The synthesis of azacrown ethers with quinoline-based sidearms as potential zincII) ¯uorophores Guoping Xue, a Jerald S. Bradshaw, a,p N. Kent Dalley, a Paul B. Savage, a Reed M. Izatt, a Luca Prodi, b Marco Montalti b and Nelsi Zaccheroni b a Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602-4678, USA b Dipartimento di Chimica ªG. Ciamicianº, Universita di Bologna, Via Selmi 2, I-40126 Bologna, Italy Received 18 February 2002; revised 19 April 2002; accepted 22 April 2002 Abstract ÐTwo novel ¯uorophores, 12 and 13, composed of diaza-18-crown-6 ligands containing two quinoline-based sidearms which are structurally similar to ZnII) ¯uorophores TSQ 1) and Zinquin 2) were synthesized as potential ZnII) ¯uorophores by reductive amination of 8-benzenesulfonamido-2-quinoline carboxaldehyde 6 and 8-benzenesulfonamido-6-quinolyloxyacetate-2-carboxaldehyde 11 with diaza- 18-crown-6 using sodium triacetoxyborohydride NaBHOAc) 3 ) as the reducing agent. Preliminary photophysical properties of ligands 12 and 13 show that they possess the properties necessary to be effective chemosensors for Zn 21 . The solid state structure of 12 is also reported. q 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction Zinc is an essential element for humans and plays an impor- tant role in biochemical and nutritional processes. 1 Approxi- mately 300 enzymes contain zincII) as an essential component, either for structural purposes or as part of a catalytic site. 2 Furthermore, zinc is a global excess burden on the environment due to human activities. Increased levels of zinc are the result of smelting, re®ning, and manufactur- ing processes, but domestic waste waters also can contain high local zinc concentrations especially in aquatic eco- systems. 3 The level of zinc in seawater 3,4 is of importance since this metal meets the needs of many species for survival, and for the productivity of plankton. 5 Therefore, there is a need for reliable, fast, and low-cost methods for the quantitative analysis and monitoring of zinc levels in environmental and biological systems. While development of ¯uorescent chemosensors has been made for other biologically important divalent metal ions, in particular Ca 21 and Mg 21 with several selective ¯uoro- phores, 6 there are few Zn 21 selective ¯uorophores. Several quinoline-based compounds, such as 6-methoxy-8-p- toluenesulfonamido)-quinoline 1 TSQ) 7,8 and its ester ether derivative 2 Zinquin) 9 Fig. 1), are currently the most widely used zinc-activated ¯uorophores. However, for quantitative analysis of Zn 21 either in living cells or in other environments, TSQ and Zinquin are not satisfactory because they are not selective for Zn 21 but form complexes with many metal ions with varying ¯uorescence intensities. 10 A new type of selective and ef®cient Zn 21 ¯uorophore, a dansylamide-substituted macrocyclic tetraamine dansyl- amidoethylcyclen), has been developed by Kimura and co-workers. 11 Recently, we reported an ef®cient and convenient one-step method to introduce the dansyl chromophone onto macrocyclic polyamines. 12 The success of the dansylamidoethylcyclen ¯uorophore is due to a high af®nity of the aza macrocycle for Zn 21 , a strong af®nity for aromatic sulfonamides by the Zn 21 ±cyclen complex, and the strong luminescence property of the dansyl chromo- phore. Herein, we report the synthesis of two diaza-18- crown-6 ligands containing two quinoline-based sidearms which are structurally similar to TSQ 1 and Zinquin 2. We expected that attachment of TSQ or Zinquin analogues Tetrahedron 58 2002) 4809±4815 Pergamon TETRAHEDRON 0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII: S0040-402002)00451-9 Figure 1. Structure of zinc-active ¯uorophores. Keywords: chemosensors; ¯uorophores; crown ethers; quinoline; reductive amination. p Corresponding author. Tel.: 11-801-422-2415; fax: 11-801-422-0153; e-mail: jerald_bradshaw@byu.edu