Science of the Total Environment 891 (2023) 164385 Contents lists available at ScienceDirect Science of the Total Environment journal homepage: www.elsevier.com/locate/scitotenv Comparative study on removal of platinum cytostatic drugs at trace level by cysteine, diethylenetriamino functionalized Si-gels and polyethyleneimine functionalized sponge: Adsorption performance and mechanisms ⁎ Dong Han a, Montserrat López-Mesas a, , Markel Luaces b, Yusleydi Enamorado b, Martina Sanadar c, Andrea Melchior c, Manuel Valiente a a GTS-UAB Research Group, Department of Chemistry, Faculty of Science, Universitat Autònoma de Barcelona, Bellaterra, (Cerdanyola del Vallès), 08193 Barcelona, Spain b Faculty of Chemistry, University of Havana, 10400 Havana, Cuba c Dipartimento Politecnico di Ingegneria e Architettura, Università di Udine, via del Cotonificio 108, 33100 Udine, Italy H I G H L I G H T S G R A P H I C A L A B S T R A C T • Adsorption of emerging contaminants Pt- cytostatics using functionalized materials • Effective elimination of trace concentra- tions of cisplatin and carboplatin • Removal of Pt-cytostatics from hospital wastewater analogs • Explanation of the adsorption mecha- nisms of different Pt compounds • Enhanced adsorption via complexation be- tween Pt-cytostatics and thiol groups A R T I C L E I N F O A B S T R A C T Editor: Damia Barcelo To efficiently remove trace Pt-based cytostatic drugs (Pt-CDs) from aqueous environments, a comparative investiga- tion was conducted on the adsorption behavior of three commercial adsorbents including cysteine-functionalized silica Keywords: gel (Si-Cys), 3-(diethylenetriamino) propyl-functionalized silica gel (Si-DETA) and open-celled cellulose MetalZorb® Platinum cytostatics sponge (Sponge). The research on the adsorption of cisplatin and carboplatin encompasses investigations of pH depen- Adsorption dence, adsorption kinetics, adsorption isotherms, and adsorption thermodynamics. The obtained results were com- Cisplatin Carboplatin pared with those of PtCl2− 4 to better understand the adsorption mechanisms. The adsorption of cisplatin and Functionalized adsorbents carboplatin by Si-Cys was significantly better than Si-DETA and Sponge, which suggested that in chelation- dominated chemisorption, thiol groups provided high-affinity sites for Pt(II) complexation. Adsorption of the anion PtCl2− 4 was more pH dependent and generally superior to that of cisplatin and carboplatin, benefiting from the contri- bution of ion association with protonated surfaces. The removal process of aqueous Pt(II) compounds occurred by the hydrolysis of complexes in solution and subsequent adsorption, and the specific adsorption process was explained by the synergistic action of ion association and chelation mechanisms. The rapid adsorption processes involving diffusion and chemisorption were well described by pseudo-second-order kinetic model. The isotherm studies suggested mono- layer adsorption, consistent with the Langmuir model. Indicated from the adsorption enthalpy results, the chelation of cisplatin and carboplatin with thiol groups was an endothermic reaction, while the adsorption of PtCl2− 4 was exother- mic. At 343 K, Si-Cys achieved 98.5 ± 0.1 % (cisplatin) and 94.1 ± 0.1 % (carboplatin) removal. To validate the ⁎ Corresponding author. E-mail addresses: Dong.Han@uab.cat (D. Han), montserrat.lopez.mesas@uab.cat (M. López-Mesas). http://dx.doi.org/10.1016/j.scitotenv.2023.164385 Received 21 March 2023; Received in revised form 16 May 2023; Accepted 20 May 2023 Available online 25 May 2023 0048-9697/© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). D. Han et al. Science of the Total Environment 891 (2023) 164385 obtained findings, the described process was applied to urine samples doped with Pt-CDs as analog of hospital waste- waters and the removal was very efficient, ranging from 72 ± 1 % to 95 ± 1 %, when using Si-Cys as adsorbent, al- though limited matrix effects were observed. 1. Introduction balance between economics, ease of operation and treatment efficiency. Moreover, adsorption demonstrates its applicability even at low concentra- Cisplatin (cis-diamminedichloroplatinum (II)) and carboplatin (1,1- tions of adsorbates, its capability in both batch and continuous processing cyclobutanedicarboxylatodiammineplatinum (II)), both well-known cyto- modes, as well as the potential for recovery and regeneration of the adsor- static agents, are administered intravenously to treat various types of can- bent (Patel et al., 2019). Several adsorbent materials have been validated cers, including sarcomas, carcinomas, and germ cell tumors (Loehrer, for their potential in the elimination of Pt-CDs (Dobrzynska et al., 2021; 1984; Prestayko et al., 1979; Zamble and Lippard, 1995). Pharmacokinetic Farías et al., 2020; Folens et al., 2018; Fraguela et al., 2023; Lenz et al., studies revealed that approximately 10–40 % of total Pt administered is ex- 2005; Ogata et al., 2014). However, most of the previous adsorption exper- creted in the urine within 24 h, in the form of intact cisplatin which ac- iments were carried out based on concentrations far higher than actual counts for the majority of Pt excreted within 1 h of administration, or concentrations found in environments. For example, the newly reported their metabolites and transformation products (Hann et al., 2003; low-cost adsorbent, Dithiocarbamate-Modified Silica (Fraguela et al., Hoffmann-La Roche, 2020; Schmidt, 2019). These Pt compounds end up 2023), has achieved the effective removal of cisplatin in physiological in hospital wastewater. Additionally, as a result of more frequent outpatient conditions, but the study is based in concentration range > 5 mg L−1. treatments, domestic discharge has become another considerable contribu- However, low Pt-CDs concentration will pose a challenge for efficient tion of excreted Pt compounds, which is directly and inevitably discharged and fast adsorption, since small concentration gradients are insufficient into municipal wastewater (Gouveia et al., 2023). Several studies, by means to drive Pt compounds at the liquid-solid interface. Secondly, the re- of advanced analytical methods, has shown the emergence of Pt-CDs in dif- ported adsorbents often require contact time of up to 24 h to reach equi- ferent water matrices (Ghafuri et al., 2018; Ghafuria et al., 2018; Isidori librium when adsorbing Pt compounds (Folens et al., 2018; Lenz et al., et al., 2016; Johnson et al., 2013; Kümmerer et al., 1999; Lenz et al., 2005; Ogata et al., 2014). The slow kinetic performance would not be 2007a; Lenz et al., 2007b; Lenz et al., 2005; Roque-Diaz et al., 2021; conducive to scaling up the adsorption system to a column adsorption Santana-Viera et al., 2020). European-wide investigations have found Pt system and landing on a field application (Farías et al., 2020; Folens compounds at concentrations ranging from tens of ng L−1 to a few hundred et al., 2018; Ogata et al., 2014). Some studies have initiated their ad- μg L−1 in hospital wastewaters (Ghafuria et al., 2018; Isidori et al., 2016; sorption investigations utilizing PtCl 2− 4 or PtCl2− 6 as a preliminary Kümmerer et al., 1999; Lenz et al., 2007a; Lenz et al., 2007b; Lenz et al., model (Dobrzynska et al., 2021; Folens et al., 2018). However, it should 2005; Santana-Viera et al., 2020; Vyas et al., 2014). Also, by analyzing sam- be noted that the adsorption mechanism of these models may differ ples from conventional wastewater treatment plants (WWTPs), it has been from that of the intended targets, and this aspect has been disregarded revealed that Pt concentration of municipal wastewater was one to three or- in said studies. For example, when adsorbents as biochar, chitosan, ders of magnitude lower than that of hospital wastewater (Ghafuri et al., and granular activated carbon were used to adsorb cisplatin, carbo- 2018; Isidori et al., 2016; Santana-Viera et al., 2020). Through extensive di- platin and oxaliplatin respectively, substantial differences from tem- lution, it appears fortuitous that the concentration of Pt in surface waters re- plate PtCl2−6 in Pt recovery were already observed by authors (Folens mains consistently negligible and typically falls below the limit of detection et al., 2018). But these differences could not be well explained in detail. (LODs), making its detection infrequent (Besse et al., 2012; Ghafuri et al., Interestingly, another material reported, Pt(II)-imprinted thiocyanato- 2018; Isidori et al., 2016; Vyas et al., 2014). Regrettably, the hazardous functionalized SBA-15 (Dobrzynska et al., 2021) showed the similar re- Pt-CDs also have the potential to damage healthy cells within living organ- moval effect as the template PtCl2− 4 when adsorbing cisplatin, carbo- isms. The ecotoxicology and environmental risks of cisplatin or carboplatin platin and oxaliplatin but with achieving equilibrium in seven days. have been assessed in recent years, and it can pose serious carcinogenic, ter- In conclusion, to address the above-mentioned issues, subsequent re- atogenic and mutagenic effects on exposed aquatic organisms (Araújo et al., search needs to focus more on the adsorbents with strong affinity and 2019; Ghafuria et al., 2018; Heath and Isidori, 2020; Jureczko and Kalka, high selectivity for Pt-CDs at trace concentrations in the environment. 2020; Li et al., 2021; Mišík et al., 2019; Queirós et al., 2021; Villarini In turn, to achieve this goal, it is essential to explore and explain possi- et al., 2016; Yadav et al., 2021). In addition, the consequences of prolonged ble different adsorption mechanisms, especially in the face of diverse low-dose exposure might be underestimated and have not been fully char- Pt-CDs. acterized. Conventional WWTPs have been shown to be insufficient to ef- This study first investigated the adsorption of cisplatin and carboplatin fectively deal with this environmental threat due to the great challenges from aqueous solutions at trace concentrations typically present in real hos- posed by the treatment of low-concentration Pt-CDs contaminated waste- pital wastewaters, using three commercially available adsorbents: cysteine- water (Abdulbur-Alfakhoury et al., 2021; Heath and Isidori, 2020; Roque- functionalized silica gel (Si-Cys), 3-(diethylenetriamino)propyl-functional- Diaz et al., 2021). ized silica gel (Si-DETA), and a derivatized open-celled MetalZorb® sponge This urgent environmental issue has raised concerns, and efforts have (Sponge). Moreover, the adsorption of PtCl2− 4 , a compound with a struc- been made to explore potentially promising laboratory-scale treatments to- tural similarity to cisplatin that has been widely utilized as a template in wards Pt-CDs contaminated wastewater (Roque-Diaz et al., 2021), including prior research, was also investigated for comparative purposes, with the dif- membrane bioreactor system (MBR) treatment (Lenz et al., 2007b), MBR ferences in its intrinsic adsorption behavior being firstly elucidated. In de- coupled with adsorption and UV-treatment (Lenz et al., 2007a), and ad- tail, the influence of several parameters including pH, contact time, initial vanced oxidation process techniques (AOPs) (Hernández et al., 2008; concentration, and temperature was studied. Hirose et al., 2005; Kobayashi et al., 2008; Pieczyńska et al., 2017). Although these disposal methods have achieved certain effects, they are often accom- 2. Experimental methods panied by some shortcomings such as prolonged treatment time require- ments, complicated installation and operation procedures, and high energy 2.1. Materials demands. Additionally, for example, after AOPs treatment, platinum by- products may still pose an environmental threat as heavy metal ions. Potassium tetrachloroplatinate (II) (K2PtCl4, 99.9 %, CAS: 10025–99- Compared with the aforementioned treatment methods, adsorption 7), diamminedichloroplatinum (II) (cisplatin, 99 %, CAS: 15663–27-1) shows certain advantages over other technologies when considering the and 1,1-cyclobutanedicarboxylatodiammineplatinum (II) (carboplatin, 2 D. Han et al. Science of the Total Environment 891 (2023) 164385 99 %, CAS: 41575–94-4) were purchased from STREM Chemicals 2.4. Adsorption kinetic and isotherm modeling and were used without further purification. K2PtCl4, cisplatin and car- boplatin stock solution (Pt concentration 100 mg L −1) was initially To further understand the Pt adsorption behavior, kinetic models in- prepared in 0.2 mol L−1 HCl respectively, and then diluted to the re- cluding pseudo-first-order model (PFOM) and pseudo-second-order model quired concentration. Cysteine-functionalized silica gel (Si-Cys) and 3- (PSOM) were used to fit the adsorption data collected at different contact (diethylenetriamino)propyl-functionalized silica gel (Si-DETA) were time, while data obtained from different initial concentration were fitted purchased from Sigma-Aldrich. MetalZorb® sponge (Sponge) was kindly with Langmuir and Freundlich isotherm models. The adsorption kinetic supplied by CleanWay Environmental Partners, Inc. (Portland, USA). and isotherm equations are described in Supplementary data. Details of the three commercial adsorbents are shown in Fig. S1(in Supple- mentary data). Milli-Q water (resistivity of 18.2 MΩ/m) was used through- 2.5. Experimental validation of the removal of Pt-CDs in wastewater analog out the entire experiment. samples 2.2. Preparation and characterization of adsorbents To validate the feasibility and efficiency of the Pt-CDs removal, experi- ments were carried out by using urine samples doped with Pt-CDs as hospi- Cube-shaped sponge (Fig. S1c, in Supplementary data) is an open-celled tal wastewater analogs. To this purpose, and due to the difficulty of cellulose sponge that incorporates a water-insoluble polyamide chelating obtaining hospital samples, hospital wastewater analogs were prepared polymer formed by the reaction of polyethyleneimine and nitrilotriacetic from anonymous urine samples obtained from a healthy male spiked with acid. The sponge was claimed to contain free available ethyleneamine cisplatin and carboplatin at the level of reported excreted in urine of pa- and iminodiacetate groups that could interact with heavy metals ions by tients undergoing chemotherapy (cisplatin concentration from ion exchange mechanism and chelation (Lou et al., 2022a; Lou et al., 312.39 μg L−1 to 114.81 mg L−1) (Jantarat et al., 2021). Then, these sam- 2022b; Muñoz et al., 2002). These cubes were ground in a knife-milling ples were diluted ten and 100-fold to account for typical conditions in hos- commercial blender and sieved to a particle size of ≤0.5 mm. These fine pital wastewaters. Ion chromatography (Dionex Aquion, Thermo Scientific, sponge powders were washed with 1.0 mol L−1 HCl and Milli-Q water sev- America) was employed to determine the concentration of typical anions eral times. Then the Sponge was dried at 80 °C for 24 h and stored for fur- and cations in urine and two wastewater analogs, and details are described ther studies. in Supplementary data. Experiments were carried out by contacting the pre- To identify the functional groups of Si-Cys, Si-DETA, and Sponge, Fou- pared analog samples with the adsorbent Si-Cys in the same conditions as rier Transform Infrared Spectroscopy equipped with an Attenuated Total explained when using the synthetic Pt-CDs solutions. Thus, 10 mL of the re- Reflectance module (ATR-FTIR, Tensor 27, Bruker, Germany) was used to sulting Pt-spiked urine samples were then respectively mixed with 50 mg of record the FTIR spectra. The total content of C, H, N and S of three adsor- the selected adsorbent (stirred for 24 h, T = 343 K, pH 2) and were col- bents was determined using element analyzer (Flash EA 2000 CHNS, lected using sterile plastic bottles after filtration using 0.22 μm filters. The Thermo Fisher, America). Brunauer-Emmett-Teller (BET) analysis results samples were immediately quantified using a standard analytical method of Si-Cys and Si-DETA were provided by the manufacturer. described elsewhere (Flores et al., 2011; Gao et al., 2012). In our case, an- alog samples aliquots (100 μL) were equilibrated to room temperature 2.3. Batch adsorption and digested using 200 μL of nitric acid (69.0–70.0 %, for trace metal anal- ysis) at 363 K for 1 h. The digested samples were then diluted to 10 mL with The adsorption of PtCl2− 4 , cisplatin and carboplatin was studied as a Milli-Q water to a final concentration of 2 % v/v HNO3. These solutions function of pH (pH 2–6, controlled by 0.1 mol L−1 HCl and/or were instantly subjected to ICP-MS analysis with external calibration rang- 0.1 mol L−1 NaOH before, during, and after the adsorption, and monitored ing from 1 to 150 μg L−1 (Rh and Y as internal standard elements). The cal- by pH meter, Crison, Spain), contact time (1–180 min), initial concentra- culation of removal ratio was according to Eq. (2). tion (47 μg L−1 -1000 mg L−1, all concentrations of Pt compounds are expressed as Pt), and solution temperature (293, 318 and 343 K). A series 3. Results and discussion of batch adsorption experiments were performed in 10 mL plastic centri- fuge tubes containing 10 mL of Pt solution (in form of PtCl2−4 , cisplatin or 3.1. Characterization of adsorbents carboplatin). After 50 mg of adsorbent was added, the tubes were agitated mechanically at 300 rpm at 293 K (except for thermodynamic studies). The FTIR test was performed on Si-Cys, Si-DETA, and Sponge, showing After 24 h (except for kinetic studies), the adsorbent in solution was the spectra observed in Fig. 1. The spectra of Si-Cys and Si-DETA are very filtrated using a 0.22 μm filter. The concentration of Pt in solutions was de- similar, and the characteristic peaks mainly correspond to the properties termined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS, of silica. Absorption bands at 1051 cm−1 and 795 cm−1 arise from Thermo XSeries II, Thermo Scientific, USA). asymmetric vibration of Si-O-Si and symmetric vibration of Si-O-Si, respec- The adsorption capacity qe (μg g−1) of Pt at equilibrium was calculated tively (Grumezescu et al., 2014). The peaks at 2973 cm−1 and 2900 cm−1 by the Eq. (1): represent the C\\H stretching vibration of the alkyl groups. The broad band at around 3273 cm−1 was assigned to N\\H stretching of amine, which was ðc0  ce Þ relatively weak due to low load rate of cysteine and 3-(diethylenetriamino) qe ¼ V (1) m propyl groups. Then, the band appears at 1615 cm−1 for Si-Cys represent- ing C_O stretching vibration. For Sponge, the absorbances at 3435, where c0 and ce (μg L−1) are the initial and equilibrium concentrations of Pt 2891, 1365, 1157, and 1024 cm−1 are associated with cellulose substrate solutions, respectively. V (mL) is the volume of solution and m (mg) is the (Li et al., 2009). A strong band 3435 cm−1 originates from the O\\H adsorbent dosage. For kinetic studies, the concentration at equilibrium is stretching. The peak at 2891 cm−1 is attributed to the stretching vibration replaced by the concentration at different contact time, ct (μg L−1), calculat- of alkane C\\H. The absorption at 1365 cm−1 is due to O\\H bending and ing the adsorption capacity qt (μg g−1). that at 1157 cm−1 corresponds to C-O-C antisymmetric bridge stretching. Then the removal ratios were calculated according to Eq. (2): The strong peak at 1024 cm−1 can be assigned to C-O-C pyranose ring skel- etal vibration. Besides, the surface polyamide chelating polymer contrib- ðc0  ce Þ Removal ratio ¼  100% (2) utes to the strong band at around 3317 cm−1 due to the N\\H stretching. c0 The peak at 1637 cm−1 is related to the C_O stretching vibration and All the experiments were conducted in triplicated, and the average the rightward shift of the peak coincides with the amide structure (elec- values and the relative standard deviation were calculated. tron-donating property of nitrogen). These findings are consistent with 3 D. Han et al. Science of the Total Environment 891 (2023) 164385 (H2O)− molecules were repelled, as a result, there was a significant de- crease in the adsorption capacity. Meanwhile, however, the changing of ad- sorption capacity with increasing pH was moderated when Si-DETA was studied, adsorption capacity of Si-DETA dropped slightly from 48 ± 1 to 42 ± 1 μg g−1 in the same range of pH. The elevation of pH levels induced deprotonation of amine groups in Si-DETA, resulting in a reduction of its positive charge density. As a consequence, the effectiveness of electrostatic attraction-assisted adsorption was moderately diminished. The effect of pH on the adsorption of PtCl2− 4 to Sponge is almost negligible. For cisplatin (Fig. 2b) and carboplatin (Fig. 2c), the adsorption capaci- ties were overall lower than that of PtCl2− 4 and slightly affected by pH changes, since facing cisplatin and carboplatin (neutral molecules) as well as their hydrated complexes (non-anionic molecules) electrostatic attraction did not contribute to the adsorption. Regarding the adsorbents, Si-Cys has higher adsorption capacities of cisplatin and carboplatin than Si-DETA and Sponge due to the presence of thiol groups in Si-Cys. Accord- ing to HSAB theory (Bugarčić et al., 2012), Pt(II) as a “soft” acid has a high affinity for sulfur donors (“soft” bases) e.g. thiols and thioethers. For exam- ple, it is assumed that most of Pt-CDs bind to glutathione and L-cysteine in intracellular liquid forming stable compounds before it reaches DNA (Bugarčić et al., 2012; Reedijk, 2009; Reedijk, 1999). This suggests that in chelation-dominated chemisorption (Fig. 3b and c), thiol groups provide more chelation sites for the complexation of cisplatin and carboplatin. In addition, it is worth mentioning here that the influence of the alkaline Fig. 1. FTIR spectra of Si-Cys, Si-DETA, and Sponge. environment is not considered, because the chemical structures of PtCl2− 4 , cisplatin and carboplatin are not stable when the pH exceeds 6. Black pre- the interpretation of the chemical structure of the different adsorbents, cipitation appeared in both stocks prepared by directly dissolving com- shown in Fig. S1(in Supplementary data). pounds in water at pH > 6, due to the oxidation of Pt. BET analysis and elemental analysis (EA) results are summarized in Table S1 and Table S2 (in Supplementary data), respectively. The EA anal- 3.2.2. Adsorption kinetics analysis ysis conducted confirmed the existence of the respective functional groups Kinetic is an important index to evaluate the removal efficiency and in the three adsorbents, which aligns with the FTIR findings and uphold the mechanism of the adsorption process, that is a key knowledge to scale up claims made by the manufacturers. the Pt-CDs removal to industrial application. Fig. 4A and a give the adsorp- tion kinetic curves of PtCl2− 4 onto Si-Cys, Si-DETA, and Sponge. It is shown 3.2. Adsorption experiments a fast adsorption kinetics for all the three materials. The adsorption capac- ities rose sharply within the first few minutes, because there are rich effec- 3.2.1. Effect of solution pH on adsorption tive adsorption sites on the surface of Si-Cys, Si-DETA, and Sponge at the The pH is one of the key factors that determine the interaction between beginning of the adsorption process. Then the growth gradually slowed adsorbate and adsorbent as it can change the protonation state of surface down until reaching the adsorption equilibrium after approximately functional groups, thereby changing the surface charge, which in turn af- 40 min, as the amounts of available active sites gradually decreased, lead- fects the adsorption performance. For adsorption of PtCl2− 4 (Fig. 2a), the ing to a decrease in the adsorption rate. However, despite of the fast kinet- pH dependences of the three materials are very different. The adsorption ics, the adsorption of cisplatin and carboplatin still exhibited disadvantages capacity of Si-Cys decreased considerably from 45 ± 1 to 19 ± 4 μg g−1 if compared to that of PtCl2−4 (see in Fig. 4). The removal rate of Si-DETA as pH increased from 2 to 6. As implied in Fig. 3a, after dilution from Pt and Sponge for cisplatin was only 32 ± 2 % and 38 ± 3 % (while 9 ± stock (in 0.2 mol L−1 HCl), the Cl ligands are gradually displaced by H2O 1 % and 10 ± 2 % for carboplatin), compared to 90 ± 1 % and 83 ± to give the aqua complexes (like PtCl3(H2O)−). And at low pH values, the 3 % for PtCl2−4 . This confirmed the inference in the previous section that amino groups were protonated, which made the adsorbent to be positively the adsorption was frustrated due to the lack of thiol groups to provide com- charged. The protonation facilitated Si-Cys to attract anionic PtCl2− 4 and/or plexation sites. In addition, carboplatin showed worse adsorption perfor- PtCl3(H2O)− through ion association, concomitantly, Pt gradually chelated mance, which was caused by its low hydrolysis rate. Meanwhile, the with the S sites and the N sites (even with low affinity). However, when the removal rate of Si-Cys also slightly decreased from 92 ± 1 % for PtCl2− 4 pH kept increasing, the carboxyl group, thiol group and protonated amine to 74 ± 1 % for cisplatin and 73 ± 1 % for carboplatin, indicating that elec- group sequentially deprotonated, which eventually caused Si-Cys to be neg- trostatic adsorption probably did not play a role in adsorbing cisplatin and atively charged. Due to electrostatic repulsion, parts of PtCl2− 4 and/or PtCl3 carboplatin molecules. qe Fig. 2. The effect of solution pH on the adsorption capacity of (a) PtCl2− 4 , (b) cisplatin and (c) carboplatin [adsorbent dosage: 50 mg, solution volume: 10 mL, Pt concentration: 235 μg L−1, T: 293 K]. 4 D. Han et al. Science of the Total Environment 891 (2023) 164385 Fig. 3. The difference in adsorption mechanism between (a) PtCl2− 4 , ion association enhanced adsorption to amino-rich adsorbent surface (adsorption to Si-Cys containing thiol group is omitted here); (b) cisplatin and (c) carboplatin chelation dominant adsorption to thiol-containing Si-Cys surface. The kinetics fitting curves are also plotted in Fig. 4. As indicated by the reaches equilibrium. Adsorption capacities mounted with the increase of correlation coefficients R2 summarized in Table S3 (in Supplementary the initial concentration of PtCl2− 4 , cisplatin and carboplatin solution (see data), PSOM fitted better than PFOM. As is known PSOM assumes that in Fig. 5), which may be due to the higher concentration gradient at the the rate-limiting step may be chemisorption involving valance forces solid-liquid interface. The mass transfer of PtCl2− 4 , cisplatin and carboplatin through sharing or exchanging electrons between adsorbate and adsorbent towards the surface of adsorbents could be driven by the concentration gra- (Feiqiang et al., 2018; Mohan et al., 2011; Sen Gupta and Bhattacharyya, dient, which satisfied the generalized Fick Law (Chinh et al., 2019; Han 2011). Specifically, this is consistent with the ion-association between the et al., 2021). It can be seen from Fig. 5A that the maximum adsorption ca- PtCl2− 4 anion and the protonated amine group, and the complexation be- pacity of Si-DETA (169 ± 6 mg g−1) to PtCl2− 4 is greater than that of Si-Cys tween Pt and surface functional groups such as thiol, amino and carboxyl (131 ± 1 mg g−1), due to the different loading rates of their respective groups. Furthermore, it has been reported that the PFOM is more suitable functional groups, -Cys (0.3 mmol g−1) and -DETA (1.3 mmol g−1) (pro- for the description of the initial stage in which the external/internal diffu- vided by the manufacturer, see Fig. S1a and S1b, in Supplementary data). sion is the rate controlling step, and the initial concentration of adsorbate Moreover, the adsorption of PtCl2− 4 surpasses that of the other two Pt com- is usually high (Feiqiang et al., 2018; Wang and Guo, 2020a). However, pounds, ascribed to the complementary effect of electrostatic adsorption the initial concentration of the target Pt compounds here was as low as and Van der Waals force, alongside the presence of ligands (Cl) that readily 235 μg L−1, and the adsorbents are abundant with active sites, therefore, detach from the molecule. Cisplatin and carboplatin contain two inert NH3 the adsorption kinetics are dominated by the adsorption onto active site ligands which makes complexation to the adsorbent surface more difficult. as PSOM expected. This predicament is slightly alleviated when Si-Cys containing thiol func- tional groups were used to adsorb cisplatin and carboplatin. 3.2.3. Adsorption isotherms analysis The isotherm fitting curves are also plotted in Fig. 5, and parameters de- Adsorption isotherm reveals the relationship between the adsorbate rived from models are summarized in Table S4 (in Supplementary data). concentration in the liquid and solid phases when the adsorption process Langmuir model represents satisfactorily the adsorption process with high 5 D. Han et al. Science of the Total Environment 891 (2023) 164385 qt qt Fig. 4. The effect of contact time on the adsorption capacity of (A) PtCl2− 4 , (B) cisplatin and (C) carboplatin [adsorbent dosage: 50 mg, solution volume: 10 mL, Solution pH = 2 for Si-Cys and Si-DETA, solution pH = 3 for Sponge, Pt concentration: 235 μg L−1, T: 293 K] and kinetic models fitting. The lowercase figures (gray background) are the enlarged interval (0–40 min). coefficients of determination (R2 > 0.92) and gives a better fit than better). The results indicate that the adsorption of three Pt compounds by Freundlich model only except for Si-Cys adsorption of cisplatin and Si- all adsorbents takes place in a monolayer adsorption manner. In addition, DETA adsorption of carboplatin (while Freundlich model fit is slightly the adsorption (Fig. 5a-c) in the low concentration range obeys the linear qe ce ce ce qe ce ce ce Fig. 5. Adsorption equilibriums of (A) PtCl2− 4 , (B) cisplatin and (C) carboplatin [adsorbent dosage: 50 mg; solution volume: 10 mL; initial concentration: maximum 1000 mg L−1 of PtCl2−4 and carboplatin, 500 mg L −1 of cisplatin because of low solubility; solution pH = 2 for Si-Cys and Si-DETA, solution pH = 3 for Sponge; contact time 24 h; T: 293 K] and isotherm models fitting. The lowercase figures (gray background) are the enlarged interval (initial concentration 47–14,100 μg L−1). 6 D. Han et al. Science of the Total Environment 891 (2023) 164385 model (Henry's law), which also illustrates the monolayer adsorption be- neutral cisplatin or carboplatin, and the complexation of Pt\\N was havior with low coverage (Wang and Guo, 2020b). From the data listed weaker), they also showed a trend of increasing and then decreasing during in Table S4 (in Supplementary data), all the Langmuir separation factor the warming process (see in Fig. 6B,C and 6b,c). For instance, when the RL fell into 0 to 1 within the concentration range investigated. It proves temperature increased from 293 K to 318 K, adsorption capacities of cis- that all Pt adsorptions towards three materials are favorable. The theoreti- platin on Si-DETA and Sponge generally increased (except for the adsorp- cal maximum adsorption qm predicted by the Langmuir model is close to tion of Si-DETA in Fig. 6b, which adsorption decreased by a very small but slightly higher than the actual maximum adsorption capacity obtained amount of 1.66 μg L−1), which was due to the high temperature promoting in the experiment. Regarding the Freundlich constant, all adsorption pro- to some extent the complexation of Pt with the amine functional groups on cesses are favorable as the value of 1/n < 1. the surface of Si-DETA and Sponge. However, as explained before, this com- plexation was very limited because of the fact that N is a “hard” base and its 3.2.4. Thermodynamics of adsorption processes bonding with the “soft” acid Pt is not favored. Therefore, when the temper- Experimental thermodynamic analysis was performed under different ature continued to increase up to 343 K, the decline brought by the frus- temperatures to further understand the adsorption behavior. For PtCl2− 4 trated Van der Waals adsorption came to the fore. (see in Fig. 6A), with the increase of adsorption temperature (from 293 to Furthermore, three thermodynamic parameters including Gibbs free en- 343 K), the adsorption capacities of Si-Cys, Si-DETA, and Sponge all de- ergy (ΔG°), enthalpy change (ΔH°), and entropy change (ΔS°) were calcu- creased slightly. Then when initial concentrations doubled to 470 μg L−1, lated by equations described in Supplementary data. Results are listed in the decline was more obvious (see in Fig. 6a). As illustrated in Fig. 3a, the Table S5 (also in Supplementary data). adsorption of anionic PtCl2− 4 was dominated by physical adsorption such As seen in Table S5, PtCl2−4 adsorption is a spontaneous process with as electrostatic attraction and Van der Waals forces. Specifically, the weak negative ΔG°. It can be seen from the comparison of ΔH° that the adsorption binding between PtCl2− 4 and adsorbents surface caused by Van der Waals of PtCl2− 4 by Si-Cys was very different from that of cisplatin or carboplatin. interactions, which are always present in adsorption processes (Veclani First, as can be determined from the positive value of ΔH°, the adsorption of et al., 2020), were easily undermined as the solutions were heated up to cisplatin or carboplatin is endothermic reaction (while that of PtCl2− 4 is exo- 343 K. In comparison, the adsorption of cisplatin is much more compli- thermic). Additionally, cisplatin has an enthalpy value (ΔH° = 44 ± cated. As shown in Fig. 6B and b, the adsorption capacities of Si-Cys to cis- 7 kJ mol−1) approximately twice as high as the ΔH° of PtCl2− 4 (ΔH° = platin were greatly promoted when temperature was increased, and the −23 ± 6 kJ mol−1), which corroborates the dominance of chemisorption removal rates almost reached the theoretical maximum at 343 K (98.5 ± in the adsorption of cisplatin by Si-Cys. It can be recognized that tempera- 0.1 % and 97.5 ± 0.5 % for initial concentration of 235 and 470 μg L−1, ture promoted bonding of Pt\\S, and enthalpy change of this process was respectively). The adsorption process of carboplatin also showed a similar incontrovertibly higher than that involved in physisorption. In addition, pattern. This implied that the chemisorption dominated by chelation was the entropy changes of Si-Cys in the process of adsorbing PtCl2− 4 and a thermophilic process, and the complexation between Pt and S from the other two Pt-CDs are also diametrically opposite. Negative values of ΔS° in- thiol group was facilitated at higher temperatures during the process. dicated an increase in the order of the system during the adsorption process However, for the other two adsorbents, Si-DETA and Sponge, the adsorp- 4 at solid-liquid interface, while positive ΔS° suggested an increase of PtCl2− tion capacities of them for cisplatin and carboplatin were not only much of the degrees of freedom when cisplatin and carboplatin was adsorbed on lower than that of Si-Cys (electrostatic adsorption was ineffective for Si-Cys. qeqe −1 4 , Pt concentration: (A) 235 μg L Fig. 6. The effect of temperature on the adsorption capacity of PtCl2− and (a) 470 μg L−1; cisplatin, Pt concentration: (B) 235 μg L−1 and (b) 470 μg L−1; carboplatin, Pt concentration: (C) 235 μg L−1 and (c) 470 μg L−1. [adsorbent dosage: 50 mg, solution volume: 10 mL, contact time: 24 h, Solution pH = 2 for Si-Cys and Si-DETA, solution pH = 3 for Sponge]. 7 D. Han et al. Science of the Total Environment 891 (2023) 164385 3.3. Experimental validation of the removal of Pt-CDs in wastewater analog in urine posed additional competition for active binding therefore slightly samples inhibited the capture of cisplatin and carboplatin (Curtis et al., 2010). For the undiluted samples, the Pt species had more competitive advantages The results of the removal of Pt-CDs in wastewater analog samples are when the initial concentration was increased to 57 or 115 mg L−1, hence depicted in Fig. 7, and the characteristics of urine and wastewater analogs the removal rates increased significantly driven by the high concentration are summarized in Table S6 (in Supplementary data). It can be observed gradients. The interference from matrix effects diminished gradually with by comparing Fig. 7a and b, the Si-Cys adsorption towards the two targets more dilution of urine, almost all removals reached the maximum (92 ± generally achieved similar removal rates, which are from 72 ± 1 % to 1 % - 95 ± 1 %) when adsorptions were carried out in 100-fold diluted 95 ± 1 % for cisplatin and from 75 ± 1 % to 95 ± 1 % for carboplatin. urine samples. The only exception occurred in the adsorption of spiked The removal was found to be less efficient for low concentrations of cis- low-concentration Pt from urine. When the urine samples were further di- platin and carboplatin in undiluted urine samples, likely due to the com- luted from ten times to 100 times, the removal rate decreased unexpect- plexity of the urine matrix (as Table S6 shows). Furthermore, the edly. However, the initial Pt concentration was as low as only observed removal of Pt-CDs in simulated wastewaters was consistently 3.12 μg L−1, which may predict the ineffective capture of Pt molecules at lower than that in Milli-Q water. This disparity may be attributed to the ma- such a low concentration. Perhaps longer time or higher temperature can trix effect that arises from the presence of urine and tap water. One of its in- guarantee more Pt\\S complexation formed for ideal adsorption. terferences may be derived from the trace protein contained in urine such Then when the mixture of cisplatin and carboplatin was adsorbed from as Tamm-Horsfall protein (Aitekenov et al., 2021; Micanovic et al., 2020), 100-fold diluted urine, as shown in Fig. 7c, around 95 % of Pt was effec- which contains cystines sites that pre-chelated part of cisplatin and carbo- tively removed. The removal of Pt-CDs from 100-fold diluted urine is com- platin. Secondly, the ligands replacement of cisplatin and carboplatin parable to that from Milli-Q water, albeit slightly lower. could be disturbed due to the presence of components such as Cl− and NH+ 4 in urine matrix, which were significantly more abundant than Pt- 3.4. Comparison of the adsorption performance with current knowledge CDs as indicated in the Table S6, thus the complexation of Pt to the Si-Cys surface was also affected (Guo et al., 2020). In addition, co-existing ions The adsorption efficiency of Si-Cys for cisplatin and carboplatin was such as Na+, K+, Ca2+ and so on (several to thousands of mg L−1) present compared with other published adsorbents and listed in Table 1. It is Fig. 7. Removal of (a) cisplatin and (b) carboplatin from spiked urine samples, its ten-fold diluted and 100-fold diluted matrices; (c) mixture of cisplatin and carboplatin from 100-fold diluted urine. 8 D. Han et al. Science of the Total Environment 891 (2023) 164385 Table 1 Comparison of Pt-CDs removal by Si-Cys to adsorbents previously reported. Adsorbent Target Pt compound Contact time (h) Dosage (g L−1) Treatment effect Ref. Si-Cys Cisplatin (235 μg L−1 Pt) 40 min 5.0 98.5 ± 0.1 % removal This study Carboplatin (235 μg L−1 Pt) 94.1 ± 0.1 % removal Activated sludge Cisplatin (6.5 μg L−1 Pt) 24 4.2 96 % removal (Lenz et al., 2005) Carboplatin (5.3 μg L−1 Pt) 70 % removal Oxaliplatin (4.9 μg L−1 Pt) 74 % removal −1 Biomass-derived adsorbents (chitosan, PtCl2− 6 as model (1–10 mg L Pt) 24 10.0 Adsorption capacity 0.23–0.97 mg g−1 (Folens et al., 2018) biochar, wood ash, activated carbon) Calcination of gibbsite Cisplatin (10 mg L−1 Pt) 24 6.0 Adsorption capacity 1.5 mg g−1 (Ogata et al., 2014) Macroporous cryogels (by polymerization Cisplatin (250–2000 mg L−1) 1–48 0.5 & 2.0 Adsorption capacity up to 150 mg g−1 (Farías et al., 2020) of methacrylic acid and 2-hydroxyethyl methacrylate) −1 Pt (II)-imprinted thiocyanato-functionalized PtCl2− 4 as model (100 mg L Pt) 5 5.0 Adsorption capacity 76.4 mg g−1 (Dobrzynska et al., SBA-15 materials 2021) Dithiocarbamate-Modified Silica Cisplatin (10 mg L-1-) 0.25–2 1–10 Adsorption capacity 15.6 mg g−1 with (Fraguela et al., 1 mg mL−1. Removal up to 85 % with 2023) 10 mg L−1. 1 h contact time evident that Si-Cys achieved maximum removal of 98.5 ± 0.1 % and 94.1 ± López-Mesas: Conceptualization, Methodology, Resources, Writing – re- 0.1 % for cisplatin and carboplatin, respectively. Moreover, it was achieved view & editing, Supervision, Project administration. Markel Luaces: Vali- at a low concentration of 235 μg L−1, which is close to the environmental dation, Investigation, Writing – review & editing. Yusleydi Enamorado: concentrations. Although activated sludge (Lenz et al., 2005) also exhibited Validation, Investigation, Writing – review & editing. Martina Sanadar: good removal efficiency at low concentrations, the disadvantage of slow ki- Methodology, Resources, Writing – review & editing. Andrea Melchior: netics required a long processing time of up to 24 h. While it is acknowledged Conceptualization, Methodology, Resources, Supervision, Writing – review that novel adsorbents like macroporous cryogels (Farías et al., 2020) and Pt & editing. Manuel Valiente: Conceptualization, Methodology, Resources, (II)-imprinted thiocyanato-functionalized SBA-15 (Dobrzynska et al., 2021) Project administration, Supervision, Funding acquisition. demonstrated outstanding adsorption capacity, their adsorption was per- formed at concentrations far higher than the actual environmental concen- Data availability trations, and their removal efficiency for trace Pt-CDs remains unknown. Data will be made available on request. 4. Conclusions Declaration of competing interest This study presents a comparative investigation of the adsorption be- havior of trace cisplatin, carboplatin, and PtCl2− 4 onto three different adsor- The authors declare that they have no known competing financial inter- bents, including studies on pH effect, adsorption kinetics, adsorption ests or personal relationships that could have appeared to influence the isotherms, and thermodynamic studies. Distinct adsorption mechanisms work reported in this paper. of each Pt compounds were revealed. The major findings of this study can be summarized as follows: (1) All three adsorbents exhibited a significant Acknowledgements removal of anionic PtCl2− 4 (>90 %) compared to cisplatin and carboplatin due to the assistance of electrostatic adsorption, however, the adsorption This work has been developed in the framework of the European of PtCl2− 4 is more pH dependent. Therefore, PtCl2− 4 should be cautiously Community's H2020 Program H2020-MSCA-RISE 2017 under the project considered as a template for Pt-CDs, despite of structural similarity. RECOPHARMA (grant agreement #778266). D. Han acknowledges COST (2) Si-Cys, containing thiol groups, exhibited a remarkable removal effi- action 18202, “Network for Equilibria and Chemical Thermodynamics ciency of cisplatin (maximum 76 ± 1 %), which is significantly higher Advanced Research” (NECTAR) for supporting a STSM in Udine and the than that of Si-DETA (maximum 34 ± 1 %) and Sponge (maximum program of China Scholarships Council (No. 201906450024). The authors 40 ± 5 %). And this similar contrast was also shown in the adsorption of would also like to thank Júlia Senyé Lacher, Tania Farías, Ana Rosa Lazo carboplatin. It indicates the adsorption of cisplatin and carboplatin highly Fraga and Raquel Cantero Rodriguez for supporting in the experiment. depends on the complexation with high-affinity thiol sites. (3) All the ob- Open Access funding provided thanks to the agreement CRUE- served adsorption processes conform to the PSOM and Langmuir model de- CSIC with Elsevier. scriptions, indicative of a monolayer chemisorption process. (4) The adsorption of cisplatin and carboplatin onto Si-Cys is an endothermic pro- Appendix A. Supplementary data cess (different from exothermic adsorption of PtCl2− 4 ), as Pt\\S binding is thermally favored. As a result, the removal of cisplatin and carboplatin Supplementary data to this article can be found online at https://doi. onto Si-Cys reached 98.5 ± 0.1 % and 94.1 ± 0.1 %, respectively, when in- org/10.1016/j.scitotenv.2023.164385. creasing the temperature up to 343 K. (5) The finding of treatment of Pt- spiked urine found that thiol-containing Si-Cys can be used to treat cisplatin References and/or carboplatin-contained patient urine and hospital wastewater con- taminated by it. 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