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PURPOSE: The accumulation of sphingolipids in Fabry's disease (FD) leads to left ventricular (LV) hypertrophy and shortened T1 in cardiac magnetic resonance (CMR). Early detection of myocardial involvement is essential for the timely initiation and efficacy of enzyme replacement therapy. However, there is a diagnostic gap between the onset of accumulation and detectable myocardial changes. This study aimed to evaluate the diagnostic value of biventricular strain assessment in early FD. METHODS: Genetically proven FD patients (n = 58) and healthy volunteers (HV, n = 62) who had undergone 3 T CMR were retrospectively identified and stratified into 3 groups according to disease severity. Biventricular volumetry, global longitudinal strains (GLS), indexed biventricular masses (RVMi/LVMi), and T1 were evaluated. Group comparisons were performed by ANOVA and diagnostic accuracy was evaluated by ROC-analysis. RESULTS: The study population included 19 group I, 20 group II and 19 group III patients. LV volumetry and T1 showed no significant difference between early FD patients and HV (all p > 0.760). However, RVMi was increased, while RV-GLS and LV-GLS were significantly impaired (p = 0.024 and < 0.001, respectively). Biventricular strains accurately discriminated early FD patients and HV with RV-GLS being non-inferior to LV-GLS (AUC for both 0.83, p > 0.05). Adding strains to the established approach using T1 and LVMi further increased diagnostic accuracy (AUC 0.99, p < 0.05). CONCLUSIONS: Biventricular strains may help detect altered myocardial deformation patterns in phenotypically negative FD patients. These findings may lead to an earlier initiation of therapy, which in turn may slow hypertrophy and the associated long-term risks.

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RATIONALE AND OBJECTIVES: Acute myocarditis (AM) and hypertensive heart disease (HHD) have different pathophysiological backgrounds, thus potentially showing distinct patterns of altered myocardial deformation. Therefore, CMR left ventricular (LV) feature tracking (FT)- based strain parameters were indexed to myocardial mass index (LVMi) in order to evaluate potential additional value in the differentiation among AM, HHD, and healthy volunteers (HV) compared to non-indexed conventional strain. MATERIALS AND METHODS: Patients with AM (n = 43) and HHD (n = 28) underwent CMR at 3T. 61 HV served as controls. Cine imaging-based FT-strain analysis was performed and natural strain (nStrain) values were evaluated for gender and age specific differences in HV. Strain parameters were indexed to LVMi yielding ratio Strain (rStrain). These were evaluated for their discriminatory accuracy compared to nStrain values. RESULTS: There were significant differences in nStrain between genders (p < 0.05), but not between age groups in HV. Circumferential strains differentiated best between HV and AM, reaching an area under the curve (AUC) of 0.86 (female) and 0.81 (male), yielding 93 (72) % sensitivity and 55 (75) % specificity. In discriminating between HV and HHD as well as AM and HHD, longitudinal strains outperformed all other parameters with AUCs of 1.00 (female)/ 0.92 (male) and 0.90 (female)/ 0.74 (male), respectively. Sensitivity and specificity levels of 100 %/ 100 % (female) and 91 %/ 72 % (male) for HV versus AM as well as 82 %/ 71 % (female) and 91%/ 57 % (male) for AM versus HHD could be demonstrated. The usage of rStrains significantly increased the AUC for circumferential and radial strains in male patients. CONCLUSION: rStrain provided additional value in the differentiation of diseases with increased LVM. As rStrain is derived from standard native cine imaging, such parameters can be time efficiently and reliably calculated, giving them the potential to be a powerful addition to the currently developing multiparametric native diagnostic approaches.

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We report the crystal structure of Ba(CN3H4)2 as synthesized from liquid ammonia. Structure solution based on X-ray diffraction data suffers from a severe pseudo-tetragonal problem due to extreme scattering contrast, so the true monoclinic symmetry is detectable only from neutron powder diffraction patterns, and structure solution and refinement was greatly aided by density-functional theory. The symmetry lowering is due to slight deviations of the guanidinate anion from the mirror plane in space group P 4 ‾ b2, a necessity of hydrogen bonding. At 300 K, barium guanidinate crystallizes in P21/c with a=6.26439(2) Å, b=16.58527(5) Å, c=6.25960(2) Å, and a monoclinic angle of ß=90.000(1)°. To improve the data-to-parameter ratio, anisotropic displacement parameters from first-principles theory were incorporated in the neutron refinement. Given the correct structural model, the positional parameters of the heavy atoms were also refinable from X-ray diffraction of a twinned crystal. The two independent guanidinate anions adopt the all-trans- and the anti-shape. The Ba cation is coordinated by eight imino nitrogens in a square antiprism with Ba-N contacts between 2.81 and 3.04 Å. The IR and Raman spectra of barium guanidinate were compared with DFT-calculated phonon spectra to identify the vibrational modes.

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In this Communication, we introduce transmembrane anion transport with pnictogen-bonding compounds and compare their characteristics with chalcogen- and halogen-bonding analogues. Tellurium-centered chalcogen bonds are at least as active as antimony-centered pnictogen bonds, whereas iodine-centered halogen bonds are 3 orders of magnitude less active. Irregular voltage-dependent single-channel currents, high gating charges, and efficient dye leakage support for the formation of bulky, membrane-disruptive supramolecular amphiphiles due to "too strong" binding of anions to tris(perfluorophenyl)stibanes. In contrast, the chalcogen-bonding bis(perfluorophenyl)tellanes do not cause leakage and excel as carriers with nanomolar activity, with P(Cl/Na) = 10.4 for anion/cation selectivity and P(Cl/NO3) = 4.5 for anion selectivity. The selectivities are lower with pnictogen-bonding carriers because their membrane-disturbing 3D structure also affects weaker binders ( P(Cl/Na) = 2.1, P(Cl/NO3) = 2.5). Their 2D structure, directionality, hydrophobicity, and support from proximal anion-π interactions are suggested to contribute to the unique power of chalcogen bonds to transport anions across lipid bilayer membranes.

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Halogen- and chalcogen-based σ-hole interactions have recently received increased interest in non-covalent organocatalysis. However, the closely related pnictogen bonds have been neglected. In this study, we introduce conceptually simple, neutral, and monodentate pnictogen-bonding catalysts. Solution and in silico binding studies, together with high catalytic activity in chloride abstraction reactions, yield compelling evidence for operational pnictogen bonds. The depth of the σ holes is easily varied with different substituents. Comparison with homologous halogen- and chalcogen-bonding catalysts shows an increase in activity from main group VII to V and from row 3 to 5 in the periodic table. Pnictogen bonds from antimony thus emerged as by far the best among the elements covered, a finding that provides most intriguing perspectives for future applications in catalysis and beyond.

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Herein, we introduce catalysts that operate with chalcogen bonds. Compared to conventional hydrogen bonds, chalcogen bonds are similar in strength but more directional and hydrophobic, thus ideal for precision catalysis in apolar solvents. For the transfer hydrogenation of quinolines and imines, rate enhancements well beyond a factor of 1000 are obtained with chalcogen bonds. Better activities with deeper σ holes and wider bite angles, chloride inhibition and correlation with computed anion binding energies are consistent with operational chalcogen bonds. Comparable to classics, such as 2,2'-bipyrroles or 2,2'-bipyridines, dithieno[3,2-b;2',3'-d]thiophenes (DTTs), particularly their diimides, but also wide-angle cyclopentadithiazole-4-ones are identified as privileged motifs to stabilize transition states in the focal point of the σ holes on their two co-facial endocyclic sulfur atoms.

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The benzodiselenazoles (BDS) introduced in this report fulfill, for the first time, all the prerequisites for non-covalent high-precision chalcogen-bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Rational bite-angle adjustment to the long Se-C bonds was the key for BDS design. For the unprecedented BDS motif, synthesis of 12 analogs from o-xylene, crystal structure, σ hole variation strategies, optoelectronic properties, theoretical and experimental anion binding as well as catalytic activity are reported. Chloride binding increases with the depth of the σ holes down to KD = 11 µM in THF. Catalytic activities follow the same trend and culminate in rate enhancements for transfer hydrogenation of quinolines beyond 100 000.

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In this report, we introduce synthetic anion transporters that operate with chalcogen bonds. Electron-deficient dithieno[3,2-b;2',3'-d]thiophenes (DTTs) are identified as ideal to bind anions in the focal point of the σ holes on the cofacial endocyclic sulfur atoms. Anion binding in solution and anion transport across lipid bilayers are found to increase with the depth of the σ holes of the DTT anionophores. These results introduce DTTs and related architectures as a privileged motif to engineer chalcogen bonds into functional systems, complementary in scope to classics such as 2,2'-bipyrroles or 2,2'-bipyridines that operate with hydrogen bonds and lone pairs, respectively.

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To integrate anion-π, cation-π, and ion pair-π interactions in catalysis, the fundamental challenge is to run reactions reliably on aromatic surfaces. Addressing a specific question concerning enolate addition to nitroolefins, this study elaborates on Leonard turns to tackle this problem in a general manner. Increasingly refined turns are constructed to position malonate half thioesters as close as possible on π-acidic surfaces. The resulting preorganization of reactive intermediates is shown to support the disfavored addition to enolate acceptors to an absolutely unexpected extent. This decisive impact on anion-π catalysis increases with the rigidity of the turns. The new, rigidified Leonard turns are most effective with weak anion-π interactions, whereas stronger interactions do not require such ideal substrate positioning to operate well. The stunning simplicity of the motif and its surprisingly strong relevance for function should render the introduced approach generally useful.

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In chemistry and biology, cation-π interactions contribute significantly to many important transformations. In sharp contrast, reactions accomplished with support from the complementary anion-π interactions are essentially unknown. In this report, we show that anion-π interactions can determine the selectivity of the enolate chemistry of malonate half thioesters. Their addition to enolate acceptors is central in natural product biosynthesis but fails without enzymes because non-productive decarboxylation dominates. The newly designed and synthesized anion-π tweezers invert this selectivity by accelerating the disfavored and decelerating the favored process. The discrimination of anionic tautomers of different planarization and charge delocalization on π-acidic surfaces is expected to account for this intriguing "tortoise-and-hare catalysis." Almost exponentially increasing selectivity with increasing π acidity of the catalyst supports that contributions from anion-π interactions are decisive.

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In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated pyridone-derived endoperoxides has led to the development of water-soluble molecules that undergo retro-Diels-Alder reactions in aqueous environment releasing oxygen in high yield and with half-lives of up to 13 h. These molecules in combination with vitamin C as singlet oxygen quencher significantly improved survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygen-depleted conditions.

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