Small is Beautiful: Electronic Origin and Synthetic Evolution of Single-Benzene Fluorophores.

ConspectusSingle-benzene fluorophores (SBFs) are small molecules that produce visible light by using only one benzene ring as the sole aromatic core. This Account centers around the chemistry of a new class of SBF that we accidentally discovered but rationally developed and refined afterward. In a failed experiment that took an unintended reaction pathway, we encountered the bright green fluorescence of ortho-diacetylphenylenediamine (o-DAPA). Despite its uninspiring look, reminiscent of textbook examples of simple benzene derivatives, this molecule had neither been synthesized nor isolated before. This discovery led to our studies on the larger DAPA family, including isomeric m-DAPA and p-DAPA. Remarkably, p-DAPA is the lightest red fluorophore, with a molecular weight of only 192. While o- and p-DAPA are emissive, m-DAPA rapidly undergoes internal conversion, facilitated by sequential proton transfer reactions in the excited state.Leveraging the synthetic utility of the amine group, we carried out straightforward single-step modifications to create a full-color SBF library from p-DAPA as the common precursor. During the course of the investigation, we made another fortuitous discovery. With increasing acidity of the N-H group, the excited-state intramolecular proton transfer reaction is promoted, opening up additional pathways for emission to occur at even longer wavelengths. Tipping the balance between the two excited-state tautomers enabled the first example of a single-benzene white-light emitter. We demonstrated the practical utility of these molecules in white light-emitting devices and live cell imaging.According to the particle-in-a-box model, it is difficult to expect a molecule with only one small aromatic ring to produce long-wavelength emission. SBFs rise to this challenge by exploiting electron donor-acceptor pairs around the benzene core, which lowers the energy of light absorption. However, this answers only half of the question. Where do the exceptionally large spectral shifts in the light emission of SBFs originate from? Chemists have long been curious about the molecular mechanisms underlying the dramatic spectral shifts observed in SBFs. Prevailing paradigms invoke the charge transfer (CT) between electron donor and acceptor groups in the excited state. However, without a large π-skeleton for effective charge separation, how could benzene support a CT-type excited state? Our experimental and theoretical studies have revealed that large excited-state antiaromaticity (ESAA) of the benzene core itself is responsible for this remarkable phenomenon. The core matters, not the periphery. With appropriate molecular design, large and extended π-conjugation is no longer a prerequisite for long-wavelength light emission.

Single-Benzene Dual-Emitters Harness Excited-State Antiaromaticity for White Light Generation and Fluorescence Imaging.

Molecular emitters simultaneously generating light at different wavelengths have wide applications. With a small molecule, however, it is challenging to realize two independent radiative pathways. We invented the first examples of dual-emissive single-benzene fluorophores (SBFs). Two emissive tautomers are generated by synthetic modulation of the hydrogen bond acidity, which opens up pathways for excited-state proton transfer. White light is produced by a delicate balance between the energy and intensity of the emission from each tautomer. We show that the excited-state antiaromaticity of the benzene core itself dictates the proton movements driving the tautomer equilibrium. Using this simple benzene platform, a fluorinated SBF was synthesized with a record high solubility in perfluorocarbon solvents. White light-emitting devices and multicolor imaging of perfluorocarbon nanodroplets in live cells demonstrate the practical utility of these molecules.

Variations in Complementary Hydrogen Bonds Direct Assembly Patterns of Isosteric Polyheteroaromatics at Surfaces.

Intermolecular interactions guide self-assembly on the surface. Precise control over these interactions by rational design of the molecule should allow fine control over the self-assembly patterns. Functional groups installed for electronic modulation often induce significant changes in the molecular dimensions, thereby disrupting the original assembly pattern. To overcome this challenge, we have employed a family of isosteric phenazine derivatives, DHP, DAP, and DBQD, to investigate the impacts of hydrogen bonding on two-dimensional molecular self-assembly. While these molecules are similar in size and chemical composition, the strength and directionality of hydrogen bonding differ significantly depending on the chemical structure of donor-acceptor pairs and prototropic tautomerization from positional isomerism. Scanning tunneling microscopy (STM) characterization of the assembled structures on Ag(111), Au(111), and Cu(100) surfaces revealed that minimal changes in molecular structure have a profound impact on the self-assembly patterns. While DHP exhibits highly ordered and robust assemblies, DAP and DBQD show either spatially confined or ill-defined assemblies. In conjunction with hydrogen bonding, prototropic tautomerism is a potent strategy to modulate molecular 2D lattices on surfaces.

Biological Nicotinamide Cofactor as a Redox-Active Motif for Reversible Electrochemical Energy Storage.

Nicotinamide adenine dinucleotide (NAD+ ) is one of the most well-known redox cofactors carrying electrons. Now, it is reported that the intrinsically charged NAD+ motif can serve as an active electrode in electrochemical lithium cells. By anchoring the NAD+ motif by the anion incorporation, redox activity of the NAD+ is successfully implemented in conventional batteries, exhibiting the average voltage of 2.3 V. The operating voltage and capacity are tunable by altering the anchoring anion species without modifying the redox center itself. This work not only demonstrates the redox capability of NAD+ , but also suggests that anchoring the charged molecules with anion incorporation is a viable new approach to exploit various charged biological cofactors in rechargeable battery systems.

The effectiveness of vitamin D3 supplementation in improving functional outcome of non-surgically treated symptomatic lumbar spinal stenosis: Randomized controlled clinical trial - Pilot study.

BACKGROUND: Although vitamin D is one of the essential nutrients associated with musculoskeletal system function, there is no standard treatment method for vitamin D deficiency. This study aimed to investigate the effects of vitamin D supplementation on the improvement in symptoms, functional recovery of the spine, and changes in the quality of life in patients with spinal stenosis. METHODS: In this prospective study, patients with spinal stenosis and serum 25-hydroxy vitamin D levels < 10 ng/mL were randomly assigned to a supplementation group (Group S) and a non-supplementation group (Group NS): 26 participants in Group S (16 females and 10 males) and 25 in Group NS (15 females and 10 males). The degree of lower back pain in both groups was assessed using the visual analog scale; spine function was assessed using the Oswestry disability index and Roland-Morris disability questionnaire; and patient quality of life was assessed using the 36-item short form health survey. We compared and analyzed the values that were measured at baseline, between 4 and 6 weeks (V1), 10 and 12 weeks (V2), and 22 and 26 weeks (V3). RESULTS: No statistically significant difference was observed in lower back pain, spine function, or quality of life between both groups at baseline. In terms of lower back pain in V1, Group S scored 4.15 ±â€…3.12, while Group NS scored 5.64 ±â€…1.85 (P = .045). In V2, Group S scored 3.15 ±â€…2.38, while Group NS scored 4.52 ±â€…1.87 (P = .027). Moreover, in V3, Group S scored 3.58 ±â€…1.65, while Group NS scored 4.60 ±â€…1.68 (P = .033), indicating a statistically significant improvement in each period. CONCLUSION: If a vitamin D deficiency that does not require surgical treatment exists in patients with lumbar spinal stenosis, high-dose vitamin D injections can improve lower back pain, which is the main symptom of lumbar spinal stenosis, as well as the functional outcomes of the spine and quality of life.

Helical fluxionality: numerical frustration drives concerted low-barrier screw motions of a tricopper cluster.

Uneven allocation of resources creates frustration, tension, and conflicts. Confronted with an apparent mismatch between the number of donor atoms and the number of metal atoms to be supported, helically twisted ligands cleverly come up with a sustainable symbiotic solution. As an example, we present a tricopper metallohelicate exhibiting screw motions for intramolecular site exchange. A combination of X-ray crystallographic and solution NMR spectroscopic studies revealed thermo-neutral site exchange of three metal centres hopping back and forth inside the helical cavity lined by a spiral staircase-like arrangement of ligand donor atoms. This hitherto unknown helical fluxionality is a superimposition of translational and rotational movements of molecular actuation, taking the shortest path with an extraordinarily low energy barrier without compromising the overall structural integrity of the metal-ligand assembly.

Prediction of Increased Intracranial Pressure in Traumatic Brain Injury Using Quantitative Electroencephalogram in a Porcine Experimental Model.

Continuous and non-invasive measurement of intracranial pressure (ICP) in traumatic brain injury (TBI) is important to recognize increased ICP (IICP), which can reduce treatment delays. The purpose of this study was to develop an electroencephalogram (EEG)-based prediction model for IICP in a porcine TBI model. Thirty swine were anaesthetized and underwent IICP by inflating a Foley catheter in the intracranial space. Single-channel EEG data were collected every 6 min in 10 mmHg increments in the ICP from baseline to 50 mmHg. We developed EEG-based models to predict the IICP (equal or over 25 mmHg) using four algorithms: logistic regression (LR), naive Bayes (NB), support vector machine (SVM), and random forest (RF). We assessed the performance of each model based on the accuracy, sensitivity, specificity, and AUC values. The accuracy of each prediction model for IICP was 0.773 for SVM, 0.749 for NB, 0.746 for RF, and 0.706 for LR. The AUC of each model was 0.860 for SVM, 0.824 for NB, 0.802 for RF, and 0.748 for LR. We developed a machine learning prediction model for IICP using single-channel EEG signals in a swine TBI experimental model. The SVM model showed good predictive power with the highest AUC value.

Selective oxidative degradation of organic pollutants by singlet oxygen-mediated photosensitization: tin porphyrin versus C60 aminofullerene systems.

This study evaluates the potential application of tin porphyrin- and C(60) aminofullerene-derivatized silica (SnP/silica and aminoC(60)/silica) as (1)O(2) generating systems for photochemical degradation of organic pollutants. Photosensitized (1)O(2) production with SnP/silica, which was faster than with aminoC(60)/silica, effectively oxidized a variety of pharmaceuticals. Significant degradation of pharmaceuticals in the presence of the 400-nm UV cutoff filter corroborated visible light activation of both photosensitizers. Whereas the efficacy of aminoC(60)/silica for (1)O(2) production drastically decreased under irradiation with λ > 550 nm, Q-band absorption caused negligible loss of the photosensitizing activity of SnP/silica in the long wavelength region. Faster destruction of phenolates by SnP/silica and aminoC(60)/silica under alkaline pH conditions further implicated (1)O(2) involvement in the oxidative degradation. Direct charge transfer mediated by SnP, which was inferred from nanosecond laser flash photolysis, induced significant degradation of neutral phenols under high power light irradiation. Self-sensitized destruction caused gradual activity loss of SnP/silica in reuse tests unlike aminoC(60)/silica. The kinetic comparison of SnP/silica and TiO(2) photocatalyst in real wastewater effluents showed that photosensitized singlet oxygenation of pharmaceuticals was still efficiently achieved in the presence of background organic matters, while significant interference was observed for photocatalyzed oxidation involving non-selective OH radical.

Acceptability of the consumer-centric u-health services for patients with chronic obstructive pulmonary disease.

OBJECTIVES: We developed and implemented a system for u-health (ubiquitous healthcare) services for patients with chronic obstructive pulmonary disease (COPD) and studied the level of acceptability by the patients in the context of home visits and telephone education. SUBJECTS AND METHODS: To determine its effectiveness, the u-health service system was used for 2 years with 144 COPD patients in a clinical environment. Patients were provided with the u-healthcare service. RESULTS: Patients with COPD were highly satisfied with the u-healthcare service, which incorporated telemonitoring, teleconsultation, and tele-education along with home visits. The average acceptable fees (in USD) of the service system are as follows: u-health device, $421.28; home visit, $21.53/visit; tele-education, $0.53/min or $26.57/month; and total service fee, $44.26/month. CONCLUSIONS: COPD patients accepted u-health services with a high satisfaction rate, promising a new paradigm of consumer-centric healthcare services.

Effects of consumer-centered u-health service for the knowledge, skill, and attitude of the patients with chronic obstructive pulmonary disease.

Through the use of ubiquitous health, or u-Health, services, medical information can be adapted and made accessible via computer and Internet to provide quality healthcare to anybody, any place, and any time. We developed and implemented u-Health services for patients with chronic obstructive pulmonary disease and studied their experiences with respect to their knowledge of chronic obstructive pulmonary disease and skill and attitude toward the u-Health devices. The u-Health services were composed of telemonitoring and teleconsultation supplemented with home visits. To determine its effectiveness, the u-Health service system was implemented for 2 years with 144 chronic obstructive pulmonary disease patients in a clinical experiment. The subjects were divided into three experimental groups, each provided with different services, compared before and after intervention, and among groups. The analysis of data gathered through the system suggested that u-Health services can support patients with chronic obstructive pulmonary disease, improve patients' knowledge about chronic obstructive pulmonary disease self-management, build u-Health device usage skills, and foster a positive attitude toward u-Health devices. The u-Health services for the chronic obstructive pulmonary disease patients were both feasible and effective from the patients' perspective.

Development of implementation strategies for u-health services based on the healthcare professionals' experiences.

OBJECTIVES: The study develops strategies for implementing ubiquitous healthcare (u-health) based on previous experiences of the healthcare professionals. MATERIALS AND METHODS: Qualitative content analysis, one of qualitative research methods, was used on in-depth interviews conducted between July 21 and October 4, 2009, with 11 healthcare professionals including medical doctors and community healthcare specialist nurses who have previously provided u-health services. RESULTS: Four primary subjects were addressed: (1) subjective experiences on the usability, (2) the expectations, (3) the business prospects, and (4) the prerequisites for the success of u-health market. CONCLUSION: Based on the results of this study, desirable u-health services from the perspective of healthcare professionals were proposed.

Relief of excited-state antiaromaticity enables the smallest red emitter.

It is commonly accepted that a large π-conjugated system is necessary to realize low-energy electronic transitions. Contrary to this prevailing notion, we present a new class of light-emitters utilizing a simple benzene core. Among different isomeric forms of diacetylphenylenediamine (DAPA), o- and p-DAPA are fluorescent, whereas m-DAPA is not. Remarkably, p-DAPA is the lightest (FW = 192) molecule displaying red emission. A systematic modification of the DAPA system allows the construction of a library of emitters covering the entire visible color spectrum. Theoretical analysis shows that their large Stokes shifts originate from the relief of excited-state antiaromaticity, rather than the typically assumed intramolecular charge transfer or proton transfer. A delicate interplay of the excited-state antiaromaticity and hydrogen bonding defines the photophysics of this new class of single benzene fluorophores. The formulated molecular design rules suggest that an extended π-conjugation is no longer a prerequisite for a long-wavelength light emission.

Comparative study of glenoid version and inclination using two-dimensional images from computed tomography and three-dimensional reconstructed bone models.

BACKGROUND: This study was performed to compare glenoid version and inclination measured using two-dimensional (2D) images from computed tomography (CT) scans or three-dimensional (3D) reconstructed bone models. METHODS: Thirty patients who had undergone conventional CT scans were included. Two orthopedic surgeons measured glenoid version and inclination three times on 2D images from CT scans (2D measurement), and two other orthopedic surgeons performed the same measurements using 3D reconstructed bone models (3D measurement). The 3D-reconstructed bone models were acquired and measured with Mimics and 3-Matics (Materialise). RESULTS: Mean glenoid version and inclination in 2D measurements were -1.705º and 9.08º, respectively, while those in 3D measurements were 2.635º and 7.23º. The intra-observer reliability in 2D measurements was 0.605 and 0.698, respectively, while that in 3D measurements was 0.883 and 0.892. The inter-observer reliability in 2D measurements was 0.456 and 0.374, respectively, while that in 3D measurements was 0.853 and 0.845. CONCLUSIONS: The difference between 2D and 3D measurements is not due to differences in image data but to the use of different tools. However, more consistent results were obtained in 3D measurement. Therefore, 3D measurement can be a good alternative for measuring glenoid version and inclination.

Evaluation of left ventricular short- and long-axis function in severe mitral regurgitation using 2-dimensional strain echocardiography.

BACKGROUND: Few data exist on the changes in left ventricular (LV) short- and long-axis function and their usefulness as markers of LV contractile function in patients with chronic, severe mitral regurgitation (MR). METHODS: We studied 59 patients who had severe MR with an ejection fraction > or =50% and 34 healthy controls. Speckle tracking imaging was performed to measure peak systolic radial (SR(R)), circumferential (SR(C)), and longitudinal strain rates (SR(L)). In all patients, the peak rate of LV pressure rise (peak dP/dt) was measured using a micromanometer-tipped catheter. The patients were subdivided into patients with preserved (group 1, peak dP/dt > or =1,300 mm Hg/s [n = 30]) and depressed (group 2 [n = 29]) contractile function. RESULTS: SR(L) was significantly depressed in groups 1 and 2 when compared with the control group, but there was no difference between groups 1 and 2. In contrast, SR(R) and SR(C) were depressed only in group 2, whereas there were no differences between the control group and group 1. SR(R) and SR(C) correlated well with peak dP/dt (r = 0.71, P <.001 and r = -0.63, P <.001, respectively), whereas SR(L) did not. These findings suggest that LV long-axis function becomes depressed earlier than short-axis function in the chronic remodeling process. CONCLUSIONS: Left ventricular short-axis function is a useful marker of LV contractility in patients with chronic, severe MR. Left ventricular long-axis function becomes depressed earlier in the chronic remodeling process. Therefore, evaluation of short-axis as well as long-axis function might be important for better assessment of LV contractile function in these patients.

Overproduction of recombinant human VEGF (vascular endothelial growth factor) in Chinese hamster ovary cells.

Vascular endothelial growth factors (VEGFs) are a family of proteins that mediate angiogenesis. VEGF165 is a VEGF-A isoform and has been extensively studied owing to its potential use in therapeutic angiogenesis. This study established Chinese hamster ovary (CHO) cells overexpressing recombinant human VEGF165 (rhVEGF165) protein. The production rate of the established CHO cells was over 80 mg/l of rhVEGF165 protein from a 7-day batch culture process using a 7.5-l bioreactor with a 5-l working volume and serum-free medium. The rhVEGF165 protein was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure that resulted in a 48% recovery rate. The purified rhVEGF165 protein was a glycosylated homodimeric protein with a higher molecular weight (MW) than the protein expressed from insect cells, suggesting that the glycosylation of the rhVEGF165 protein in CHO cells differed from that in insect cells. The purified rhVEGF165 protein in this study was functionally active with a half-maximal effective concentration of 3.8 ng/ ml and specific activity of 2.5 x 105 U/mg.

The relationship between spontaneous abortion and female workers in the semiconductor industry.

BACKGROUND: This study investigated the relationship between job type and the risk for spontaneous abortion to assess the reproductive toxicity of female workers in the semiconductor industry. METHODS: A questionnaire survey was administered to current female workers of two semiconductor manufacturing plants in Korea. We included female workers who became pregnant at least 6 months after the start of their employment with the company. The pregnancy outcomes of 2,242 female workers who experienced 4,037 pregnancies were investigated. Personnel records were used to assign the subjects to one of three groups: fabrication process workers, packaging process workers, and clerical workers. To adjust for within-person correlations between pregnancies, a generalized estimating equation was used. The logistic regression analysis was limited to the first pregnancy after joining the company to satisfy the assumption of independence among pregnancies. Moreover, we stratified the analysis by time period (pregnancy in the years prior to 2008 vs. after 2009) to reflect differences in occupational exposure based on semiconductor production periods. RESULTS: The risk for spontaneous abortion in female semiconductor workers was not significantly higher for fabrication and packaging process workers than for clerical workers. However, when we stratified by time period, the odds ratio for spontaneous abortion was significantly higher for packaging process workers who became pregnant prior to 2008 when compared with clerical workers (odds ratio: 2.21; 95% confidence interval: 1.01-4.81). CONCLUSIONS: When examining the pregnancies of female semiconductor workers that occurred prior to 2008, packaging process workers showed a significantly higher risk for spontaneous abortions than did clerical workers. The two semiconductor production periods in our study (prior to 2008 vs. after 2009) had different automated processes, chemical exposure levels, and working environments. Thus, the conditions prior to 2008 may have increased the risk for spontaneous abortions in packaging process workers in the semiconductor industry.

Relationship between residential district and health-related quality of life in Chungnam industrial complex area.

OBJECTIVES: This study aimed to evaluate the relationship between residential district of people, such as power plant, steel-mill and petrochemical industries, and health-related quality of life (HRQoL). METHODS: Using a cross-sectional study design, we randomly recruited participants for our study from industrial areas (thermoelectric power plant, steel-mill, petrochemical industry) and rural areas. Logistic regression analysis was used to identify the relationships between Euro quality of life-5 dimension (EQ-5D) scores and living region, while controlling for sociodemographic characteristics. RESULTS: In adjusted model, quality of life decreased with increasing category of age and were lower for females than males. EQ-5D scores of people living in the vicinity of thermoelectric power plant were significant lower than those of people living the vicinity of comparison region (odds ratio, 1.59; 95% confidence interval, 1.00 to 2.53). CONCLUSIONS: Living region of thermoelectric power plant, was strongly associated with scores on the EQ-5D. More research is needed to elucidate the mechanisms which makes the relationship with the living regions and HRQoL.

Evaluation of a simplified augmented reality device for ultrasound-guided vascular access in a vascular phantom.

STUDY OBJECTIVE: To investigate whether a novel ultrasound device may be used with a simplified augmented reality technique, and to compare this device with conventional techniques during vascular access using a vascular phantom. DESIGN: Prospective, randomized study. SETTING: Anesthesiology and Pain Medicine departments of a university-affiliated hospital. PARTICIPANTS: 20 physicians with no experience with ultrasound-guided techniques. MEASUREMENTS: All participants performed the vascular access technique on the vascular phantom model using both a conventional device and the new ultrasound device. Time and the number of redirections of the needle until aspiration of dye into a vessel of the vascular phantom were measured. MAIN RESULTS: The median/interquartile range of time was 39.5/41.7 seconds versus 18.6/10.0 seconds (P < 0.001) and number of redirections was 3/3.5 versus 1/0 (P < 0.001) for the conventional and novel ultrasound devices, respectively. CONCLUSION: During vascular access in a vascular phantom model, the novel device decreased the time and the number of redirections significantly. The device successfully improved the efficiency of the ultrasound-guided vascular access technique.