A simple supramolecular complex of boronic acid-appended ß-cyclodextrin and a fluorescent boronic acid-based probe with excellent selectivity for d-glucose in water.

Various diboronic acid-based chemosensors for d-glucose have been developed for use in diabetes diagnostic systems. However, most of these chemosensors have limitations, such as poor water solubility, difficulties in synthesis, and inability to selectively detect d-glucose from among other saccharides. We report a simple chemosensor based on a supramolecular complex of fluorophenylboronic acid-appended ß-cyclodextrin (FPB-ßCyD) and an anthracene-based probe having a boronic acid moiety (1). Hydrophobic 1 is encapsulated in the cyclodextrin cavity of FPB-ßCyD, making the supramolecular complex (1/FPB-ßCyD) applicable in a water-rich solvent mixture (98% water). Interestingly, 1/FPB-ßCyD showed a strong turn-on response to d-glucose with a 9.6-fold enhancement in fluorescence intensity, and no response to other saccharides. This study uncovers an innovative approach based on the supramolecular assembly of simple components for the development of a water-soluble d-glucose chemosensor with excellent selectivity.

A Novel AgI -DNA Rod Comprising a One-Dimensional Array of 11 Silver Ions within a Double Helical Structure.

DNA/RNA duplexes containing metal-ion-mediated base pairs (metallo-base pairs) have potential applications in developing nucleic acid-based nanodevices and genetic code expansion. Many metallo-base pairs are formed within duplexes stabilized by Watson-Crick base pairs. Recently, the crystal structure of an AgI -DNA nanowire with an uninterrupted one-dimensional silver array was determined. Here, we present a new DNA helical wire, the "AgI -DNA rod", containing an uninterrupted array of 11 AgI ions. The AgI -DNA rod consisted of only C-AgI -C, G-AgI -G, G-AgI -5-bromouracil (Br U), and Br U-AgI -Br U metallo base pairs, with no Watson-Crick pairs. The AgI -DNA rods were connected by non-canonical G-G pairs in crystals. Notably, data from our absorbance, circular dichroism, nuclear magnetic resonance, and mass spectrometry analyses suggested that the AgI -DNA rods formed in solution, as well as within crystals.

Supramolecular Zn(II)-Dipicolylamine-Azobenzene-Aminocyclodextrin-ATP Complex: Design and ATP Recognition in Water.

Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH2-γ-CyD) for sensing adenosine-5'-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH2-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH2-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH2-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH2-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH2-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH2-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH2-γ-CyD were found to take place for ATP recognition. The "reaction medium approach" enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures.

Effect of Spacer Length in Pyrene-Modified-Phenylboronic Acid Probe/CyD Complexes on Fluorescence-based Recognition of Monosaccharides in Aqueous Solution.

The chemical sensing of saccharides is of importance for the diagnosis of diabetes. Various enzymatic sensors have been developed, but their heat and pH instability issues need to be resolved. In this regard, the development of artificial saccharide sensors with high stability is attracting attention. We have designed a heat- and pH-stable supramolecular inclusion complex system composed of cyclodextrin (CyD) as a host and a phenylboronic acid (PB) probe possessing pyrene as a fluorescent guest. Several probes possessing alkyl spacers having various lengths between the PB and the pyrene moiety, Cn-APB (n = 1 - 4), were newly synthesized and evaluated with respect to their monosaccharide recognition ability on the basis of the fluorescence response through the cyclic esterification of monosaccharide and PB. These Cn-APB/CyD supramolecular inclusion complexes have exhibited a selective fluorescence response towards fructose in aqueous solution based on the photo-induced electron transfer mechanism. The spacer length of the alkyl group in Cn-APB significantly affects the affinity for saccharides. With respect to the complex between C4-APB and PB-modified CyD (3-PB-γ-CyD), it was found that the supramolecular inclusion complexes had high selectivity for glucose with significant fluorescence enhancement. These results indicate that the lengths of the alkyl spacers in the probe molecules are important to control the recognition of saccharides in aqueous solution.

Selective Sugar Recognition by Anthracene-Type Boronic Acid Fluorophore/Cyclodextrin Supramolecular Complex Under Physiological pH Condition.

We synthesized novel PET (photoinduced electron transfer)-type fluorescence glucose probe 1 [(4-(anthracen-2-yl-carbamoyl)-3-fluorophenyl)boronic acid], which has a phenylboronic acid (PBA) moiety as the recognition site and anthracene as the fluorescent part. Although the PBA derivatives dissociate and bind with sugar in the basic condition, our new fluorescent probe can recognize sugars in the physiological pH by introducing an electron-withdrawing fluorine group into the PBA moiety. As a result, the pK a value of this fluorescent probe was lowered and the probe was able to recognize sugars at the physiological pH of 7.4. The sensor was found to produce two types of fluorescent signals, monomer fluorescence and dimer fluorescence, by forming a supramolecular 2:1 complex of 1 with glucose inside a γ-cyclodextrin (γ-CyD) cavity. Selective ratiometric sensing of glucose by the 1/γ-CyD complex was achieved in water at physiological pH.

Structural effects of ditopic azoprobe-cyclodextrin complexes on the selectivity of guest-induced supramolecular chirality.

Benzo-15-crown-5 and dipicolylamine are contained as the binding sites in a ditopic azoprobe (15C5-Azo-n-dpa). However, the selectivities of guest-induced supramolecular chirality for cations and anions were dramatically altered by a slight change in the spacer length of (15C5-Azo-n-dpa)2-γ-CyD complexes in water.

"Frozen Apex" Repair of a Dilated Cardiomyopathy.

We try to make surgical ventricular restoration simpler and more adjustable to safely enhance ventricular function. In eight patients with DiDonato type III dilated cardiomyopathy, we applied a few short-axis purse-string sutures to the endocardial side of the left ventricular apex ("Frozen-Apex" restoration) to make a smaller, cone-shaped apex, based on the concept that the left ventricular apex is important in its existence, but not in its function. The procedure took less than 15 minutes in all the patients. There was no hospital or late death with the follow-up of 549 ± 389 days. Mid-late postoperatively, New York Heart Association functional class changed from 3.5 ± 0.8 (preoperative) to 1.6 ± 0.6 (P = 0.000 vs preoperative), left ventricular diastolic diameter from 64 ± 16 to 61 ± 15 mm, systolic diameter from 57 ± 15 to 50 ± 17mm (P = 0.070), ejection fraction from 27 ± 10 to 40 ± 16% (P = 0.014). Diastolic function as assessed by the ratio of the early to late ventricular filling velocities, the ratio of mitral annular early diastolic velocity to early mitral inflow velocity, and estimated right ventricular pressure remained at the similar level to preoperative one. The new ventricular restoration was associated with better systolic left ventricular function without deteriorating diastolic one. It may improve the outcome of the treatment of selected patients with dilated cardiomyopathy.

Development of Dipicolylamine-Modified Cyclodextrins for the Design of Selective Guest-Responsive Receptors for ATP.

The construction of supramolecular recognition systems based on specific host-guest interactions has been studied in order to design selective chemical sensors. In this study, guest-responsive receptors for ATP have been designed with cyclodextrins (CyDs) as a basic prototype of the turn-on type fluorescent indicator. We synthesized dipicolylamine (DPA)-modified CyD-Cu2+ complexes (Cu·1α, Cu·1ß, and Cu·1γ), and evaluated their recognition capabilities toward phosphoric acid derivatives in water. The UV-Vis absorption and fluorescence spectra revealed that Cu·1ß selectively recognized ATP over other organic and inorganic phosphates, and that ß-CyD had the most suitable cavity size for complexation with ATP. The 1D and 2D NMR analyses suggested that the ATP recognition was based on the host-guest interaction between the adenine moiety of ATP and the CyD cavity, as well as the recognition of phosphoric moieties by the Cu2+-DPA complex site. The specific interactions between the CyD cavity and the nucleobases enabled us to distinguish ATP from other nucleoside triphosphates, such as guanosine triphosphate (GTP), uridine triphosphate (UTP), and cytidine triphosphate (CTP). This study clarified the basic mechanisms of molecular recognition by modified CyDs, and suggested the potential for further application of CyDs in the design of highly selective supramolecular recognition systems for certain molecular targets in water.

Epicardial 15-MHz Echocardiography for Effective Repair of Coronary Arteriovenous Fistula.

In the era of catheter intervention, the surgical repair of coronary arteriovenous fistula needs to be free from residual shunt. Intraoperative epicardial 15-MHz echocardiography helps to find the residual shunt after ligation or obliteration of anomalous vessels. Here we report our method of the echo-assisted surgical repair of coronary arteriovenous fistula in 7 adult patients. The method made the operation for coronary arteriovenous fistula free from residual shunt, but care should be taken to the development of new vessels after the operation.

Development of Supramolecular Saccharide Sensors Based on Cyclodextrin Complexes and Self-assembling Systems.

Cyclodextrins (CDs) are water-soluble host compounds having nano-size hydrophobic cavities that enable them to incorporate organic molecules in water. Optically inert CDs can be efficiently combined with various types of chromoionophores and fluoroionophores. In this study, using diverse combinations of phenylboronic acid fluorescent sensors and azoprobes with CDs, the unique saccharide recognition functions of CD, chemically modified CD, and CD gel complexes based on their synergistic function are clarified, thereby confirming their use as supramolecular saccharide sensors. To realize novel supramolecular chirality, the twisted structure of two ditopic azoprobes inside the γ-CD chiral cavity is controlled by multi-point recognition of guest ions in water. As different types of supramolecular saccharide sensors, phenylboronic acid-based self-assembling systems are also reviewed.

Design and Function of Supramolecular Recognition Systems Based on Guest-Targeting Probe-Modified Cyclodextrin Receptors for ATP.

In this study, we have developed a rational design strategy to obtain highly selective supramolecular recognition systems of cyclodextrins (CyDs) on the basis of the lock and key principle. We designed and synthesized dipicolylamine (dpa)-modified γ-CyD-Cu2+ complexes possessing an azobenzene unit (Cu·1-γ-CyD) and examined how they recognized phosphoric acid derivatives in water. The results revealed that Cu·1-γ-CyD recognized ATP with high selectivity over other phosphoric acid derivatives. The significant blue shift in the UV-vis spectra and 1H NMR analysis suggested that the selective ATP recognition was based on the multipoint interactions between the adenine moiety of ATP and both the CyD cavity and the azobenzene unit in addition to the recognition of phosphoric moieties by the Cu-dpa complex site. Our unique receptor made it capable of distinguishing ATP from AMP and ADP, revealing the discrimination of even a length of one phosphoric group. This study demonstrates that, compared to conventional recognition systems of CyDs, this multipoint recognition system confers a higher degree of selectivity for certain organic molecules, such as ATP, over their similar derivatives.

Guest-induced supramolecular chirality in a ditopic azoprobe-cyclodextrin complex in water.

We report a novel supramolecular chirality induced by the twisted structural change of two ditopic azoprobes (15C5-Azo-dpa) inside the chiral cavity of γ-cyclodextrin (γ-CyD) due to multi-point recognition of guest ions by 15C5-Azo-dpa molecules in water.

Surgical experience with right atrial-aortic fistula and penetration of the superior vena cava by a protruding Accufix atrial J-shaped retention wire.

A 57-year-old woman who had a dual chamber pacemaker implanted in June 1990 for sick sinus syndrome had developed heart failure since 1993. Although fluoroscopy revealed that the proximal J-shaped retention wire of the lead had fractured and had protruded through the outer insulation in 1994, and also that the distal J-shaped retention wire of the lead had protruded through the outer insulation in 1997, a transthoracic echocardiographic examination diagnosed tricuspid valve regurgitation, suggesting that the right atrial-aortic fistula might have been overlooked. In an attempt to avoid migration of the J-shaped retention wire from the lead and to repair the tricuspid regurgitation, it was decided that an operation be performed; however, intraoperative transesophageal echocardiography showed a right atrial-aortic fistula. Intraoperative inspection also revealed that the right atrial-aortic fistula and penetration of the superior vena cava had been caused by the Accufix atrial J-shaped retention wire. Under total cardiopulmonary bypass and induced cardiac arrest, a right atriotomy was performed and the atrial and ventricular leads were removed from the tips. The atrial orifice of the fistula and the aortic orifice were closed. Finally, a new dual-chamber pacing system with bipolar epicardial pacing leads was implanted. Postoperative inspection revealed that the proximal retention wire had fractured, the tip of the retention wire had protruded through the outer insulation, and the distal J-shaped outer insulation was damaged.