Bayesian Inference for Model Analyses of Supramolecular Complexes: A Case Study with Nanocarbon Hosts.

A 126 π-electron nanobowl molecule, phenine tridehydrosumanene, was synthesized in 12 steps through the development of a polygon cyclization strategy that assembled the polygonal precursors by Ni-mediated macrocyclization. The bowl-shaped structure accommodated C70 as a guest at the concave site, and the ball-in-bowl structure was determined by X-ray crystallography. The host-guest equilibrium in solution was studied with titration experiments using isothermal calorimetry, which provided an interesting test case for studying the host-guest stoichiometry. Bayesian inference was introduced for stoichiometric analyses of the equilibrium, and a procedure to estimate the volume of prior probability in the parameter space was developed. The Bayesian procedure functioned as Occam's razor and provided quantitative support for a specific stoichiometry. The method was examined with five host-guest examples comprising nanocarbon hosts, which suggested the versatility of Bayesian inference for studies of supramolecular complexes.

Ligand- and metal-exchange reactions of robust nickel complexes with pentagonal bipyramidal structures.

The coordination chemistries of transition metal complexes with pentagonal bipyramidal geometries were investigated, and the highly stable nature of a cyclic pentapyridyl ligand was disclosed. A NiCl2 complex with the pentapyridyl ligand was found to be stable toward water and acidic conditions. The stable complex underwent ligand-exchange reactions with nucleophilic reagents, and a series of pentagonal bipyramidal complexes with different apical ligands was prepared. Crystallographic analyses with the aid of theoretical calculations revealed that the complexes were constructed by electrostatic threading of a divalent linear nickel complex into the ring of the neutral, cyclic pentapyridyl, which resulted in robust water- and acid-resistant complexes with unique pentagonal bipyramidal structures. A reductive metal exchange reaction was then discovered, which enabled "linear divalent metal + electrostatic ring" formulations with different metal atoms.

Stoichiometry validation of supramolecular complexes with a hydrocarbon cage host by van 't Hoff analyses.

Defining chemical processes with equations is the first important step in characterizing equilibria for the assembly of supramolecular complexes, and the stoichiometry of the assembled components must be defined to generate the equation. Recently, this subject has attracted renewed interest, and statistical and/or information-theoretic measures were introduced to examine the validities of the equilibrium models used during curve fitting analyses of titration. The present study shows that these measures may not always be appropriate for credibility examinations and that further reformation of the protocols used to determine the overall stoichiometry is necessary. Hydrocarbon cage hosts and their chloroform complexes formed via weak CH-π hydrogen bonds were studied, which allowed us to introduce van 't Hoff analyses for effective validation of the stoichiometries of supramolecular complexes. This study shows that the stoichiometries of supramolecular complexes should be carefully examined by adopting multiple measures with different origins.

Concise Synthesis of Molecular Hyperboloids by Oligomeric Macrocyclization of Octagonal Molecules.

Molecular hyperboloids were designed and synthesized. The synthesis was achieved by development of oligomeric macrocyclization of an octagonal molecule with a saddle shape. The saddle-shaped molecule, that is, [8]cyclo-meta-phenylene ([8]CMP), was decorated with two linkers for the oligomeric macrocyclization and was synthetically assembled by Ni-mediated Yamamoto coupling. Three congeners of the molecular hyperboloids (2mer-4mer) were obtained, and 2mer and 3mer were subjected to X-ray crystallographic analysis. Crystal structures revealed nanometer-sized hyperboloidal structures with 96π and 144π electrons, which also possessed nanopores on the curved molecular structures. Structures of [8]CMP cores of the molecular hyperboloids were compared with those of saddle-shaped phenine [8]circulene with a negative Gauss curvature to confirm their structural resemblance, which suggests further explorations of expanded networks of molecular hyperboloids.

Akaike's Information Criterion for Stoichiometry Inference of Supramolecular Complexes.

"How do we decide the stoichiometry of host-guest complexes?" This question has long been answered by the Job plot since its first report in 1928. However, as the Job plot was claimed to be misleading in 2016, the question became an open question again and called for renewed investigations. An information-theoretic approach, called Akaike's information criterion, is introduced in this study to select the best model of host-guest complexes, which can rank the models with weight of evidence. A few test cases with unique cylindrical hosts were examined to demonstrate the applicability of the information-theoretic method. Consequently, reasonable views over the thermodynamic behaviors of dumbbell-and-cylinder complexes were obtained. Akaike's information criterion can be a useful and superior alternative to statistical null hypothesis testing, which was proposed as a remedy in place of the Job plot.

Tier-grown Expansion of Design-of-Experiments Parameter Spaces for Synthesis of a Nanometer-scale Macrocycle.

A method to find optimum synthetic conditions was devised by combining a data-driven empirical model with a traditional mechanistic model. In this method, an experimental parameter space was empirically obtained by Design-of-Experiments optimizations with machine-learning supplements and was strategically expanded by examination of the mechanistic model of the reaction paths. An extra tier grown on the original 3×3×3 parameter space succeeded in allocating an optimum reaction condition in the expanded 3×3×4 parameter space. The method was specifically devised for the synthesis of a macrocycle, [n]cyclo-meta-phenylenes ([n]CMP), and the largest congener with n=12 was synthesized and fully characterized for the first time. Crystallographic and photophysical analyses revealed favorable features of [12]CMP for the material applications.

Effect of Left Ventricular Hyperenhancement in Magnetic Resonance Imaging on Reverse Remodeling After Mitral Valve Repair for Moderate Ischemic Mitral Regurgitation.

We aimed to investigate cardiac magnetic resonance imaging (MRI)-derived predictors of a lack of left ventricular (LV) reverse remodeling after undersized mitral annuloplasty (uMAP) for moderate ischemic mitral regurgitation (IMR). We retrospectively reviewed 31 patients who underwent uMAP for moderate IMR and cardiac MRI evaluation between 2004 and 2017. Cardiac MRI evaluation included cine MRI LV and right ventricular volumetric measurements and gadolinium-enhanced MRI assessment of myocardial scarring. LV dimensions were assessed preoperatively, postoperatively, and at follow-up using serial transthoracic echocardiography, and the mid-term (median, 49 months) predictors of a lack of LV reverse remodeling were analyzed. At the mid-term follow-up (mean follow-up period: 85 ± 40 months), 15 patients exhibited reverse LV remodeling. The relative reduction in LV dimension at follow-up was negatively correlated with the preoperative number of LV segments with myocardial infarction (MI) (defined as an LV segment with >25% enhancement). The optimal cut-off for predicting a lack of reverse LV remodeling at follow-up was >5 LV segments with MI, with a sensitivity and specificity of 92% and 92%, respectively. This cut-off value also predicted all-cause mortality at follow-up, with a sensitivity and specificity of 88% and 67%, respectively. The presence of >5 LV segments with MI on gadolinium-enhanced MRI might be a useful predictor of lack of reverse LV remodeling and all-cause mortality outcomes after undersized mitral annuloplasty for moderate IMR.

Phenine design for nanocarbon molecules.

With the name "phenine" given to 1,3,5-trisubstituted benzene for a fundamental trigonal planar unit to weave nanometer-sized networks, a series of curved nanocarbon molecules have been designed and synthesized. Since the 6π-phenine units were amenable to modern biaryl coupling reactions mediated by transition metals, concise syntheses of >400π-nanocarbon molecules were readily achieved. In addition, the phenine design allowed for installing of heteroatoms and/or transition metals doped at specific positions of the large π-systems of the nanocarbon molecules. Fundamental tools were also developed to specify and describe the locations of defects/dopants, quantify pyramidalizations of trigonal panels and estimate molecular Gauss curvatures of the discrete surface. Unique features of phenine nanocarbons, such as stereoisomerism, entropy-driven molecular assembly and effects of dopants on electronic/magnetic characteristics, were revealed during the first half-decade of investigations.

Synthesis of a Negatively Curved Nanocarbon Molecule with an Octagonal Omphalos via Design-of-Experiments Optimizations Supplemented by Machine Learning.

A saddle-shaped nanocarbon molecule was synthesized, which revealed the existence of negative Gauss curvatures on a >3-nm molecular structure possessing 192 π-electrons. The synthesis was facilitated by a protocol developed with Design-of-Experiments optimizations and machine-learning predictions, and spectroscopy and crystallography were used to reveal the saddle-shaped structure of the molecule. Solution-phase analyses showed the presence of dimeric assembly, and crystallographic analyses revealed the stacked dimeric structures. The stacked crystal structure was scrutinized by various methods, including Gauss curvatures derived from the discrete surface theory of geometry, to reveal the important role of the molecular Gauss curvature in dimeric assembly.

Activation of Positive Cooperativity by Size-Mismatch Assembly via Inclination of Guests in a Single-Site Receptor.

A halogenated bowl-shaped guest, corannulene, was encapsulated in a cylindrical host, [4]cyclochrysenylene, to form a bowl-in-tube complex, which mimicked supramolecular complexes between bowl guests and carbon nanotubes. As was the case with carbon nanotubes, the cylindrical space of [4]cyclochrysenylene trapped multiple corannulene molecules in an array, and 1 : 2 complexes were commonly obtained with the corannulene guests with various halogen substituents (F, Cl, Br and I). Careful statistical analyses of isothermal titration calorimetry data succeeded in revealing the stoichiometry, and the molecular structures of the 1 : 2 complexes were further clarified by X-ray crystallographic analyses. Two fluorinated corannulene guests were stacked perpendicular to the cylinder axis, while two chlorinated guests were stacked with inclined orientations. The structural difference resulted in a large difference in the cooperativity of the two-stage association in solution: fluorinated corannulene guests showed negative cooperativity for the 1 : 2 complexation, and the other, larger halogenated corannulene guests showed positive cooperativity.

A minimal cage of a diamond twin with chirality.

A network of tetrahedral vertices can fill three-dimensional (3D) spaces in a beautiful and isotropic manner, which is found as diamonds with sp3-hybridized carbon atoms. Although a network of trigonal vertices (i.e., another form of carbon atoms with sp2-hybridization) naturally results in a lower-dimensional two-dimensional network of graphenes, an isotropic 3D arrangement of trigonal vertices has been of theoretical and mathematical interest, which has materialized as a proposal of a "diamond twin." We herein report the synthesis and optical resolution of a minimal cage of a chiral diamond-twin network. With triangular phenine units at 14 vertices, triply fused decagonal rings were assembled by forming 15 biaryl edges via coupling. A unique chirality of the network has been disclosed with the minimal cage, which may stimulate explorations of chiral carbonaceous materials.

Sufficient cardiac unloading by Impella 5.0 in left ventricular rupture following mitral valve replacement: a case report.

A 72-year-old woman presented with exertional dyspnea. Echocardiography revealed severe mitral valve stenosis; therefore, mitral valve replacement was performed using a bioprosthetic valve. However, left ventricular wall rupture occurred following mitral valve replacement. Under re-cardiac arrest, we found a left ventricular tear under the posterior annulus of the mitral valve. We repaired the left ventricular muscle using a bovine pericardial patch and implanted a bioprosthetic valve again. Postoperatively, we implanted an Impella 5.0 heart pump through the right axillary artery to ensure left ventricular wall unloading. Systemic blood flow depended almost completely on mechanical circulatory assistance until postoperative day 3. After the fourth postoperative day, we started weaning the patient from Impella 5.0. Finally, it was completely discontinued on the sixth postoperative day. After that, the patient's condition was stable, and she was discharged 44 days postoperatively. Impella 5.0 is a potentially beneficial device for left ventricular unloading in patients with left ventricular wall rupture following mitral valve replacement.

A Defective Nanotube Molecule of C552 H496 N24 with Pyridinic and Pyrrolic Nitrogen Atoms.

A 3-nm molecule comprising a cylindrical core and cross-shaped rims was designed and synthesized by developing a modular synthetic route. By using a cyclic precursor from previous studies as a starting material, multiple carbazole units were installed at the rims of the defective cylinder. The defective cylinder was synthetically doped with two types of nitrogen atoms, that is, pyridinic and pyrrolic nitrogen atoms, which resulted in solvatochromic shifts in fluorescence by charge-transfer interactions. The structure of the large, C552 H496 N24 molecule was fully disclosed by crystallographic analyses, and the unique helical arrangement of nitrogen-doped cylinders in the crystal was revealed.

Target-oriented design of helical nanotube molecules for rolled incommensurate bilayers.

Incommensurate double-wall carbon nanotubes give rise to unique stereochemistry originating from twisted stacks of hexagon arrays. However, atomic-level studies on such unique systems have rarely been performed, even though syntheses of molecular segments of carbon nanotubes have been extensively explored. The design of cylindrical molecules with chirality, particularly, in pairs provides synthetic challenges, because relationships between diameters specified with chiral indices and structures of arylene panels have not been investigated in a systematic manner. Here we show that a molecular version of incommensurate double-wall carbon nanotubes can be designed through the development of an atlas for the top-down design of cylindrical molecules. A large-bore cylindrical molecule with a diameter of 1.77 nm was synthesized using a readily available pigment and encapsulated a small-bore cylindrical molecule with a diameter of 1.04 nm. The large- and small-bore molecules possessed helicity in atomic arrangements, and their coaxial assembly proceeded in nonstereoselective manner to give both heterohelical and homohelical combinations.

Metal-Templated Oligomeric Macrocyclization via Coupling for Metal-Doped π-Systems.

A method for the synthesis of metal-doped aromatic macrocycles has been developed. The method, i.e., metal-templated oligomeric macrocyclization via coupling, adopts Ni as the template and assembles five pyridine units via a Ni-mediated coupling reaction to form aryl-aryl linkages. A pentameric oligopyridyl macrocycle was selectively obtained in good yield, and the reaction was also applicable to a gram-scale synthesis. The pentameric oligopyridyl macrocycle captured d8-Ni(II) at the center to form a paramagnetic pentagonal-bipyramidal complex. The method was applied to the synthesis of a large π-molecule to afford a nanometer-sized, bowl-shaped molecule having a unique combination of 120π and 8d electrons.

Raman Spectroscopic Assessment of Myocardial Viability in Langendorff-Perfused Ischemic Rat Hearts.

Spontaneous Raman spectroscopy, which senses changes in cellular contents of reduced cytochrome c, could be a powerful tool for label-free evaluation of ischemic hearts. However, undetermined is whether it is applicable to evaluation of myocardial viability in ischemic hearts. To address this issue, we investigated sequential changes in Raman spectra of the subepicardial myocardium in the Langendorff-perfused rat heart before and during ligation of the left coronary artery and its subsequent release and re-ligation. Under 532-nm wavelength excitation, the Raman peak intensity of reduced cytochrome c at 747 cm-1 increased quickly after the coronary ligation, and reached a quasi-steady state within 30 min. Subsequent reperfusion of the heart after a short-term (30-min) ligation that simulates reversible conditions resulted in quick recovery of the peak intensity to the baseline. Further re-ligation resulted in resurgence of the peak intensity to nearly the identical value to the first ischemia value. In contrast, reperfusion after prolonged (120-min) ligation that assumes irreversible states resulted in incomplete recovery of the peak intensity, and re-ligation resulted in inadequate resurgence. Electron microscopic observations confirmed the spectral findings. Together, the Raman spectroscopic measurement for cytochrome c could be applicable to evaluation of viability of the ischemic myocardium without labeling.

Chemical Reduction of a Nanosized [6]Cyclo-2,7-naphthylene Macrocycle.

Chemical reduction of a naphthylene macrocycle, [6]cyclo-2,7-naphthylene ([6]CNAP, 1), with alkali metals, Li and K, revealed the accessibility of the doubly-reduced state of 1. The macrocyclic 12- anion was isolated in different coordination environments and crystallographically characterized. The single-crystal X-ray diffraction confirmed the formation of contact-ion complexes with one Li+ and two K+ ions in THF, and a "naked" dianion in the solvent-separated ion product with K+ ions in the presence of 18-crown-6 ether. The detailed structural analysis of 12- showed that the π-conjugation over the biaryl linkages between naphthylene panels were enhanced upon two-fold reduction, which was rationally explained by theoretical calculations.

Computational fluid dynamics of internal mammary artery-left anterior descending artery anastomoses.

OBJECTIVES: The aim of this study was to elucidate the remodelling of the internal mammary artery (IMA)-left anterior descending artery anastomosis and compare 2 different anastomosis techniques (end-to-side versus side-to-side) using computational fluid dynamics. METHODS: This study included 9 patients. Computed tomography (CT) angiography was performed immediately after coronary artery bypass grafting (CABG) and at 3-6 months later. The computational fluid dynamics models were made using the CT data. The pulsatile 3-dimensional blood flow was achieved with the finite volume method to evaluate the postoperative morphological and haemodynamic changes at the anastomosis in each patient. Flow velocity distribution, wall shear stress (WSS) and its fluctuation oscillatory shear index were measured. RESULTS: No early or mid-term graft occlusion was observed in the study series. In the side-to-side anastomosis, pouch formation at the distal end of IMA caused a vortex flow with low WSS immediately after CABG. However, at 3-6 months after surgery, this pouch disappeared. As a result, the laminar straight flow with uniform WSS distribution was achieved inside the anastomosis. In the end-to-side anastomosis, the anastomosis shape was remodelled, resulting in a laminar flow pattern with uniform WSS distribution. A patchy high oscillatory shear index was detected at the IMA wall on the top of anastomosis in either anastomosis techniques immediately after the surgery, but it disappeared at 3-6 months after surgery. CONCLUSIONS: Regardless of the anastomosis technique used, a successful remodelling of the IMA-left anterior descending artery anastomosis shape was achieved a few months after surgery, resulting in a straightforward flow streamline, with uniform WSS distribution and minimal oscillatory shear index.

Acyclic, Linear Oligo-meta-phenylenes as Multipotent Base Materials for Highly Efficient Single-layer Organic Light-emitting Devices.

Oligo-meta-phenylenes have been designed and synthesized as multipotent base materials of single-layer organic light-emitting devices. Simple molecular structures of oligo-meta-phenylenes composed of linear phenylene arrays benefited from the wealth of modern reactions available for biaryl couplings and were concisely synthesized in a series. Structure-performance relationship studies with the first seven congeners revealed key features important for the multipotent materials in single-layer devices. As a result, highly efficient phosphorescent electroluminescence was made possible in a highly simplified device architecture comprising one-region, single-layer configurations. Detailed investigations with hole-only devices disclosed that the hole mobility was effectively retarded by potent materials, which should facilitate hole/electron recombination for electroluminescence.

A nitrogen-doped nanotube molecule with atom vacancy defects.

Nitrogen-doped carbon nanotubes have attracted attention in various fields, but lack of congeners with discrete molecular structures has hampered developments based on in-depth, chemical understandings. In this study, a nanotube molecule doped periodically with multiple nitrogen atoms has been synthesized by combining eight 2,4,6-trisubstituted pyridine units with thirty-two 1,3,5-trisubstituted benzene units. A synthetic strategy involving geodesic phenine frameworks is sufficiently versatile to tolerate pyridine units without requiring synthetic detours. Crystallographic analyses adopting aspherical multipole atom models reveal the presence of axially rotated structures as a minor disordered structure, which also provides detailed molecular and electronic structures. The nitrogen atoms on the nanotube serve as chemically distinct sites covered with negatively charged surfaces, and they increase the chance of electron injections by lowering the energy levels of the unoccupied orbitals that should serve as electron acceptors.