Combinatorial synthesis of fluorescent trialkylphosphine sulfides as sensor materials for metal ions of environmental concern

A combinatorial library of diverse alkyl-phosphine sulfides bound to Merrifield, Argopore, Argogel and Wang resins was synthesized and evaluated for their sensing properties. The library consists of 12 products with the anthranyl group as a fluorophore and phosphine sulfide alkyl derivatives as receptors of transition and heavy metal ions. The fluorescence spectral characteristics and the properties as sensing phase of these materials towards Pb(II) and Cu(II) were established.


Introduction
Solid phase organic synthesis is nowadays a well-established tool for the production of combinatorial libraries.While much research has been directed toward new drug and pharmaceuticals discovery, the field of developing new materials for chemical sensing has been scarcely addressed. 1Although this approach has achieved much progress, it suffers from disadvantages such as tedious and time-consuming procedures, low reproducibility and limited number of synthesized materials.With the advent of combinatorial chemistry a new strategy is currently emerging, which may increase the rate of investigation of chemical sensing materials. 2he attractiveness of this technique lies in the possibility of covering a desirable range of properties, in the large number of unique sensors that can be obtained each time, and in its dependence on the limited number of starting materials.
The production of sensing devices for the detection and measurement of different metal ions is of great importance in chemistry and biology.We have taken into account the growing interest in the synthesis of molecules capable of performing logical operations and their ability to detect the presence of transition and heavy metal ions. 3Most of the systems reported are based either on the quenching of fluorescence 4 or the enhancement of fluorescence. 5,6It is also known that the selective interaction of transition and heavy metal cations is achieved by receptors containing sulphur or nitrogen. 7,80][11] It has been demonstrated that the reaction equilibrium for the coordination of ligands to form a monomeric complex, is similar to that occurring internally with polymers which contain the same binding ligand. 12A polystyrene support was covalently bonded to the anthracene molecule which has been used as the fluorophore, and a phosphine sulfide group attached to anthracene as a recognizing receptor.
Recently, we developed a library of resin-dansyl-phenylboronic acids bound to Merrifield resin as selective sensors for fructose, which is 200 times more selective for fructose than glucose. 13ollowing with the search of novel sensors supported on solid phase, we have investigated the synthesis of fluorogenic receptors for copper and lead through a combinatorial approach.In this paper we describe the synthesis of a phosphine-sulfide-anthracene sensor library for Cu(II) and Pb(II) metal ions.According to the synthetic route outlined in Scheme 1, we chose three phosphine sulfide derivatives and four solid supports (Merrifield, Argopore, Argogel, and Wang resins).The fluorescence spectral characteristics of intermediates and final products supported on the various resins and their behavior as sensing phases were studied.The solids (3, 4, 5, 6, 7) were analyzed on a FIA system to determine the fluorescent response to the metals; only the product 7 showed to be sensitive to the presence of metal ion solutions.

Scheme 1
The library design shown in Table 1 represents a 3 × 4 array of metal ion sensing beads with diversity achieved with variations in the solid support and phosphine sulfide substituents.

Mass Spectra Analysis
Recently, a simple method for the analysis of polymer-supported species based on on mass spectrometry (MS) direct-insertion with electronic impact ionization was developed by our group. 17he conditions to operate the instrument such as high temperature and high vacuum, promote the thermal cleavage at the benzylic position of the resins.Polymer degradation does not interfere in the determination of the molecular weight of compounds attached to the resin.Polymer supported compounds 3a-d, 4a-d, and 5a-d were characterized by MS while still bound to the resins, avoiding time-consuming liberations.

Fluorescence characteristics
The fluorescence spectral behavior of intermediates 4 and 5, and the final material 7 (Scheme 1), was studied in order to evaluate the influence of the pendant group on the anthracene moiety.Fluorescence intensities at the maximum excitation and emission wavelengths were recorded and are plotted in Figure 1.As can be seen, the general trend is similar in all the materials assayed: a continuous decrease in fluorescence intensity going from the -OH group (I) through the -Cl (II) to the i-butylphosphine sulfide (III).This effect could be ascribed to an intramolecular heavy atom effect.Also, a decrease on the fluorescent intensity is observed as the withdrawing effect of the pendant group increases.It is important to notice that the alkyl groups on the phosphine sulfide moiety also play a role in the luminescence properties of the final materials.In fact, as shown in Figure 2 for the Merrifield-based phosphine sulfide materials, the fluorescence is enhanced for the i-butyl group.A possible explanation for this effect could be the proximity of methyl groups to the phosphine sulfide centre, the spacer between them being shorter in the case of i-butyl.The proximity of methyl groups seems to reverse the heavy atom effect observed above for the phosphine sulfide group.The spectral shape for all the sensing phosphine sulfide beads does not depend on the solid support used and follows the same trend; only the fluorescence spectra of the Merrifield-based phosphine sulfide sensing beads are shown in Figure 2. The spectra do not show the pattern of the structured bands of the anthracene moiety.Both excitation and emission spectra are red shifted.A possible explanation could be the formation of intramolecular excimers among anthracene moieties.To validate these results, we tested intermediates 3, 4, 5, 6, 7a-d.Only the resin-phosphine sulfide products 7a-d showed positive response (Figure 3).
The properties of these materials as sensing phases were studied as packing beads into a conventional flow-through cell.Metal ions introduced by flow injection produce a quenching of fluorescence and the response is reversible.Figure 3 shows the analytical results for copper determination in a FIA approach with detection limits of 41 µg/mL (Cu) and 53 µg/mL (Pb), repeatability of 2 % and 4 % (at 100 µg/mL Cu and Pb level), respectively, and linear calibration up to 200 µg/mL for Cu(II) and 300 µg/mL for Pb(II).Reversible quenching signals were observed for copper at pH 7.7 and for lead at pH 2.0.Therefore, this sensing material may be used as selective recognition sensing phase for these metals ions.

Conclusions
A combinatorial library of diverse alkyl-phosphine sulfides bound to different solid supports was synthesized and their physical-chemical properties evaluated.It was found that the nature of the phosphine sulfide alkyl group plays an important role in the fluorescence quantum yield of the anthraquinone-based luminescent materials, while the solid support seemed to be of minor influence.The obtained phosphine sulfide-anthracene resins could be used as a selective recognition sensing phase for Pb(II) and Cu(II).

Experimental Section
General Procedures.The Merrifield (1.19 mmol/g), Wang (1.21 mmol/g), Argopore (0.96 mmol/g) and Argogel (0.47 mmol/g) resins were purchased from Aldrich Chem.Co. Melting points were determined on an Electrothermal 88629 apparatus and are uncorrected.Infrared (IR) spectra were taken on a Perkin Elmer FT-IR 1600 spectrometer. 1H and 13 C nuclear magnetic resonance spectra were recorded on a Varian Mercury 200 MHz Spectrometer in CDCl 3 with TMS as internal standard.Mass spectra were obtained on a Hewlett Packard 5989 MS Spectrometer at 70 eV by direct insertion.ESI Mass Spectra were obtained on a Agilent 1100 MSD Ion Trap spectrometer.Elemental Analyses were performed by Numega Resonance labs.San Diego, CA.Combinatorial Chemistry was carried out in a Quest Reactor Argonaut model SLN-210.The Fluorescence spectra were obtained on a Shimadzu RF-5301 PC spectrometer.

Figure 2 .
Figure 2. Influence of the alkyl groups bound to the phosphine sulfide moiety on the fluorescence intensity of the sensing Merrifield beads.

Figure 3 .
Figure 3. Flow Injection Analysis for Merrifield-phosphine sulfide sensors at three different concentrations of Cu (II) standard solutions.

Table 1 .
Library design