3,242 research outputs found
From 2,3-Diazabicyclo[2.2.2]oct-2-ene to Fluorazophore-L, a membrane-bound fluorescent probe for antioxidants
The aim of this work was to synthesize and to establish a new fluorescent membrane
probe for antioxidants by exploiting the exceptional properties of the long-lived
fluorophore 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) alias Fluorazophore-P.
The first step was to find an appropriate synthetic route towards a lipophilic derivative
of Fluorazophore-P, namely Fluorazophore-L, that should enable an efficient and facile
incorporation into model membrane systems. The water-soluble hydroxy-substituted
Fluorazophore-H was chosen as a key compound and served as a versatile precursor for
various members of the Fluorazophore-family, including Fluorazophore-L. For example,
substantial contributions in the synthesis of fluorazophore-labeled peptides to monitor the
length-dependence of end-to-end collision rates of polypeptides were done within this
work: "A Fluorescence Based Method for Direct Measurement of Submicrosecond
Intramolecular Contact Formation in Biopolymers: An Exploratory Study with
Polypeptides", R. R. Hudgins, F. Huang, G. Gramlich, W. M. Nau, J. Am. Chem. Soc.
2002, 124, 556-564. (Appendix)
In this context, the search for a mild and selective method to substitute a harsh
hydrolysis step, led to a study about a photo-cleavable Fluorazophore: "A Photoactivable
Fluorophore Based on Thiadiazolidinedione as Caging Group", G. Gramlich, W. M.
Nau, Org. Let. 1999, 1, 603-605. (Appendix)
Fluorazophore-L (Fluoazophore-L) was designed as a head-labeled palmitic acid
derivative. Experiments in homogeneous solution confirmed that Fluoazophore-L
preserves its photophysical properties, namely the long-lived fluorescence and the
essentially diffusion-controlled reactivity towards α-tocopherol (α-Toc). Its capability to
serve as a membrane probe was assessed by air/water monolayer experiments (surface
pressure-area isotherms) and preliminary spectroscopic measurements. It could be shown
that Fluoazophore-L partitions into monolayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-
phosphocholine (POPC) and that even pure Fluoazophore-L forms stable monolayers at
the air-water interface thus presents a highly amphiphilic molecule: "A Long-Lived
Amphiphilic Fluorescent Probe studied in POPC Air-Water Monolayer and Solution
Bilayer Systems", G. Gramlich, J. Zhang, M. Winterhalter, W. M. Nau, Chem. Phys.
Lipids 2001, 113, 1-9 (Appendix). The first assignment of Fluoazophore-L in model membranes was a study of its
interaction with the water-soluble antioxidant vitamin C, thus examining interfacial
reactivity. Singlet-excited Fluoazophore-L was used as a mimic for highly reactive lipid
alkoxyl and peroxyl radicals. This work revealed an unexpected inversion of the pHdependent
activity pattern, which could be ascribed to an interesting surface effect:
"Increased Antioxidant Reactivity of Vitamin C at low pH in Model Membranes", G.
Gramlich, J. Zhang, W. M. Nau, J. Am. Chem. Soc. 2002, 124, 11252-11253 (Appendix).
Finally, the intrafacial reactivity of α-Toc in liposomes and micelles could be probed
by means of Fluoazophore-L. In micelles and in membrane structures a more demanding
quenching kinetics than in usual organic solvents arises. In the case of small micelles
Poissonian statistics has to be applied while in liposomes a two dimensional diffusion
rate limits the maximum reactivity. In this study, the "immobile" probe/quencher pair
Fluoazophore-L/α-Toc was used for the first time and the validity of different quenching
models was discussed. The resulting diffusion rate constants for α-Toc provide important
benchmark values for antioxidant research: "Diffusion of α-Tocopherol in Membrane
Models: Probing the Kinetics of Vitamin E Antioxidant Action by Fluorescence in Real
Time", G. Gramlich, J. Zhang, W. M. Nau, J. Am. Chem. Soc. 2004, 126, 5482-5492
(Appendix).
A global fitting routine was developed to allow appropriate data processing of
fluorescence quenching in membrane models. This fitting procedure was also
successfully employed in the simultaneous fitting of steady-state and time-resolved
fluorescence quenching by host-guest complexation with cyclodextrins. "A Joint
Structural, Kinetic, and Thermodynamic Investigation of Substituent Effects on Host-
Guest Complexation of Bicyclic Azoalkanes by β-Cyclodextrin", X. Zhang, G. Gramlich,
X. Wang, W. M. Nau, J. Am. Chem. Soc. 2002, 124, 254-263 (Appendix).
For the quenching models used, it is essential to ensure that reaction between singletexcited
fluorazophores and hydrogen donors as antioxidants occurs only by hydrogen
transfer and upon contact of probe and quencher. To clarify this process experiments
using spectroscopic methods were contributed to a detailed theoretical study of reaction
pathways: "Fluorescence Quenching by Sequential Hydrogen, Electron, and Proton
Transfer in the Proximity of a Conical Intersection", A. Sinicropi, R. Pogni, R. Basosi, M. A. Robb, G. Gramlich, W. M. Nau, M. Olivucci, Angew. Chem., Int. Ed. 2001, 40,
4185-4189 (Appendix).
In summary, the result of this study was the design and synthesis of the new
fluorescent membrane probe Fluorazophore-L that combines the unusual properties of
DBO with a complete incorporation into model membranes. The properties of the new
probe were assessed in monolayer and by fluorescence lifetime experiments. Its potency
was proven by the interaction with natural antioxidants located in the proximity of
membrane mimetic systems. These quenching experiments allowed a new insight into the
processes involving antioxidants in microheterogeneous environments, especially an
unusual inversion of the well-known reactivity pattern of ascorbic acid and the
observation of the lateral diffusion of α-tocopherol along the surface of supramolecular
assemblies
America's Second Housing Boom
Reviews trends in the U.S. housing market, including homeownership rates, prime and subprime mortgages, and mortgage denial rates by race/ethnicity; and studies on the benefits of homeownership. Discusses implications and recommended policy measures
Quality Work-Based Learning and Postschool Employment Success
Many students with disabilities continue to struggle to successfully make the transition from school to employment. Despite advances in employment rates for students with disabilities who have exited school, their employment rates still lag significantly behind their nondisabled peers (Blackorby & Wagner, 1996). For decades, research has shown the strong relationship between work experience during secondary school and postschool employment for youth with disabilities (Benz, Yovanoff, & Doren, 1997; Colley & Jamison, 1998; Hasazi, Gordan, & Roe, 1985). However, as the continuing disappointing postschool employment rates for youth with disabilities suggest, there remains a critical need to expand work-based learning opportunities for these youth and to integrate these experiences into secondary education. This brief highlights the benefits of work-based learning, what constitutes quality work-based learning, and selected evidence-based models of work-based learning
Booms and busts: the case of subprime mortgages
Booms and busts have played a prominent role in American economic history. In the 19th century, the United States benefited from the canal boom, the railroad boom, the minerals boom, and a financial boom. The 20th century brought another financial boom, a postwar boom, and a dot-com boom. ; The details differed, but each of these cases featured initial discoveries or breakthroughs, widespread adoption, widespread investment, and then a collapse where prices could not keep up and many investors lost a lot of money. When the dust cleared, there was financial carnage and many investors learning to be more careful the next time. But fruits of the boom were still around to benefit productivity. ; The late Edward M. Gramlich prepared the luncheon address for the Federal Reserve Bank of Kansas City’s 2007 symposium last summer in Jackson Hole, Wyoming. This article, based on his speech, describes why he believed the subprime lending market, despite its problems, is a promising development that has permitted low-income and minority borrowers to participate in credit markets.Subprime mortgage ; Mortgage loans
How should public infrastructure be financed?
Infrastructure (Economics) ; Finance ; Public policy
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