“ High-Throughput ” Evaluation of Polymer-Supported Triazolic Appendages for Metallic Cations Extraction

The aim of this work was to find and use a low-cost high-throughput method for a quick primary evaluation of several metal extraction by substituted piperazines appendages as chelatants grafted onto Merrifield polymer using click-chemistry by the copper (I)-catalyzed Huisgen’s reaction (CuAAC) The polymers were tested for their efficiency to remove various metal ions from neutral aqueous solutions (13 cations studied: Li, Na, K, Mn, Fe, Co, Ni, Cu, Cd, Ba, Ce, Hg and Pb) using the simple conductimetric measurement method. The polymers were found to extract all metals with low efficiencies ≤40%), except for Fe and Hg, and sometimes Pb. Some polymers exhibited a selectively for K, Cd and Ba, with good efficiencies. The values obtained here using less polymer, and a faster method, are in fair correspondence (average difference ±16%) with another published evaluation by atomic absorption


Introduction
Water pollution by metallic ions and other pollutants is becoming an increasing concern nowadays.This modification of the water, in all his reservoirs, is mainly due to Human activities with uncontrolled rejects of such pollutants.The pollution has a strong impact onto the global ecosystem as well as drinkable water sources.There is thus a strong need for methods to analyze traces and to remove the pollutants from water.Usual methods for removing metallic salts from water range from distillation to the use of engineered materials such as zeolites, polymers, membranes, etc.The long time known ion-exchange resins can be used for this purpose [1][2][3].Usually, the polymers are engineered is such a way that their nature can be hydrophilic [4][5][6][7] or phobic [8,9], to meet the requirements for their use [10][11][12][13][14].Many polymers have been designed in order to include chelatants to fix metal ions to be used in applications such as purification, depollution or catalysis [15][16][17][18][19][20].
Due to our interest into metal chelation, supported catalysis and Huisgen's reaction, we became interested into the preparation of polymers based on this approach [21][22][23].We thus started to use the "click-chemistry" concept for polymer functionalization and especially copper (I)-catalyzed Huisgen's cycloaddition ("copper (I)-catalyzed azide/alkyne cycloaddition" or CuAAC) [24][25][26][27][28][29].The use of CuAAC has the advantage to give a quick access of controlled substitutions onto the polymer by the use of its azided version and alkynes with various substituents [30][31][32][33][34][35].This CuAAC is linking the azided polymer and the substituents bearing alkyne by forming the 1,4-triazole linkage.All the introduced substituents and the triazole can be implicated into chelation through a "triazole design", or a "pendant design", or both parts implicated into an "integrated design".The chelation can be a monoor multi-dentate mode due to the vicinity of other chelating entities and the flexible structure of the polymer chains.(Figure 1) [34,35].The goal of this work was to try to find a faster method, using less polymer, for the evaluation of several metal cations complexation evaluation.We present in this communication the use of the less sensitive conductimetric method for the study of piperazine-triazole-substituted poly(styrenes).The polymers were tested for their ability to extract metal cations salts (Li + , Na + , K + , Mn 2+ , Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , Cd 2+ , Ba 2+ , Ce 3+ , Hg + and Pb 2+ ) from neutral aqueous solutions.The results were found to be fair enough to be used for a primary evaluation at a "high-throughput" level when compared to our previous atomic absorption spectroscopy measurements (within ±16% average difference) [36].

N-Substituted Piperazine Propargylcarbamates and Polymers
Poly(azidomethylstyrene) was prepared from Merrifield polymer as already reported.N'-propargylcarbamates of N-substituted piperazine, and the corresponding polymers containing triazole-linked piperazines preparations were described in a another publication as depicted in Figure 2 [36,37].Typical procedures are indicated below.To a solution of the required N-substituted piperazine 1a to 1g (12.0 mmol) in acetonitrile (45 mL) was added Na2CO3 (1.27 g, 12.0 mmol, 1 eq.).Propargyl chloroformate (1.42 g, 1.17 mL, 12.0 mmol, 1 eq.) was then added dropwise.The reaction mixture was stirred for 48 h at room temperature and then filtered and evaporated under vacuum.The resulting carbamates 2a-2g were sufficiently pure to be used without further purification.

General procedure for the Synthesis of Polymers 3a-3g
Coupling reactions onto the polymer using CuAAC were conducted accordingly to the general procedure indicated below in round bottom flasks equipped with a reflux condenser.To a suspension of 3.00 g of azidomethyl polystyrene A (1.82 mmol N3 g −1 , 5.46 mmol N3) in THF (60 mL) was added 6.30 mmol (1.15 eq.) of the alkyne (2a-2g), 9.00 mL of triethylamine (6.75 g, 66,7 mmol, 12.2 eq.) and 2.40 mg of copper (I) iodide (12.6 µmol, 4 mol%).The suspension was slowly stirred at room temperature 72 h.After this time, the complete disappearance of the IR band of the azide of the polymer A (2103 cm −1 ) was observed.The resulting polymer was filtered on sintered glass and washed sequentially with CH2Cl2, pyridine, and MeOH (60 mL each), the sequential washings being repeated two other times.The resulting polymers 3a-3g were finally dried overnight in an oven at 50 °C.

Extraction Results
After 24 h incubation on a 100 mg scale of the polymers in 20 mL of 50 mg L −1 solutions of the salts (1 mg of salt, see Section 2.2.1 for details), the percentages of extraction for each metal were calculated by conductimetric differences between the initial and final solutions, each experiment having been carried out in triplicate.The results for each polymer as a function of the metallic cations are presented in Figure 3 (Section 2.2.2).
When looking at the whole results, we can observe than most of the cations were poorly extracted, at 30% or below, but exceptions.Since the polymeric structure differs only by the R substituent on the nitrogen (Figure 2, Section 2.1), an analysis has been done to understand the influence of the substituent's nature on the extraction.
From this first analysis, based only on the difference of the R group, it seems that the presence of an alkyl substituent (3a, R = Me, 3b, R = Et) is giving the best extraction levels for Fe 3+ and Hg + , probably due to the increased electronegativity of the amine.Inductive and steric hindrance effects can explain the differences between 3a and 3b.The introduction of a 2-methoxyphenyl group on the nitrogen (3c) changes it to an aniline, less basic, which is extracting less Fe 3+ and Hg + .However, the presence of the methoxy group in ortho position seems to help in Pb 2+ extraction.It is possible that this oxygenated group is implicated into the chelation of this metal.Replacement of this aromatic by a 2-pyrimidyl (3d) and 2-pyridyl (3e), less and more basic respectively when compared one to the other, still gives polymers capable of extracting Fe 3+ and Hg + , with similar levels as 3c.Special features of these polymers are higher extraction of K + for 3d and Ba 2+ for 3e, as well as exclusion of some cations: Li + , Na + , Mn 2+ , Co 2+ , Cu 2+ and Cd 2+ for 3d, and Ni 2+ and Ce 3+ for 3e.
The electronegativities and chelating capabilities of these amino-R groups are however difficult to put in relation with their extracting properties.The most puzzling effect is the presence of a benzylcarbamate onto the nitrogen of the polymer (3f).This group is totally modifying the properties of the polymer.In this case, more metallic ions are extracted, with the classical Fe 3+ and Hg + .This includes K + , Cd 2+ , Ba 2+ , and Pb 2+ .This may suggest another chelation mode introduced by the presence of the carbamate.Finally, the presence of a derivative of furoic acid as an amide on the nitrogen (3g) do not seems to helps since extraction levels are going down with extraction of the usual Fe 3+ , Hg + , and Pb 2+ , and exclusion of Li + , Na + , Cu 2+ .
The electronegativities of the substituted nitrogen of the piperazine can in part explain some of the relative extraction efficiencies.However, it is difficult to draw a clear conclusion.We have also tried to rationalize the interactions between the polymers and the metal ions based on their electropositivities, ionic radii and water solvatation.Once again, no clear link can be drawn about the extraction efficiencies based on the metal cation properties.The only difference that can explain, once again in part, the preference of the polymers for Fe 3+ and Hg + , and in some cases Pb 2+ , is the counter-ion of the salt used for the study.All metallic salts were chlorides except for Fe 3+ , Hg + , and Pb 2+ , which were used as their nitrates.
The final analysis we have tried to make is to try to find out the chelation mode from the piperazine-triazole in relation with the metal cations.For the best extraction results, over 40%, it was not possible to make a clear discrimination between the three modes (pendant, triazole and integrated).The ratios piperazine-triazole:metal cation varied from 13:1 (3f and K + , 67% ± 5%) to 118:1 (3e and Fe 3+ , 43% ± 2%), since the chelating moieties were in large excess.This cannot gives a clear hit on the chelation mode, which can be of polydentate type or simply a statistical repartition on the chelation sites, without knowledge of the chelation type.
All the results and analyses cannot clearly identify the discrete complexation behavior of the metal by the polymers at the solid/liquid interface.However, we were able to obtain better results than with our first series of triazolic polymers based on propargyl amides and propiolic anilides onto poly(styrene) [38].
Figure 4 presents our results by cation absorption to help to find the best extractant.By drawing a cut-off for selection at 40% extraction level, it is clear that none of the polymers is very efficient for the removal of Li + , Na + , K + , Co 2+ , Ni 2+ , Cu 2+ and Ce 3+ .For K + , polymer 3f is the best with 3.51 mg K + g −1 .
The conductimetric method used, even having a less precise reputation, was good enough to have a quick evaluation of several cations removal.This method has been selected both for its lower cost in appartatus when compared to AAS and ICP methods.It is also faster and easier to do the measurements in order to speed up the process to find the best and highly selective extractant for a range of engineered polymers.
Even if no clear interpretation can be done with the results for the interfacial chelation process, the good extraction properties encourage us to continue polymers modifications using CuAAC in order to find new polymeric complexants for depollution and catalytic applications.Further studies will be reported in due course.

Figure 2 .
Figure 2. Synthesis of the polymers by CuAAC procedure.