer after taking impressions of certain maxillary and facial parts. In this study, we aimed to develop a method for integrating a scanned maxillary model into a scan-realized facial model. MATERIAL AND METHODS: A total of 19 patients with the medical indication for cone-beam computed tomography (CBCT) and orthodontic treatment were included in this study. Facial and maxillary scans were also taken. The construction of the integrated surface model required 10 steps. This integration procedure was evaluated by taking ten 3D dentofacial linear segment measurements in the integrated scan and the CBCT. These results were analyzed using descriptive statistics. RESULTS: All measurements demonstrated good intra-individual reliability. We observed almost perfect congruence between integrated scan and CBCT in vertical distances, while the sagittal measurements revealed more, yet clinically acceptable, deviations possibly caused by different error sources in either of the two methods. CONCLUSION: This new method is suitable for generating 3D integrated surface-scan models which can be used for growth and therapy control studies in orthodontics and other disciplines in the dentofacial fields. Since this method does not require ionizing radiation, it is highly recommendable as an application for children and adolescent patients.

Spin pair geometry revealed by high-field DEER in the presence of conformational distributions.

Orientation selection on two nitroxide-labelled shape-persistent molecules is demonstrated by high-field pulsed electron-electron double resonance experiments at a frequency of 95 GHz with a commercial spectrometer. The experiments are performed with fixed observer and pump frequencies by variation of the magnetic field, so that the variation of both the dipolar frequencies and the modulation depths can be analyzed. By applying the deadtime-free four-pulse double electron-electron resonance (DEER) sequence, the lineshapes of the dipolar spectra are obtained. In the investigated linear biradical and equilateral triradical the nitroxide labels undergo restricted dynamics, so that their relative orientations are not fixed, but are correlated to some extent. In this situation, the general dependence of the dipolar spectra on the observer field can be satisfyingly modelled by simple geometrical models that involve only one rotational degree of freedom for the biradical and two rotational degrees of freedom for the triradical. A somewhat better agreement of the dipolar lineshapes for the biradical is obtained by simulations based on a molecular dynamics trajectory. For the triradical, small but significant deviations of the lineshape are observed with both models, indicating that the technique can reveal deficiencies in modelling of the conformational ensemble of a macromolecule.

Isotope selection in distance measurements between nitroxides.

Self-assembly of spin-labeled synthetic macromolecules or biomacromolecules can lead to structures that contain more than two nitroxide radicals. Label-to-label distance distributions are then poorly resolved since established electron paramagnetic resonance techniques for distance measurements cannot select between the different pairs of nitroxides. A separation into different contributions can be achieved by partially labeling the nitroxide radicals by (15)N or by deuterium and applying pulse electron electron double resonance techniques. With (15)N labeling, strong suppression of either the (14)N or the (15)N contribution can be achieved by suitable choices of the excitation bandwidths and frequencies of the observer subsequence and pump pulse and linear combination of data sets. With deuterium labeling, interactions between only the isotope-labeled nitroxides can be selected by a two-dimensional version of the four-pulse double electron electron resonance experiment. This selection is based on the deep electron spin echo envelope modulation of deuterated nitroxides.

Separation of motional processes in a [2]catenane by combining synthetic, dual-frequency EPR and molecular modelling approaches.

Continuous-wave EPR of nitroxide spin labels at conventional (9.4 GHz) and high (94.2 GHz) frequencies is applied to characterize molecular dynamics in [2]catenanes composed of macrocycles with rigid phenyleneethynylene and flexible alkyl chain building blocks. By using a set of compounds with increasing complexity, which were all labelled at the centre of a rigid building block, it was possible to find regimes where spectral lineshapes were dominated by local motion of the spin label or those that contained information on tumbling of the building blocks. In chloroform, the macrocycles do not move as rigid objects, rather the rigid building block can reorient with some ease, with respect to the rest of the molecule. Furthermore, in that solvent the [2]catenane samples the co-conformational space on a timescale of microseconds or shorter. In a mechanical picture, chloroform can thus be considered as an effective lubricant that prevents the macrocycles from sticking together.

Sensitivity enhancement in pulse EPR distance measurements.

Established pulse EPR approaches to the measurement of small dipole-dipole couplings between electron spins rely on constant-time echo experiments to separate relaxational contributions from dipolar time evolution. This requires a compromise between sensitivity and resolution to be made prior to the measurement, so that optimum data are only obtained if the magnitude of the dipole-dipole coupling is known beforehand to a good approximation. Moreover, the whole dipolar evolution function is measured with relatively low sensitivity. These problems are overcome by a variable-time experiment that achieves suppression of the relaxation contribution by reference deconvolution. Theoretical and experimental results show that this approach leads to significant sensitivity improvements for typical systems and experimental conditions. Further sensitivity improvements or, equivalently, an extension of the accessible distance range can be obtained by matrix deuteration or digital long-pass filtering of the time-domain data. Advantages and limitations of the new variable-time experiment are discussed by comparing it to the established analogous constant-time experiment for measurements of end-to-end distances of 5 and 7.5 nm on rod-like shape-persistent biradicals and for the measurement of a broadly distributed transmembrane distance in a doubly spin-labeled mutant of plant light harvesting complex II.

Ordered nanostructures of a [2]catenane through self-assembly at surfaces--an STM study with sub-molecular resolution.

Model molecular machines can be prepared in solution; their requirements are still more restrictive when anchored onto a surface. Large two-dimensional crystals of [2]catenane were formed on HOPG through self-assembly--the picture shows a 15×15 nm(2) STM image of the surface-bound structure. A comparison with related surface-bound compounds by STM gave insight into the structural requirements for such self-assembly.

Formation, structure and conformational dynamics of highly substituted diphenylcarbonates

The symmetrical carbonates 5-8 were prepared from ethyl 4-hydroxybenzoates with aryl-, 4-(arylethynyl)-phenyl-, arylethynyl- or arylbutadiynyl-substituents in the 3- and 5-positions, by reaction with triphosgene. The choice of base (pyridine, DMAP, NaH) had a strong influence on the conversion: For the synthesis of the carbonates 5 and 6, it was sufficient to use pyridine as the base. However, for the synthesis of the carbonates 7 and 8, NaH had to be used instead. Single-crystal X-ray structure analysis of these carbonates revealed that the substituents point towards the corners of a distorted tetrahedron with the carbonate group sitting in the middle of the tetrahedron and the two angular phenolic building blocks intersecting with an angle of 51-71 degrees. In solution at room temperature, all four substituents are magnetically equivalent as a consequence of conformational flexibility. The two enantiomeric conformers of carbonate 5a interconvert rapidly, probably via a perfect trans conformation with the plane of the Aralpha perpendicular to the carbonate plane. In the case of carbonates 6-8 this process is inhibited by unfavourable interaction of the long substituents at the benzoate moiety. The dynamic process, which has an energy barrier of 8-10 kcalmol(-1), is described in a simplified manner as a continuous rotation of the angular building blocks around the carbonate unit with the C(aryl)-O bonds as the axes of rotation.

EPR probes with well-defined, long distances between two or three unpaired electrons

The synthesis of rod- and star-shaped compounds carrying two or three spin labels as end groups is described. The unpaired electrons are 2.8-5.1 nm apart from each other. The shape-persistent scaffolds were obtained through Pd-Cu-catalyzed alkynyl-aryl coupling and Pd-Cu-catalyzed alkyne dimerization in the presence of oxygen using p-phenyleneethynylene as the basic shape-persistent building block. The spin label 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (4) was attached through esterification of the terminal phenolic OH groups of the scaffold.

Crystalline self-assembly into monolayers of folded oligomers at the air-water interface

Insertion of the 1,3-bis(ethynylene)benzene unit as a rigid spacer into a linear alkyl chain, thus separating the two resulting stems by 9 A. induces chain folding at the air-water interface. These folded molecules self-assemble into crystalline monolayers at this interface, with the plane of the folding unit almost perpendicular to the water surface, as determined by synchrotron grazing-incidence X-ray diffraction. Three distinct molecular shapes, of the types U, inverted U, and M, were obtained in the two-dimensional crystalline state, depending upon the number of spacer units, and the number and position of the hydrophilic groups in the molecule. The molecules form ribbons with a higher crystal coherence in the direction of stacking between the molecular ribbons, and a lower coherence along the ribbon direction. A similar molecule, but with a spacer unit that imposes a 5 A separation between alkyl chains, yields the conventional herringbone arrangement.

Dead-time free measurement of dipole-dipole interactions between electron spins.

A four-pulse version of the pulse double electron-electron resonance (DEER) experiment is presented, which is designed for the determination of interradical distances on a nanoscopic length-scale. With the new pulse sequence electron-electron couplings can be studied without dead-time artifacts, so that even broad distributions of electron-electron distances can be characterized. A version of the experiment that uses a pulse train in the detection period exhibits improved signal-to-noise ratio. Tests on two nitroxide biradicals with known length indicate that the accessible range of distances extends from about 1.5 to 8 nm. The four-pulse DEER spectra of an ionic spin probe in an ionomer exhibit features due to probe molecules situated both on the same and on different ion clusters. The former feature provides information on the cluster size and is inaccessible with previous methods.