A Pb²⁺-binding polychelatogen derived from thionated lactide

Abstract

The synthesis and characterization of a polychelatogen derived from thionated lactide is reported. The four step synthesis from L-LA requires thionation and thia-Diels–Alder steps to afford a highly strained spiro-lactone adduct that is amenable to ring-opening metathesis polymerization. Saponification of the polymer affords a polyanion that exhibits a high affinity for toxic Pb²⁺ in aqueous solutions, results that we attribute to thioether and hydroxy carboxylate chelating moieties that are integrated into the polymer backbone and residues respectively.

---

Polychelatogens are a class of non-crosslinked water-soluble polymers that exhibit metal ion complexation capabilities.¹ Materials such as these belong to a broader set of polymer-based reagents² that are designed to sequester heavy metal contaminants in water resources that pose a risk to human health.³ In light of ongoing efforts to improve water quality⁴ in parts of the world where potable water is scarce,⁵ the quest for improved metal-sequestration technologies remains increasingly important if inexpensive and clean water is to be available on a global scale. In this communication, we report on a novel polychelatogen comprised entirely of thioether⁶ and hydroxy carboxylate⁷ chelators that are well known for their affinity to coordinate metal ions. Key to this work is the synthesis of a mono-thionated lactide that is capable of thia-Diels–Alder cycloadduct formation with cyclopentadiene. Ring-opening metathesis polymerization (ROMP) of the norbornene-like monomer affords a polythioether with spiro-lactone residues that are saponified to their corresponding hydroxy carboxylates. The polyanion is shown to possess a high affinity for Pb²⁺ in aqueous solution, results that we attribute to a coordination site architecture that employs both the polymer backbone and anionic residue of each constituent repeat unit.

While the ring-opening polymerization of lactide (LA) to poly(lactide) (PLA) is well documented,⁸ the derivatization of lactide as a platform to other polymers is extremely rare.⁹ In this work, thionoester 1 was prepared according to Scheme 1 by reacting L-LA with a reagent combination of phosphorous pentasulfide (P₄S₁₀) and hexamethyldisiloxane (HMDO).¹⁰ Single-crystal X-ray diffraction (XRD) studies confirmed the proposed structure, revealing two independent molecules in the asymmetric unit (Z = 8, Fig. 1a) with C=S (ca. 1.617(2) and 1.621(2) Å) and C=O bond distances (ca. 1.193(3) and 1.196(3) Å) that are in line with literature values.¹¹ Likewise, the distinct methine and methyl environments of 1 are supported by the: (i) quartet (δ = ca. 4.94–5.06 ppm) and doublet (δ = ca. 1.56–1.77 ppm) pairs observed in the ¹H NMR spectrum (Fig. S1†) and (ii) ¹³C resonances at δ = ca. 211.5 and 167.6 ppm (Fig. S2†) that are indicative of thionoester and ester carbonyl groups respectively. Perhaps most importantly, characterization by way of chiral high-performance liquid chromatography (Fig. S7 and S8†) and polarimetry indicate that epimerization does not occur to a significant extent during the process of thionation, hence enantiomerically pure and racemic 1 can be prepared directly from the appropriate lactide stereoisomer(s).¹²

Scheme 1 Synthesis of poly-2b from L-lactide.

Fig. 1 Representation (50% thermal ellipsoids) of the X-ray crystal structure of: (a) 1 (view down the a-axis of the unit cell) and (b) 2. Hydrogen atoms are omitted for clarity. Key: C = gray, O = red, and S = yellow.

In a seminal work reported by Jing and Hillmyer,^9a lactide-derived (6S)-3-methylene-6-methyl-1,4-dioxane-2,5-dione was heated with cyclopentadiene to afford a diastereotopic mixture of bicyclic Diels–Alder products that were used to prepare PLA composites with improved toughness. In this work, heating 1 with cyclopentadiene¹³ affords a mixture of thia-Diels–Alder products from which the major cycloadduct 2 can be separated via crystallization from hot hexanes. X-ray crystallographic data (Fig. 1b) revealed that the sulfur atom is located over the least sterically encumbered face of the lactone ring, indicating a mechanism whereby the methyl groups of the dieneophile are positioned on the same side as the approaching diene. Despite the steric congestion about the lactone moiety, its conversion into the hydroxy carboxylate derivative was demonstrated as a proof-of-principle by saponifying 2 in aqueous NaOH (1.1 mol equiv. NaOH) until its complete dissolution. The identity of 3 was unequivocally confirmed by NMR spectroscopy (Fig. S11–S14†) and high-resolution electrospray ionization mass spectrometry where peak masses of ca. 289.049, 555.111, and 821.172 are consistent with monomer (calcd for [3 + Na]⁺, 289.048), dimer (calcd for [(3)₂ + Na]⁺, 555.107), and trimer adducts (calcd for [(3)₃ + Na]⁺, 821.165) with an additional sodium ion (Fig. S15†). Incredibly, treatment of 3 with 1 M aqueous HCl regenerated 2 quantitatively (Fig. S16†) suggesting that the coordination sites in our target polymer may be deactivated upon application of a pH stimulus.

Encouraged by a report on the synthesis of sodium poly(7-oxanorbornene-2-carboxylate) from its methyl ester precursor,¹⁴ we elected to prepare polyanion poly-2b by saponification of poly-2a (Scheme 1). In this regard, monomer 2 was polymerized by ROMP using 2^nd generation Grubbs' catalyst (Ru)¹⁵ at monomer-to-catalyst ratios (i.e. [2]₀/[Ru]₀) listed in Table 1. In line with the proposed structure, the ¹H NMR spectra of poly-2a (Fig. S17–S20†) possess broad resonances at δ ca. 5.73 ppm that are consistent with the methylylidene proton environments common among norbornene-based polymers.¹⁶ It should be noted that while GPC traces (Fig. S21–S24†) are predominantly monomodal with dispersities Đ_M in the range of 2.0–2.2, molecular weight control by way of adjusting [2]₀/[Ru]₀ was not observed under the conditions employed here. Nonetheless, the thermal properties among the high molecular weight polymers are near identical with glass transition temperatures T_gs at ca. 142 °C and thermal decomposition temperatures T_decs spanning ca. 306–310 °C (Table 1). Poly-2a was subsequently saponified into the polyanion poly-2b by stirring in a THF/aqueous NaOH (1 M) mixture followed by dialysis against a 3.5 kDa MWCO in deionized water to remove excess hydroxide anion.

Table 1 ROMP of 2 by 2^nd generation Grubbs' catalyst (Ru)

[2]0/[Ru]0	Mn^a (kg mol^−1)	ĐM	Tg^b (°C)	Tdec^c (°C)
a Determined by GPC (relative to polystyrene in THF).b Glass transition temperature, second heating curve, determined by DSC.c Decomposition temperature, onset, determined by TGA.
100	51.1	2.1	142	306
200	68.6	2.1	142	306
400	135.4	2.0	141	308
800	142.8	2.2	141	310

---

In our preliminary investigation into the liquid-phase polymer-based retention (LPR)^1a of Pb²⁺, aqueous solutions of poly-2b (2 mL, [poly-2b] = ca. 1 mg mL⁻¹) and Pb²⁺ (1 mL, [Pb²⁺] = ca. 30 ppm) were combined ([poly-2b], ca. 0.67 mg mL⁻¹; [Pb²⁺]₀, ca. 10 ppm) and stirred under ambient conditions for 90 min followed by centrifugation through a commercially available Amicon Ultra filter equipped with a regenerated cellulose membrane (3 kDa MWCO). Filtrate analysis by atomic absorption spectroscopy revealed no detectable Pb²⁺ in these solutions (Fig. S36,† n = 3), even after several retentate washes (e.g., 5 × 3 mL) with deionized water (Fig. S37†). Indeed, filtrates from control experiments employing polymer-free solutions were found to possess Pb²⁺ concentrations of ca. 9.57 ± 0.08 ppm (Fig. S38,† n = 3) indicating that the cellulose membrane did not play a significant role in Pb²⁺ binding. As anticipated from earlier results, washing the membrane with three aliquots of 1 M HCl (3 mL) afforded filtrates with [Pb²⁺] of 7.09, 1.63, and 0.21 ppm respectively indicating that Pb²⁺ can be released from the polymer upon treatment with aqueous acid. As an extension of this work, filtrates from aqueous formulations ([poly-2b] = ca. 0.1 mg mL⁻¹), [Pb²⁺]₀ (ca. 9 ppm) spiked with: (i) Na⁺ (ca. 10 ppm), (ii) K⁺ (ca. 10 ppm) or (iii) Ca²⁺ (ca. 10 ppm) were found to have Pb²⁺ concentrations of 0.12 ± 0.01, 0.14 ± 0.01, and 0.21 ± 0.06 ppm respectively (Fig. S39,† n = 3), indicating that these alkali/alkaline earth metal ions commonly found in natural waters do not impede Pb²⁺ coordination to a significant extent at these concentrations.

To gain further insight into Pb²⁺ uptake by poly-2b, Pb²⁺ retention (%) was measured as a function of the initial Pb²⁺ concentration [Pb²⁺]₀ (Fig. 2). Indeed, a near quantitative retention of Pb²⁺ by the polychelatogen ([poly-2b] = ca. 0.1 mg mL⁻¹). pH = ca. 6, n = 3 in solutions up to [Pb²⁺] ca. 50 ppm was observed, after which the Pb²⁺ retention drops considerably as the retentate solutions become turbid. Be that as it may, the binding capacity Pb²⁺ in milligrams per gram of poly-2b at [Pb²⁺]₀ = 150 ppm is ca. 2481.9 ± 158.4 mg (Pb²⁺) per g (poly-2b), a value that is among the highest reported to date.^2b,17 Moreover, [poly-2b] concentrations could be increased to promote the near quantitative retention of Pb²⁺ from solutions of ca. [Pb²⁺]₀ = 100 ppm (Fig. S40†), indicating that the LPR system can be optimized to enhance performance.

Fig. 2 Retention (%) of Pb²⁺ as a function of [Pb²⁺]₀. Data is reported as a mean with standard deviation (n = 3). [poly-2b] = 0.033 mg mL⁻¹, pH = ca. 6.

In summary, we report on the synthesis and characterization of a thionated lactide and its conversion to a spiro-lactone adduct that can be isolated in an isomerically pure form. The norbornene-like monomer can be polymerized and subsequently saponified into a poly(thioether) with hydroxy carboxylate residues, moieties that contribute to the polymer's Pb²⁺-binding capacity that is to the best of our knowledge, among the highest reported to date. On the bases of the results reported here, binding studies as a function of mixed (heavy) metal ion composition, pH, polymer stereochemistry, and comonomer composition are currently underway.

Acknowledgements

The authors thank Prof. Stacey Brenner-Moyer and her group for the use of their LC instrument. The authors also thank Rutgers University for financial support and the NSF for funds used to purchase our Bruker ASCEND 500 MHz spectrometer (NSF MRI 1229030).

References

1. (a) B. Y. Spivakov, K. Geckeler and E. Bayer, Nature, 1985, 315, 313–315; (b) K. E. Geckeler, V. M. Shkinev and B. Y. Spivakov, Angew. Makromol. Chem., 1987, 155, 151–161; (c) M. Tülü and M. Senel, J. Appl. Polym. Sci., 2008, 109, 2808–2814.
2. For examples, see: (a) S. D. Alexandratos and X. Zhu, New J. Chem., 2015, 39, 5366–5373; (b) S. D. Alexandratos and S. Natesan, Macromolecules, 2001, 34, 206–210; (c) C. A. Bell, S. V. Smith, M. R. Whittaker, A. K. Whittaker, L. R. Gahan and M. J. Monteiro, Adv. Mater., 2006, 18, 582–586; (d) B. L. Rivas and A. Maureira, Inorg. Chem. Commun., 2007, 10, 151–154; (e) E. Ramírez, S. G. Burillo, C. Barrera-Díaz, G. Roa and B. Bilyeu, J. Hazard. Mater., 2011, 192, 432–439; (f) T. Tomida, K. Hamaguchi, S. Tunashima, M. Katoh and S. Masuda, Ind. Eng. Chem. Res., 2001, 40, 3557–3562.
3. L. Järup, Br. Med. Bull., 2003, 68, 167–182.
4. World Health Organization, Guidelines for Drinking-water Quality, Gutenberg, Malta, 4th edn, 2011.
5. (a) M. Elimelech and W. A. Phillip, Science, 2011, 712–717; (b) M. A. Shannon, P. W. Bohn, M. Elimelech, J. G. Georgiadis, J. Mariñas and A. M. Mayes, Nature, 2008, 452, 301–310; (c) M. R. Hartono, A. Assaf, G. Thouand, A. Kushmaro, X. Chen and R. S. Marks, Water, Air, Soil Pollut., 2015, 226, 1–11.
6. (a) S. G. Murray and F. R. Hartley, Chem. Rev., 1981, 81, 365–414; (b) A. M. Masdeu-Bultó, M. Diéguez, E. Martin and M. Gómez, Coord. Chem. Rev., 2003, 242, 159–201.
7. (a) S. Paria, S. Chatterjee and T. K. Paine, Inorg. Chem., 2014, 53, 2810–2821; (b) T. K. Paine, S. Paria and L. Que Jr, Chem. Commun., 2010, 46, 1830–1832; (c) C. M. Cawich, A. Ibrahim, K. L. Link, A. Bumgartner, M. D. Patro and S. N. Mahapatro, Inorg. Chem., 2003, 42, 6458–6468; (d) R. Codd and P. A. Lay, J. Am. Chem. Soc., 1999, 121, 7864–7876; (e) S. M. Saadeh, M. S. Lah and V. L. Pecoraro, Inorg. Chem., 1991, 30, 8–15; (f) E. B. Kipp and R. A. Haines, Inorg. Chem., 1972, 11, 271–276; (g) R. A. Haines and A. A. Smith, Inorg. Chem., 1973, 12, 1426–1428; (h) F. Cariati, F. Morazzoni and G. M. Zanderighi, Inorg. Chim. Acta, 1977, 21, 133–1440; (i) A. Fishinger, A. Sarapu and A. Companion, Can. J. Chem., 1969, 47, 2629–2637; (j) Y. Zhang, I. Karatchevtseva, F. Kadi, B. Yoon, J. R. Price, F. Li and G. R. Lumpkin, Polyhedron, 2015, 87, 377–382.
8. (a) Y. Sarazin and J. F. Carpentier, Chem. Rev., 2015, 115, 3564–3614; (b) J. M. Becker, R. J. Poundera and A. P. Dove, Macromol. Rapid Commun., 2010, 31, 1923–1937; (c) O. Dechy-Cabaret, B. Martin-Vaca and D. Bourissou, Chem. Rev., 2004, 104, 6147–6176; (d) M. J. Stanford and A. P. Dove, Chem. Soc. Rev., 2010, 39, 486–494; (e) C. M. Thomas, Chem. Soc. Rev., 2010, 39, 165–173.
9. (a) F. Jing and M. A. Hillmyer, J. Am. Chem. Soc., 2008, 130, 13826–13827; (b) G. Fiore, F. Jing, V. G. Young Jr, C. J. Cramer and M. A. Hillmyer, Polym. Chem., 2010, 1, 870–877; (c) J. A. Castillo, D. E. Borchmann, A. Y. Cheng, Y. Wang, C. Hu, A. García and M. Weck, Macromolecules, 2012, 45, 62–69; (d) G. M. Miyake, Y. Zhang and E. Y.-X. Chen, J. Polym. Sci., Part A: Polym. Chem., 2015, 53, 1523–1532; (e) T. C. Mauldin, J. T. Wertz and D. J. Boday, ACS Macro Lett., 2016, 5, 544–546.
10. (a) T. J. Curphey, J. Org. Chem., 2002, 67, 6461–6473; (b) T. J. Curphey, Tetrahedron Lett., 2002, 43, 371–373.
11. F. H. Allen, O. Kennard and D. G. Watson, J. Chem. Soc., Perkin Trans. 2, 1987, S1–S19.
12. Trace amounts of dithionated lactide can be isolated during the purification of 1. See ESI† for details.
13. V. M. Timoshenko, S. A. Siry, A. B. Rozhenko and Y. G. Shermolovich, J. Fluorine Chem., 2010, 131, 172–183.
14. (a) M. Wathier, B. A. Lakin, P. N. Bansal, S. S. Stoddart, B. D. Snyder and M. W. Grinstaff, J. Am. Chem. Soc., 2013, 135, 4930–4933; (b) M. Wathier, S. S. Stoddart, M. J. Sheehy and M. W. Grinstaff, J. Am. Chem. Soc., 2010, 132, 15887–15889.
15. M. Scholl, S. Ding, C. W. Lee and R. H. Grubbs, Org. Lett., 1999, 1, 953–965.
16. For examples, see: (a) H. A. Kang, H. E. Bronstein and T. M. Swager, Macromolecules, 2008, 41, 5540–5547; (b) H. Gu, R. Ciganda, R. Hernandez, P. Castel, P. Zhao, J. Ruiz and D. Astruc, Macromolecules, 2015, 48, 6071–6076; (c) D. J. Liaw, J. S. Tsai and P. L. Wu, Macromolecules, 2000, 33, 6925–6929.
17. For examples, see: (a) J. J. Alcaraz-Espinoza, A. E. Chávez-Guajardo, J. C. Medina-Llamas, C. A. S. Andrade and C. P. de Melo, ACS Appl. Mater. Interfaces, 2015, 7, 7231–7240; (b) C. J. Madadrang, H. Y. Kim, G. Gao, N. Wang, H. Feng, M. Gorring, M. L. Kasner and S. Hou, ACS Appl. Mater. Interfaces, 2012, 4, 1186–1193; (c) Y. L. F. Musico, C. M. Santos, M. L. P. Dalida and D. F. Rodrigues, J. Mater. Chem. A, 2013, 1, 3789–3796; (d) E. Ramirez, S. G. Burillo, C. B. Diaz, G. Roa and B. Bilyeu, J. Hazard. Mater., 2011, 192, 432–439; (e) X. Wang, M. Min, Z. Liu, Y. Yang, Z. Zhou, M. Zhu, Y. Chen and B. S. Hsiao, J. Membr. Sci., 2011, 379, 191–199; (f) A. Mahapatra, B. G. Mishra and G. Hota, J. Hazard. Mater., 2013, 258–259, 116–123; (g) H. Bessbousse, T. Rhlalou, J. F. Verchere and L. Leburn, J. Membr. Sci., 2008, 307, 249–259; (h) Y.-H. Li, J. Ding, Z. Luan, Z. Di, Y. Zhu, C. Xu, D. Wu and B. Wei, Carbon, 2003, 41, 2787–2792; (i) S. Tolani, A. Mugweru, M. Craig and A. K. Wanekaya, J. Appl. Polym. Sci., 2010, 116, 308–313; (j) E. D. Pereira, D. Homper, J. Sanchez and B. Rivas, J. Chil. Chem. Soc., 2015, 60, 3054–3058; (k) R. Yang, K. B. Aubrecht, H. Ma, R. Wang, R. B. Grubbs, B. S. Hsiao and B. Chu, Polymer, 2014, 55, 1167–1176.

---

Footnote

† Electronic supplementary information (ESI) available: Synthetic details, characterization, and X-ray crystallographic data. CCDC 1477173–1477175. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra16230d

---