We report a novel optical biosensor platform using near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWNTs) functionalized with target-recognizing aptamer DNA for noninvasively detecting cell signaling molecules in real-time. Photoluminescence (PL) emission of aptamer-coated SWNTs is modulated upon selectively binding to target molecules, which is exploited to detect insulin using an insulin-binding aptamer (IBA) as a molecular recognition element. We find that nanotube PL quenches upon insulin recognition via a photoinduced charge transfer mechanism with a quenching rate of kq = 5.85×1014 M−1s−1 and a diffusion-reaction rate of kr = 0.129 s−1. Circular dichroism spectra reveal for the first time that IBA strands retain a four-stranded, parallel guanine quadruplex conformation on the nanotubes, ensuring target selectivity. We demonstrate that these IBA-functionalized SWNT sensors incorporated in a collagen extracellular matrix (ECM) can be regenerated by removing bound analytes through enzymatic proteolysis. As proof-of-concept, we show that the SWNT sensors embedded in the ECM promptly detect insulin secreted by cultured pancreatic INS-1 cells stimulated by glucose influx and report a gradient contour of insulin secretion profile. This novel design enables new types of label-free assays and non-invasive, in-situ, real-time detection schemes for cell signaling molecules.

A ligand-modified, economical version of Stryker's reagent (SR) has been developed based on a bidentate, achiral bis-phosphine. Generated in situ, "(BDP)CuH" smoothly effects conjugate reductions of a variety of unsaturated substrates, including those that are normally unreactive toward SR. Substrate-to-ligand ratios typically on the order of 1000-10000:1 can be used leading to products in high yields.

COMMUNICATIONS TO THE EDITORVol. s2(V) bromide a t the temperature necessary for synthesis (ca. 100') keeps the yield very low and that

Substitution of a group such as chloro or methyl on the 5-position of the 4quinazolone moiety of the Hydrangea alkaloid has been found to have a favorable effect on the activity and the chemotherapeutic index (1, 2). In order to exploit this lead the fluoro, iodo, ethyl, propyl, trifluoromethyl, nitro, acetamino, methylthio, and methylsulfonyl groups were introduced into the 5-position.The fluoro derivative had an index and activity1 about the same as the 5-C1, whereas the iodo had a very low activity and index. When the methyl group was replaced by the larger ethyl or propyl groups the activity decreased in that order. These data indicate that a large group has an unfavorable action. However, trifluoromethyl had the highest index, 15, yet observed in analogs of the alkaloid, although the quinine coefficient was decreased to 35.These compounds were all prepared by condensation of the appropriately substituted 4-quinazolone with the blocked side chain, l-carbethoxy-2-(7-bromoacetonyl)-3-methoxypiperidine, followed by two-stage hydrolysis of the blocking groups as previously described (3).Six of the requisite 4-quinazolones were synthesized from the known 5-nitro-4quinazolone (4) via the readily available 6-nitroanthranilic acid (I) (5). 6-Iodo-2-nitrobenzoic acid (IV) was obtained in good yield from I, but all attempts to reduce this compound chemically or catalytically to 6-iodoanthranilic acid (VII)were unsuccessful. The steps were then reversed by reduction of 6-nitro-2formylaminobenzoic acid (VI) to VIII. Attempted replacements of the amino group with iodo through the diazonium salt were unsuccessful. The diazonium salt from I when treated with potassium ethyl xanthate gave 2-nitro-6-methylthiobenzoic acid (V) in low yield after methylation. All of the above difficulties were surmounted by the use of the diazonium salt from 5-amino-4-quinazolone (III). The 5-iodo derivative, IX, was obtained in 59% yield by treatment with potassium iodide. The 5-methylthio derivative (XI) was obtained with sodium methyl mercaptide in 71% yield and was oxidized to the sulfone, XII, with permanganate in dilute acetic acid. The use of sodium thiophenoxide gave XIII, but the procedure could not always be duplicated. The 5-fluoro derivative offered some difficulty since the diazonium fluoroborate was water-soluble. However, the diazonium fluoroborate could be isolated when the diazotization was carried out in 42% fluoroboric acid (6) to give an over-all yield of 56% of IX after pyrolysis in xylene.3-Nitrophthalic acid appeared attractive as a starting material for 5-ethyl-(XXIII) and 5-propyl-4-quinazolone (XXXIII). -Methyl hydrogen

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