Showing papers by "Seth M. Cohen published in 2010"

Moisture-Resistant and Superhydrophobic Metal−Organic Frameworks Obtained via Postsynthetic Modification

Abstract: Postsynthetic covalent modification of metal−organic frameworks (MOFs) with long alkyl substituents is shown to protect these materials against moisture. These MOFs, which normally display hydrophilic properties, are readily converted into hydrophobic or superhydrophobic materials. Overcoming the inherent sensitivity of MOFs to water represents a major step forward in their widespread use in technology applications.

Modifying MOFs: new chemistry, new materials

Abstract: The postsynthetic modification (PSM) of metal–organic frameworks (MOFs) has grown substantially in the past few years. In this minireview, recent progress in the area of PSM is highlighted, with an emphasis on several recent advancements. The scope and limitations of PSM are described and future prospects are discussed.

Self-Reported Impact of Dysphonia in a Primary Care Population: An Epidemiological Study

Abstract: Objectives/Hypothesis: This study's objectives are to 1) to assess the prevalence of dysphonia in the primary care community, 2) evaluate the severity of dysphonia, 3) explore potential risk factors for dysphonia, 4) examine the treatment of dysphonic patients, and 5) assess treatment-related barriers. The hypotheses are that 1) dysphonia is common in the primary care community, 2) it adversely impacts patients' quality of life (QOL), and 3) patients are underevaluated and experience obstacles with respect to seeking treatment. Study Design: Cross-sectional, practice-based study in the primary care population. Methods: English-speaking patients 18 years of age and older were recruited from a primary care research network. Patients presenting to their primary care practices were given a packet of questionnaires to complete that documented demographic information, risk factors, presence of dysphonia, prior treatment, and reasons for not seeking treatment. The Voice-Related Quality of Life (VRQOL) and Center for Epidemiological Studies-Depression Scale (CES-D) served as quality-of-life outcome measures. A priori sample size calculations were performed indicating a sample size of 780. Univariate analyses, descriptive statistics, odds ratios and 95% confidence intervals, and multivariate analyses were performed. Results: A total of 789 patients with a mean age of 49.9 years and range of 18 to 94 years participated. Lifetime prevalence of dysphonia was 29.1%, point prevalence of dysphonia 7.5%, and 4.3% had had dysphonia for >4 weeks. Of those with current dysphonia, only 46% had not missed work. Of those with current dysphonia, 73.3% had had dysphonia more than once. Patients with dysphonia had lower VRQOL scores and higher CES-D scores (t test, P ≤.001). Risk factors for dysphonia and impaired VRQOL on multivariate analysis included neurologic disease, dry mouth, family history of dysphonia, college or postgraduate level education, allergies or sinus problems, neck pain, medication for depression/anxiety, more than three upper respiratory infections per year, gastroesophageal reflux at least monthly, and asthma or lung disease. Of the patients who had ever had dysphonia, 22.1% received treatment. Common treatment modalities included antireflux treatment, antiallergy treatment, and antibiotics. Speech-language pathology evaluation was rare. Compared to those not interested in treatment, patients wanting treatment were more likely to have chronic dysphonia >4 weeks (30.6% vs. 8.1%; χ2, P ≤.001), more likely to have dysphonia more than once (85.1% vs. 58.0%; χ2, P ≤.001), and lower VRQOL scores (median 67.5 vs. 97.5; rank sum test, P <.001). Reasons for not seeking treatment included thinking the dysphonia would go away, physicians did not ask about voice problems, and being unaware of treatment options. Conclusions: At the time one in 13 primary care patients had dysphonia resulting in significant functional impairment with reduced voice-specific QOL and greater depression scores. Risk factors for dysphonia and voice-specific QOL impairment were identified and might be useful for identifying patients at risk for dysphonia. Barriers exist that prevent dysphonic patients from receiving evaluation and treatment. Whether improved methods of dysphonia screening leads to better outcomes and reduced societal impact needs investigation. Laryngoscope, 2010

Tuning hydrogen sorption properties of metal-organic frameworks by postsynthetic covalent modification.

Abstract: Postsynthetic modification is presented as a means to tune the hydrogen adsorption properties of a series of metal-organic frameworks (MOFs). IRMOF-3 (isoreticular metal-organic framework), UMCM-1-NH(2) (University of Michigan crystalline material), and DMOF-1-NH(2) (DABCO metal-organic framework) have been covalently modified with a series of anhydrides or isocyanates and the hydrogen sorption properties have been studied. Both the storage capacities and isosteric heats of adsorption clearly show that covalent postsynthetic modification can significantly enhance the sorption affinity of MOFs with hydrogen and in some cases increase both gravimetric and volumetric uptake of the gas as much as 40 %. The significance of the present study is illustrated by: 1) the nature of the substituents introduced by postsynthetic modification result in different effects on the binding of hydrogen; 2) the covalent postsynthetic modification approach allows for systematic modulation of hydrogen sorption properties; and 3) the ease of postsynthetic modification of MOFs allows a direct evaluation of the interplay between MOF structure, hydrogen uptake, and heat of adsorption. The findings presented herein show that postsynthetic modification is a powerful method to manipulate and better understand the gas sorption properties of MOFs.

Hydrogen Peroxide Activated Matrix Metalloproteinase Inhibitors: A Prodrug Approach

Abstract: Matrix metalloproteinases (MMPs) are a family of structurally related ZnII-dependent hydrolytic enzymes involved in the breakdown of the extracellular matrix.[1] MMPs are secreted as zymogens, and are activated by cleavage of the propeptide domain by proteases, other MMPs, or by reactive oxygen species (ROS). In particular, the activation of MMPs by ROS during ischemia-induced inflammatory response leads to the breakdown of the blood–brain barrier (BBB) resulting in edema and cell death.[2,3] The strong correlation between ROS-activation of MMPs and the disruption of the BBB has led to several studies on the use of MMP inhibitors (MMPi) as therapeutics for treating reperfusion injury associated with stroke.[4] Inhibition of MMPs after stroke with a variety of broad-spectrum MMPi have shown that MMP inhibition greatly reduced ischemic brain injury.[5,6] While the use of MMPi to reduce the effects of BBB disruption following stroke has been clearly established, the major challenge for MMPi in this area is the need for temporal and spatial control of their inhibitory activity.[7]

Evaluation of Heterogeneous Metal−Organic Framework Organocatalysts Prepared by Postsynthetic Modification

Abstract: A metal−organic framework (MOF) containing 2-amino-1,4-benzenedicarboxylate (NH2−BDC) as a building block is shown to undergo chemical modification with a set of cyclic anhydrides. The modification of the aluminum-based MOF known as MIL-53(Al)-NH2 (MIL = Material Institut Lavoisier) by these reagents is demonstrated by using a variety of methods, including NMR and electrospray ionization mass spectrometry (ESI-MS), and the structural integrity of the modified MOFs has been confirmed by thermal gravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Reaction with these cyclic anhydrides produces MOFs that display carboxylic acid functional groups within their pores. Furthermore, it is shown that maleic acid functionalized MIL-53(Al)-AMMal can act as a Bronsted acid catalyst and facilitate the methanolysis of several small epoxides. Experiments show that MIL-53(Al)-AMMal acts in a heterogeneous manner and is recyclable with consistent activity over at least three catalytic cycles. The findings prese...

Generating Reactive MILs: Isocyanate‐ and Isothiocyanate‐Bearing MILs through Postsynthetic Modification

Abstract: Metal–organic frameworks (MOFs) are rapidly becoming one of the most widely studied porous materials. 2] This family of hybrid compounds, constructed from inorganic and organic components, exhibit a diverse range of architectures with unprecedented porosity and show promise in applications including gas, liquid and vapor storage, separations, drug delivery, and catalysis. 4] Among the many MOFs synthesized, aluminum-based MOFs, developed largely by the group of F rey under the name Material Institut Lavoisier (MIL), exhibit particularly attractive features including high-surface areas, thermal stability, and chemical stability. An increasingly recognizable advantage of MOF materials, over conventional inorganic porous solids (e.g. zeolites), is the ability to integrate complex chemical functionalities, under mild conditions, onto the organic constituents of the lattice. This strategy, often referred to as postsynthetic modification (PSM), can provide access to porous materials with enhanced properties for specialized applications, such as gas sorption, catalysis, and biomedical uses. PSM is generally achieved by using a pre-installed moiety on the precursor ligand that can be coupled with a reactive species in a heterogeneous fashion. Despite much progress in this area, the generation of a highly reactive chemical species as part of the organic strut of the MOF lattice has not been reported to date. Herein, we show that the superior chemical stability of MILs allows for the synthesis of reactive isocyanate and isothiocyanate groups on the organic components of the framework. Under suitable conditions, these reactive groups readily combine with species diffusing through the porous structure, generating new functionalized MILs (Figure 1). To the best of our knowledge, this report is the

From Sensors to Silencers: Quinoline- and Benzimidazole-Sulfonamides as Inhibitors for Zinc Proteases

Abstract: Derived from the extensive work in the area of small molecule zinc(II) ion sensors, chelating fragment libraries of quinoline- and benzimidazole-sulfonamides have been prepared and screened against several different zinc(II)-dependent matrix metalloproteinases (MMPs). The fragments show impressive inhibition of these metalloenzymes and preferences for different MMPs based on the nature of the chelating group. The findings show that focused chelator libraries are a powerful strategy for the discovery of lead fragments for metalloprotein inhibition.

Search for a Lorentz-violating sidereal signal with atmospheric neutrinos in IceCube

Abstract: A search for sidereal modulation in the flux of atmospheric muon neutrinos in IceCube was performed. Such a signal could be an indication of Lorentz-violating physics. Neutrino oscillation models, derivable from extensions to the standard model, allow for neutrino oscillations that depend on the neutrino's direction of propagation. No such direction-dependent variation was found. A discrete Fourier transform method was used to constrain the Lorentz and CPT-violating coefficients in one of these models. Because of the unique high energy reach of IceCube, it was possible to improve constraints on certain Lorentz-violating oscillations by 3 orders of magnitude with respect to limits set by other experiments.

Postsynthetic diazeniumdiolate formation and NO release from MOFs

Abstract: Two different metal–organic frameworks (MOFs) have been modified with nitric oxide (NO) through covalent postsynthetic modification (PSM) to form diazeniumdiolate-functionalized and releasing MOFs.

Modular, active, and robust Lewis acid catalysts supported on a metal-organic framework.

Abstract: Metal−organic frameworks (MOFs) have shown promise as heterogeneous catalysts because of their high crystallinity, uniform pores, and ability to be chemically and physically tuned for specific chemical transformations. One of the challenges with MOF-based catalysis is few systems achieve all of the desired features for a heterogeneous catalyst, including high activity, robustness (recyclability), and excellent selectivity. Herein, postsynthetic modification (PSM) of a MOF is used to synthesize a series of MOF catalysts that are highly robust and active for epoxide ring-opening reactions. In the following study, four metalated MOFs (UMCM-1-AMInpz, UMCM-1-AMInsal, UMCM-1-AMFesal, and UMCM-1-AMCupz) are examined as catalysts for β-azido and β-amino alcohol synthesis with epoxides of varying sizes and shapes using two different nucleophiles (TMSN3 and aniline). The four MOFs are isostructural, exhibit good thermal and structural stability, and display different catalytic activities based on the combination of...

Chelator fragment libraries for targeting metalloproteinases

Abstract: A chelator fragment library based on a variety of metal binding groups was screened against a metalloproteinase. Lead hits were identified and an expanded library of select compounds was synthesized, resulting in numerous high-affinity hits against several metalloprotein targets. The findings clearly demonstrate that chelators can be used to generate libraries suitable for fragment-based lead design (FBLD) directed at important metalloproteins.

Bidentate Zinc Chelators for α‐Carbonic Anhydrases that Produce a Trigonal Bipyramidal Coordination Geometry

Abstract: A series of new zinc binding groups (ZBGs) has been evaluated kinetically on 13 carbonic anhydrase (CA) isoforms. The fragments show affinity for all isoforms with IC(50) values in the range of 2-11 microM. The crystal structure of hCA II in complex with one such fragment reveals a bidentate binding mode with a trigonal-bipyramidal coordination geometry at the Zn(2+) center. The fragment also interacts with Thr199 and Thr200 through hydrogen bonding and participates in a water network. Further development of this ZBG should increase the binding affinity leading to a structurally distinct and promising class of CA inhibitors.

Hydrogen-bond rigidified BODIPY dyes

Abstract: Boron difluoride adducts of diamidodipyrromethenes have been synthesized and characterized. The compounds represent a new group of the BODIPY family of fluorescent dyes. X-ray crystallography and solution 19F NMR experiments show that a persistent hydrogen bond is formed between the boron-bound fluoride groups and the peripheral amide substituents. The modular synthesis of these compounds and their robust photophysical properties suggest that they may be useful compounds for materials and biological photochemical applications.

Primary care approach to dysphonia

Abstract: Objective To understand how primary care physicians manage patients with dysphonia and the barriers they face when evaluating patients for voice problems. Study Design Cross-sectional survey. Setting Primary care community. Subjects and Methods A total of 933 internal and family medicine physicians were randomly selected from a database of physicians in a referral basin of a tertiary care medical center and mailed a questionnaire. Questions concerned physician comfort level in recognizing an abnormal voice, their view of the quality of life impact of dysphonia, frequency of evaluating patients for voice problems, barriers to the evaluation of voice problems, reasons for referral, and common treatments prior to referral. Results A total of 271 physicians responded, for a response rate of 29.0 percent. Of those who responded, 36.5 percent routinely evaluate their patients for voice problems. Reasons for not evaluating patients for voice problems were patients not complaining about hoarseness, more pressing issues, not feeling comfortable assessing patients for voice problems, and time constraints. Chronic voice changes and not being able to understand patients' speech were the most common reasons for referral. Reflux and allergy treatment were common treatment modalities prior to referral. A total of 67.5 percent of respondents were interested in learning more about voice problems. Conclusion Primary care physicians face limitations with respect to evaluating patients for voice problems. Otolaryngologists must continue outreach efforts and collaboration with primary care colleagues in order to enhance the screening for voice problems.

Illuminating Metal Ion Sensors – Benzimidazolesulfonamide Metal Complexes

Abstract: The synthesis, structure, and solution spectroscopy of several (2-sulfonamidophenyl)benzimidazole metal complexes are reported. These ligands, which have been reported as selective molecular sensors for Zn(2+), readily form complexes with Co(2+), Ni(2+), Cu(2+), and Zn(2+). Surprisingly, the ligand adopts different binding modes depending on the metal ion. The work here provides insight into the coordination chemistry of these ligands, which may allow for the development of improved metal-ion sensors and metalloprotein inhibitors.

Acute dysphonia secondary to vocal fold hemorrhage after vardenafil use.

Abstract: Owing to their vasodilatory effects, the phosphodiesterase-5 inhibitors have become widely used for the treatment of erectile dysfunction. Among the reported adverse events of these agents are epistaxis, variceal bleeding, intracranial hemorrhage, and hemorrhoidal bleeding. We report a case of vocal fold hemorrhage that occurred after vardenafil use in a 31-year-old man who was a professional singer.

IceCube Collaboration Contributions to the 2009 International Cosmic Ray Conference

Abstract: IceCube Collaboration Contributions to the 2009 International Cosmic Ray Conference

Vocal fold injection as a treatment for glottic insufficiency: con.

Abstract: Correspondence: Clark A. Rosen, MD, University of Pittsburgh Voice Center, Department of Otolaryngology–Head and Neck Surgery, University of Pittsburgh Medical Center, Mercy Hospital, Building B, Ste 11500, 1400 Locust St, Pittsburgh, PA 15219 (rosenca@upmc.edu). Financial Disclosure: Dr Rosen is a consultant and medical bureau speaker for Bioform Medical Inc. He has been a recipient of grants from Bioform Medical for research into vocal fold injection materials.

Compliance and Quality of Life in Patients on Voice Rest

Abstract: on perceptive, acoustic and aerodynamic voice parameters. METHOD: We retrospectively reviewed the charts of patients treated in our department between 1998 and 2008 for sulcus vocalis and related lesions using the CO2-laser assisted endoscopic surgery with digital scanning, based on the technique described by Cornut and Bouchayer, and intraoperative collagen injection when vocal atrophy was present. Epidemiological data, perceptive, acoustic and aerodynamic parameters were collected at the preoperative and last follow-up visits and statistical analysis performed with the Wilcoxon signed rank test. RESULTS: There were 42 patients with a mean age of 41 years. Twenty-three patients had sulcus vocalis and nineteen had epidermoid vocal fold cysts. Seventeen patients had bilateral lesions. Collagen was injected for 9 patients. We observed a statistically significant improvement in the grade, roughness, and breathiness of the perceptual analysis according to Hiranos scale (G pre 2,G post 1, p 0.003) (R pre 2, R post 0, p 0.0020) (B pre 1, B post 0, p 0.003), in the Voice Handicap Index Score (VHI pre 53, VHI post 36, p 0.001). The maximal phonation time, phonatory quotient, jitter and frequency range were improved without reaching statistical significance. CONCLUSION: The CO2-laser scanning system seems a reliable option for the treatment of sulcus vocalis and related lesions based on perceptive and subjective data; however the objective improvement is harder to prove because surgery improves the vocal effort but does not induce normal looking and functioning vocal folds.

Modifying MOFs: New Chemistry, New Materials

Abstract: The postsynthetic modification (PSM) of metal–organic frameworks (MOFs) has grown substantially in the past few years. In this minireview, recent progress in the area of PSM is highlighted, with an emphasis on several recent advancements. The scope and limitations of PSM are described and future prospects are discussed.