Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor

A nanoscale optical biosensor based on localized surface plasmon resonance (LSPR) spectroscopy has been developed to monitor the interaction between the antigen, amyloid-beta derived diffusible ligands (ADDLs), and specific anti-ADDL antibodies. Using the sandwich assay format, this nanosensor provides quantitative binding information for both antigen and second antibody detection that permits the determination of ADDL concentration and offers the unique analysis of the aggregation mechanisms of this putative Alzheimer's disease pathogen at physiologically relevant monomer concentrations. Monitoring the LSPR-induced shifts from both ADDLs and a second polyclonal anti-ADDL antibody as a function of ADDL concentration reveals two ADDL epitopes that have binding constants to the specific anti-ADDL antibodies of 7.3 x 10(12) M(-1) and 9.5 x 10(8) M(-1). The analysis of human brain extract and cerebrospinal fluid samples from control and Alzheimer's disease patients reveals that the LSPR nanosensor provides new information relevant to the understanding and possible diagnosis of Alzheimer's disease.     

A convenient and efficient preparation of β-substituted α-haloenones from diazodicarbonyl compounds

Rhodium(II)-catalyzed reactions of cyclic diazodicarbonyl compounds with a variety of halides have been examined. With acid halides, β-acyloxy α-haloenones are produced in good yields. With benzyl halides, β-benzyloxy α-haloenones are obtained in good yields. Reactions with methylene halides yield β-halomethoxy α-haloenones in good yields, whereas reactions with ethyl halides and ethylene dihalides result in β-hydroxy α-haloenones in high yields. These reactions provide a useful and rapid entry to β-substituted α-haloenones. The mechanistic pathway for the formation of these products has been also described in terms of halonium ylides.     

RELATIVE REACTIVITIES OF THE EXCITED STATES OF FUROCOUMARINS FOR [2+2] PHOTOCYCLOADDITION REACTION WITH TETRAMETHYLETHYLENE

Abstract— The Stern-Volmer constants for fluorescence quenching by tetramethylethylene decrease in the order DMC ≫ DHP > F-2 > 8-MOP. The same order was observed for the quantum yields of [2+2] cycloaddition reaction with tetramethylethylene on direct irradiation. In [2+2] photocycloaddition of F-2 with tetramethylethylene in ethanol, the ratio of quantum yields deduced from singlet and triplet states of F-2; φ₃⁰/φ₁⁰, is about 5. The excited triplet state is the reactive state for the [2+2] photocycloaddition of F-2 with tetramethylethylene in solution but the excited singlet state of F-2 becomes very important in biological conditions.     

Subsolidus phase relations and crystal structure of compounds in the PrOx-CaO-CuO system

The subsolidus phase relations of the PrO_x-CaO-CuO pseudo-ternary system sintered at 950-1000°C have been investigated by X-ray powder diffraction. In this system, there exist one compound Ca₁₀Pr₄Cu₂₄O₄₁, one Ca₂Pr₂Cu₅O₁₀-based solid solution, seven three-phase regions and two two-phase regions. The crystal structures of Ca₁₀Pr₄Cu₂₄O₄₁ and Ca₂Pr₂Cu₅O₁₀-based solid solution have been determined. Compound Ca₁₀Pr₄Cu₂₄O₄₁ crystallizes in an orthorhombic cell with space group D_2h²⁰−Cccm, Z=4. Its lattice parameters are a=11.278(2) Å, b=12.448(3) Å and c=27.486(8) Å. The crystal structure of Ca₂Pr₂Cu₅O₁₀-based solid solution is an incommensurate phase based on the orthorhombic NaCuO₂ type subcell. The lattice parameters of the subcell of the Ca_2.4Pr_1.6Cu₅O₁₀ are a₀=2.8246(7) Å, b₀=6.3693(5) Å, c₀=10.679(1) Å, and those of the orthorhombic superstructure are with a=5a₀, b=b₀, c=5c₀. The Ca_2.4Pr_1.6Cu₅O₁₀ structure can also be determined by using a monoclinic supercell with space group C_2h⁵−P2₁/c, Z=4, a=5a₀, b=b₀, and β=104.79(1)° or 136.60(1)°, V=5a₀b₀c₀.     

On the Mavroyannis–Stephen relativistic long-range interaction energy term between optically active molecules

The relativistic long-range intermolecular interaction energy term of Mavroyannis and Stephen is estimated for some amino acids by using optical rotatory dispersion data and for hexahelicene by using theoretical values of excitation energies and rotational strengths. The result shows that the interaction energy may be significant for the interaction between some essentially dissymmetric chromophores such as hexahelicene, but that it is unimportant for other cases.     

Synthesis, dual fluorescence, and fluoroionophoric behavior of dipyridylaminomethylstilbenes

The synthesis, dual fluorescence, and fluoroionophoric behavior of two donor-sigma spacer-acceptor (D-s-A) compounds, trans-4-(N,N-bis(2-pyridyl)amino)methylstilbene (1H) and trans-4-(N,N-bis(2-pyridyl)amino)methyl-4'-cyanostilbene (1CN), are reported and compared to that of trans-4-(N,N-bis(2-pyridyl)amino)methyl-4'-(N,N-dimethylamino)stilbene (1DPA). To gain insights into the dual fluorescence properties for 1H and 1CN in polar but not in nonpolar solvents, model compounds resulting from a replacement of the stilbene group by alkyl (2R) or xylyl (2X) groups or from a replacement of the dipyridylamino (dpa) group by dianisoleamino (3AA), diethylamino (3EE), methylanilino (3MP), or diphenylamino (3PP) groups also have been investigated. In addition to 1H and 1CN, all four compounds of 3 display dual fluorescence. The locally excited (LE) fluorescence mainly results from the stilbene group and the ICT fluorescence from the through-bond interactions between the amino donor and the stilbene acceptors. In the presence of transition metal ions such as Zn(II), Ni(II), Cu(II), and Cd(II), the ICT processes are switched from dpa (D) --> stilbene (A) in 1H and 1CN to stilbene (D) --> dpa/metal ion (A) in their complexes. Whereas the ICT states for the complexes are generally nonfluorescent, an exception was found for the case of 1H/Zn(II). As a result, substituent-dependent fluoroionophoric behavior has been demonstrated by 1H, 1CN, and 1DPA in response to Zn(II).     

Insertion of a bis(phosphine)platinum group into the S-S bond of Mn(2)(CO)(7)(mu-S(2))

The reaction of Mn(2)(CO)(7)(mu-S(2)), 1, with Pt(PPh(3))(2)(PhC(2)Ph) yielded the new complex, Mn(2)(CO)(6)Pt(PPh(3))(2)(mu(3)-S)(2), 3, by loss of CO and insertion of a Pt(PPh(3))(2) group into the S-S bond of 1. Complex 3 was characterized crystallographically and was found to consist of an open Mn(2)Pt cluster with one Mn-Mn bond, 2.8154(14) A, one Mn-Pt bond, 2.9109(10) A, and two triply bridging sulfido ligands. Compound 3 reacts with CO to form adduct Mn(2)(CO)(6)(mu-CO)Pt(PPh(3))(2)(mu(3)-S)(2), 4. Compound 4 also contains an open Mn(2)Pt cluster with two triply bridging sulfido ligands but has only one metal-metal bond, Mn-Mn = 2.638(2) A. Under nitrogen, compound 4 readily loses CO and reverts back to 3.     

Single molecule force spectroscopy reveals the context dependent folding pathway of the C-terminal fragment of Top7

Top7 is a de novo designed protein with atomic level accuracy and shows a folded structure not found in nature. Previous studies showed that the folding of Top7 is not cooperative and involves various folding intermediate states. In addition, various fragments of Top7 were found to fold on their own in isolation. These features displayed by Top7 are distinct from those of naturally occurring proteins of a similar size and suggest a rough folding energy landscape. However, it remains unknown if and how the intra-polypeptide chain interactions among the neighboring sequences of Top7 affect the folding of these Top7 fragments. Here we used single-molecule optical tweezers to investigate the folding–unfolding pathways of full length Top7 as well as its C-terminal fragment (CFr) in different sequence environments. Our results showed that the mechanical folding of Top7 involves an intermediate state that likely involves non-native interactions/structure. More importantly, we found that the folding of CFr is entirely dependent upon its sequence context in which it is located. When in isolation, CFr indeed folds into a cooperative structure showing near-equilibrium unfolding–folding transitions at ∼6.5 pN in OT experiments. However, CFr loses its autonomous cooperative folding ability and displays a folding pathway that is dependent on its interactions with its neighboring sequence/structure. This context-dependent folding dynamics and pathway of CFr are distinct from those of naturally occurring proteins and highlight the critical importance of intra-chain interactions in shaping the overall energy landscape and the folding pathway of Top7. These new insights may have important implications on the de novo design of proteins.

Optical tweezers experiments reveal that the folding of the C-terminal fragment of Top7 (cFr) is context-dependent. Depending on its neighboring sequence, cFr shows very different folding pathways and folding kinetics.      

Hydrogen bonding and π–π stacking in 6‐hydroxy­biochanin A monohydrate

In the lattice of the title compound (systematic name: 5,6,7‐trihydroxy‐4′‐meth­oxy­isoflavone monohydrate), C₁₆H₁₂O₆·H₂O, the isoflavone mol­ecules are linked into chains through R₄³(17) motifs composed via O—H⋯O and C—H⋯O hydrogen bonds. Centrosymmetric R₄²(14) motifs assemble the chains into sheets. Hydrogen‐bonding and aromatic π–π stacking inter­actions lead to the formation of a three‐dimensional network structure.     

Imidazole-based excited-state intramolecular proton-transfer materials: synthesis and amplified spontaneous emission from a large single crystal

We have synthesized a novel class of imidazole-based excited-state intramolecular proton-transfer (ESIPT) materials, i.e., hydroxy-substituted tetraphenylimidazole (HPI) and its derivative HPI-Ac, which formed large single crystals exhibiting intense blue fluorescence and amplified spontaneous emission (ASE). Transparent, clear, and well-defined fluorescent single crystals of HPI-Ac as large as 20 mm x 25 mm x 5 mm were easily grown from its dilute solution. From the X-ray crystallographic analysis and semiempirical molecular orbital calculation, it was deduced that the four phenyl groups substituted into the imidazole ring of HPI and HPI-Ac allowed the crystals free from concentration quenching of fluorescence by limiting the excessive tight-stacking responsible for intermolecular vibrational coupling and relevant nonradiative relaxation. Fluorescence spectral narrowing and efficient ASE were observed in the HPI-Ac single crystal even at low excitation levels attributed to the intrinsic four-level ESIPT photocycle.