Hydrolysis Half-life Research Articles

Dissimilar ferric derisomaltose formulations – In vitro comparisons between an originator and its intended similars

BackgroundThe complex nature of intravenous (IV) iron formulations makes manufacturing and characterising similars challenging. This study examined whether simple in vitro tests can distinguish the high-dose IV iron formulation, Monofer® (ferric derisomaltose [FDI]), from the first intended copies of FDI, Rapifer® (FDI intended similar A [FDIIS-A]) and Tosiron® (FDI intended similar B [FDIIS-B]), approved in India and Pakistan, respectively. Neither intended similar is available in Europe or the United States. MethodsIron content, pH, density, non-volatile residue, carbohydrate content, molecular weight distribution, complex robustness (measured using acid hydrolysis half-life [t½]) and free (dialysable) iron content were examined. Mean results from three batches of FDIIS-A were compared with mean values calculated from three batches of Monofer®. Due to product withdrawal, only one batch of FDIIS-B was available for comparison with Monofer®. ResultsIron content was similar for all formulations (∼100 mg/mL). The chromatograms (obtained using gel permeation chromatography) of FDIIS-A and FDIIS-B differed from that of Monofer®. FDIIS-A was substantially less robust than Monofer® (t½: 15 h versus 40.3 h); t½ for FDIIS-B was not tested. Free iron content was substantially higher in FDIIS-A (0.091 % w/v) and FDIIS-B (1.0 % w/v) versus Monofer® (<0.003 % w/v). Where tested, remaining parameters varied between the formulations (insufficient sample quantities prevented all tests being conducted for all intended similars). For all tests, greater inter-batch variability was seen for FDIIS-A versus Monofer®. ConclusionsSimple in vitro tests demonstrated that, aside from total iron content, the first intended similars of FDI bear little resemblance to their originator drug. It is clear that the efficacy and safety profile of Monofer® cannot be extrapolated to the two intended similars. The results call for increased regulatory scrutiny of intended IV iron similars.

A MOF-doped molecularly imprinted polymer/MOF hybrid gel incorporating with pH-buffering sodium acrylate for practical detoxification of organophosphorus nerve agents

The fatal toxicity of organophosphorus nerve agents (ONAs) and the realistic condition of chemical attack occurring place trigger the urgent need to develop catalyst materials with degrading ability under the natural environment without bulk water and bases. Here, we strategically design a molecularly imprinted polymer (MIP)/MOF hybrid catalyst material by integrating enzyme-mimic MIP with Zr-MOF UiO-66-NH2 which demonstrate promising catalytic performance for degradation of ONAs. Furthermore, sodium acrylate functions as a hydrophilic and alkaline functional unit together with pyridine-amidoxime based functional monomers (PAAO) to copolymerize into molecularly imprinted polymeric network. The basic sodium carboxylate groups were installed near the active sites to provide appropriate alkaline microenvironment, non-bulk water and acid buffer capacity for the catalysis in pure water. The resultant MIP/MOF composite catalyst demonstrate outstanding catalytic activities in both liquid and solid phase hydrolysis of ONAs. Specifically, the half-life of liquid phase hydrolysis catalyzed by MIP/UiO-66-NH2-0.5 achieves 9.4 min for diethyl-4-nitrophenyl phosphate (DENP) and 10 min for dimethyl 4-nitrophenyl phosphate (DMNP), and solid-state hydrolysis present rapid degradation efficiency with a half-life of 28.6 min. In addition, composite catalyst MIP-Ag/UiO-66-NH2-0.5 that retains substrate selectivity of MIP, enables the simultaneous degradation of two types of organophosphorus substrates (phosphate and thiophosphate) by MIP and MOF in a synergistic way. Summarily, this work displays promising potential of MIP/MOF hybrid enzyme-like catalyst as effective and practical material for the practical protection and detoxification of organophosphorus nerve agents.

Hydrolytic Behavior of Novel Pesticide Broflanilide and Its Dissipative Properties in Different Types of Soils.

All pesticides are toxic by nature and pose short- or long-term safety risks to human or the environment, especially when they were used extensively and absence of safety measures. As a new insecticidal active compound with a novel mechanism of action, there is a serious inadequate of information on the hydrolytic behavior of broflanilide in the aqueous environment, as well as its degradation pattern in agricultural soils. In particular, the effects of temperature and pH of the aqueous environment on its hydrolytic behaviors and the dissipation pattern in different types of agricultural soils were still in a dark box. And the further understanding and insights into this insecticidal active ingredient were being deeply conditioned by these doubts. The hydrolysis behavior of broflanilide and the dissipation pattern in soil were systematically investigated by constructing hydrolysis systems with different temperatures and pH values, and conducting spiking experiments in different types of agricultural soil in the laboratory. The obtained results showed that the longest hydrolysis half-life of 10mg/L broflanilide at 25°C was 43.32h (in pH 4.0 buffer), while it was only 12.84h in pH 9.0 buffer. In pH 7.0 buffer, the hydrolysis rate of broflanilide exhibited a significant temperature dependence, as shown by the fact that for every 10°C increase in the system temperature, the corresponding hydrolysis rate will increase about 1.5 times. The dissipation experiments in soils showed that broflanilide was most rapidly dissipated in fluvo-aquic soil (half-life of 1.94days), followed by lime concretion black soil (half-life of 2.53days) and cinnamon soil (half-life of 3.11days), and slower in paddy soil (half-life of 4.03days). It was indicated that broflanilide was a readily degradable pesticide in both aqueous environment and agricultural soil, and it was significantly affected by the temperature and pH of the system.

Dry-to-wet fluctuation of moisture contents enhanced the mineralization of chloramphenicol antibiotic

Due to livestock wastewater irrigation, soil is becoming one of the major sinks of antibiotics in the environment. Recently, it is getting recognized that a variety of minerals under low moisture conditions can induce strong catalytic hydrolysis to antibiotics. However, the relative importance and implication of soil water content (WC) for natural attenuation of soil residual antibiotics has not been well recognized. In order to explore the optimal moisture levels and the key soil properties dominating for the high catalytic hydrolysis activities of soils, this study collected 16 representative soil samples across China, and assessed their performances to degrade chloramphenicol (CAP) under different moisture levels. The results showed that the soils with low organic matter contents (< 20 g/kg) and high amounts of crystalline Fe/Al were particularly effective in catalyzing CAP hydrolysis when exposed to low WC (< 6%, wt/wt), leading to CAP hydrolysis half-lives of <40 d Higher WC greatly suppressed the catalytic activity of the soil. By utilizing this process, it is possible to integrate abiotic and biotic degradation to enhance the mineralization of CAP, attributing to that the hydrolytic products are more available for soil microorganisms. As expected, the soils experienced periodic dry-to-wet moisture conditions (i.e., the WC shifting from 1 to 5% to 20–35%, wt/wt) exhibited higher degradation and mineralization of 14C-CAP, in comparison with the constant wet treatment. Meanwhile, the bacterial community composition and the specific genera showed that the dry-to-wet fluctuation of soil WC relieved the antimicrobial stress to bacterial community. Our study verifies the critical role of soil WC in mediating the natural attenuation of antibiotics, and guides to remove antibiotics from both wastewater and soil.

A new method to treat fumigant pesticides-spent granular activated carbon utilizing alkaline hydrolysis

Groundwater treatment of recalcitrant fumigant pesticides (1,2-dibromo-3-chloropropane (DBCP), 1,2-dibromoethane (EDB), 1,2-dichloropropane (DCP), and 1,2,3-trichloropropane (TCP)) often involves a pump and treat system with granular activated carbon (GAC). A novel and promising method of treating the pesticide-spent GAC is based on alkaline hydrolysis, a well-understood abiotic transformation mechanism, that offers a potentially greener approach to conventional thermal regeneration. Here, alkaline hydrolysis of these pesticide chemicals was evaluated under homogeneous (aqueous), and heterogeneous (pesticide spent-GAC) conditions involving bituminous- and coconut-based GAC. Aqueous treatment occurred at elevated pH (pH 12.0–12.4) and the pesticide rate of hydrolysis transformation was first-order (DBCP ≫ TCP ≫ EDB ≫ DCP). Significant pesticide loss (94.95–99.98%) was achieved in both types of GAC (pH 12.0–12.4; 30 d). GAC suspensions held (5 d) at pH 11.0, 12.0, and 12.6, resulted in the DBCP loss of 74%, 89%, and 99%, respectively. The pH dependency of DBCP hydrolysis underscores the correlation between alkaline conditions, aggressive hydrolysis treatment, and reaction time for engineered systems. The estimated time (4–8 min) for full OH- intraparticle diffusion into the GAC from bulk solution was much less than the pesticide hydrolysis half-lives indicating that alkaline hydrolysis treatment of pesticides in GAC was reaction rate limited. Rapid small scale column tests demonstrated that the post-treatment (i.e., base hydrolysis) impact on adsorptive characteristics of the GAC was limited.

Electrochemical fingerprinting of cephalosporin antibiotics and its applications for investigations of hydrolysis behavior

Cephalosporin, as one of the most widely used antibiotics, study of its hydrolysis process is important for predicting their environmental persistence. Two critical factors are considered has the first priority, which are hydrolysis rate constant (kh) and half-life (t1/2). To date, many efforts have been made by using various analytical techniques to obtain the data for calculating kh and t1/2. However, the typical techniques such as UV/vis spectrophotometry and liquid chromatography are of significant challenges like low accuracy and timely operations. Herein, we explored an electrochemical method by identifying the characteristic peaks with the same parent nuclear structure through square wave voltammetry (SWV). This proposed electrochemical fingerprinting was able to track the hydrolysis of intact cephalosporin molecules, β-lactam ring, and transformation product. The kh and t1/2 of cefadroxil (CDX) under pH = 7 and 25 °C by electrochemical (0.0640 d−1 and 11.0 d) were consistent with those of high-performance liquid chromatography-UV/vis (HPLC-UV/vis) (0.0660 d−1 and 10.7 d). The t1/2 ranged from 3.40 to 36.2 d, 7.33 d–43.7 d and 9.63 d–45.3 d for base-catalyzed, neutral pH and acid-catalyzed hydrolysis hydrolyzed, respectively, indicating that base-catalyzed hydrolysis rates were the greatest under alkaline conditions. Meanwhile, hydrolysis rates increased 2.50–3.60-fold for every 10 °C raise in temperature. Besides, the electrochemical fingerprinting could realize cephalosporin and β-lactam ring hydrolysis rates close to 100% in-situ hydrolysis process monitoring. This present work provides a powerful technology for understanding the environmental fate and predicting the environmental behavior of antibiotics with fast, high accuracy, specific recognition, and in situ monitoring.

Prediction model on hydrolysis kinetics of phthalate monoester: A density functional theory study

As primary degradation products of phthalate esters, phthalate monoesters (MPEs) have been widely detected in various aquatic environments and drawn growing toxicological concerns. Hydrolysis kinetics that is of importance for assessing environmental persistence of chemicals remain elusive for MPEs. Herein, kinetics of base-catalyzed and neutral hydrolysis for 18 MPEs with different leaving groups was investigated by density functional theory calculation. Results indicate that MPEs with leaving groups having pKa of <10 prefer dissociative transition states. MPEs are more persistent than their parents, and their hydrolysis half-lives were calculated to vary from 3.4 min to 79.2 years (pH = 7–9). A quantitative structure-activity relationship model was developed for predicting the hydrolysis kinetics parameters. It was found that pKa of the leaving groups and electronegativity of the MPEs are key factors determining the hydrolysis kinetics. This work may lay a theoretical foundation for better understanding the chemical process that governs MPE persistence in aquatic environments.

Decomposition of Dimethoate and Omethoate in Aqueous Solutions — Half-Life, Eco-Neurotoxicity Benchmarking, and Mechanism of Hydrolysis

Decomposition of Dimethoate and Omethoate in Aqueous Solutions — Half-Life, Eco-Neurotoxicity Benchmarking, and Mechanism of Hydrolysis

Potential Climate Change Impacts on the Abiotic Degradation of Acyl-Homoserine Lactones in the Fluctuating Conditions of Marine Biofilms

Marine biofilms are functional communities that shape habitats by providing a range of structural and functional services integral to coastal ecosystems. Impacts of climate change on biological aspects of such communities are increasingly studied, but impacts on the chemicals that mediate key interactions of biofilm organisms have largely been overlooked. Acyl-homoserine lactones (AHLs), crucial bacterial signals within biofilms, are known to degrade through pH and temperature-dependent hydrolysis. However, the impact of climate change on AHLs and thus on biofilm form and function is presently unknown. This study investigates the impact of changes in pH and temperature on the hydrolysis rate, half-life time and quantitative abundance of different AHLs on daily and seasonal timescales for current conditions and future climate change scenarios.We established the mathematical relationships between pH, hydrolysis rates/half-life times and temperature, which revealed that natural daily pH-driven changes within biofilms cause the greatest fluctuations in AHL concentration (up to 9-fold). Season-dependant temperature enhanced or reduced the observed daily dynamics, leading to higher winter and lower summer concentrations and caused a shift in timing of the highest and lowest AHL concentration by up to two hours. Simulated future conditions based on climate change projections caused an overall reduction of AHL degradation and led to higher AHL concentrations persisting for longer across both the daily and seasonal cycles.This study provides valuable quantitative insights into the theoretical natural dynamics of AHL concentrations. We highlight critical knowledge gaps on the scale of abiotic daily and seasonal fluctuations affecting estuarine and coastal biofilms and on the biofilms’ buffering capacity. Detailed experimental studies of daily and seasonal dynamics of AHL concentrations and assessment of the potential implications for a suite of more complex interactions are required. Substantial fluctuations like those we show in this study, particularly with regards to concentration and timing, will likely have far reaching implications for fundamental ecosystem processes and important ecosystem services such as larval settlement and coastal sediment stabilisation.

Chiral perspective evaluations: Enantioselective hydrolysis of 6PPD and 6PPD-quinone in water and enantioselective toxicity to Gobiocypris rarus and Oncorhynchus mykiss.

As a ubiquitous tire antidegradant, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is persistently released into the environment. It is highly toxic to aquatic organisms, and its transformation product 6PPD-quinone (6PPD-Q), is "very highly toxic" to Oncorhynchus kisutch at a median lethal concentration (LC50) of<0.1ng/mL. Notably, 6PPD and 6PPD-Q are chiral compounds. Here, enantioselective evaluations, including hydrolysis and acute toxicity were conducted after preparing the enantiomer, confirming the enantiomer absolute configuration and establishing enantioseparation methods. In the 6PPD hydrolysis experiments, the products 6PPD-Q, phenol, 4-[(1,3-dimethylbutyl)amino]- (4-DBAP) and 4-hydroxydiphenylamine (4-HDPA) were detected. In different water solutions, the hydrolysis of 4-DBAP and 4-HDPA was very fast (0.87-107h), while the 6PPD-Q hydrolysis half-lives (12.8-16.3 d) were significantly longer than 6PPD (4.83-64.1h). At the enantiomeric level, no enantioselective hydrolysis and conversion occurred. R-6PPD generated R-6PPD-Q, and S-6PPD generated S-6PPD-Q, and the formation rate of S-6PPD-Q was 1.77 times faster than R-6PPD-Q. In terms of the enantioselective toxicity, the 6PPD enantiomer was highly toxic to China-specific Gobiocypris rarus (LC50, 162-201ng/mL), and it had no enantioselective difference. 6PPD-Q was "very highly toxic" (LC50, 1.66-4.31ng/mL) to Oncorhynchus mykiss, which is of commercial importance, and the toxicities of rac-6PPD-Q and S-6PPD-Q were 1.9 and 2.6 times higher than R-6PPD-Q. Furthermore, the formation concentrations of S-6PPD-Q and R-6PPD-Q in 6PPD water solutions were higher than the LC50 values of O. kisutch and O. mykiss, and the toxicity of 6PPD-Q was highly species-specific, which should raise concern. These results provide important information for environmental risk assessments of 6PPD and 6PPD-Q, especially from the perspective of enantiomers.

Aggregation-Suppressed Porous Processable Hexa-Zirconium/Polymer Composites for Detoxification of a Nerve Agent Simulant

We describe a composite in which reactive hexa-nuclear zirconium (Zr6) clusters were encapsulated in the micropores of processable polymers of intrinsic microporosity (PIMs). By varying the amount of Zr6 clusters in PIMs, it was possible to tune the loading of Zr6 in two polymer matrices: the pristine PIM-1 and the amidoxime-functionalized PIM (PIM-1-AO). Aggregation of Zr6 clusters was suppressed in both Zr6@PIM composites to achieve improved hydrolysis performance of a nerve agent simulant, dimethyl 4-nitrophenylphosphate (DMNP). Low-loading Zr6@PIM-1-AO was found to be the best catalyst, with a DMNP hydrolysis half-life of less than 1 h, which is comparable to some zirconium metal–organic frameworks (Zr-MOFs) at higher catalyst loading. Further, these composites can be electrospun into reactive nanofibers. This demonstrates a new route to apply porous polymers as matrices to encapsulate, stabilize, and utilize the reactivity of soluble Zr6 clusters, which could act as effective candidate materials for the fabrication of personal protective equipment (PPE) against nerve agents.

Hydrolysis and photolysis of flupyradifurone in aqueous solution and natural water: Degradation kinetics and pathway

Flupyradifurone (FPO) easily spreads to the water environment after application because of its high solubility in water (3200 mg/L, 20 °C), but as a novel neonicotinoid pesticide, its environmental fate study is still lacking. Here, laboratory experiments were conducted to investigate the degradation kinetics and pathways of FPO in aqueous solutions and natural waters. The results showed that FPO was fairly stable in water under natural conditions (the hydrolysis half-lives at 15 °C, 25 °C, and 35 °C were >150 d, and the photolysis half-lives under sunlight were >168 h). However, FPO was photodegraded rapidly under ultraviolet (UV) light (half-lives of 2.37–3.81 min). Then, indirect photolysis under UV light was examined with the addition of photosensitizers, revealing that direct photolysis is the main FPO degradation pathway in water, and the contribution of indirect photolysis was limited. Moreover, two photoproducts were separated, purified and collected via preparative HPLC, and identified via high resolution mass spectrometry. Then, the plausible photolysis pathway was proposed. The results of this study will contribute to a better understanding of the fate of FPO in the water environment.

Occurrence and fate of chlorinated methylsiloxanes in surrounding aqueous systems of Shengli oilfield, China

Mono-chlorinated products of cyclic volatile methylsiloxanes (cVMS), i.e., Monochlormet-hylheptamethylcyclotetrasiloxane [D3D(CH2Cl)], monochlormethylnonamethylcyclopenta-siloxane [D4D(CH2Cl)], and monochlormethylundemethylcyclohexasiloxane [D5D(CH2Cl)], were detected in water [<LOQ (Limit of quantitation) -86.3 ng/L, df (detection frequency) = 23%-38%, n=112] and sediment samples [<LOQ-504 ng/g dw (dry weight), df = 33%-38%, n=112] from 16 lakes located in Shengli oilfield of China, and had apparent increasing trends (31%-34% per annum) in sediments during Year 2014-2020. Simulated experiments showed that chloro-cVMS in sediment-water system had approximately 1.7-2.0 times slower elimination rates than parent cVMS. More specifically, compared with those of parent cVMS, volatilization (86-2558 days) and hydrolysis (135-549 days) half-lives of chloro-cVMS were respectively 1.3-2.0 and 1.8-2.1 times longer. In two species of freshwater mussels (n=1050) collected from six lakes, concentrations of chloro-cVMS ranged from 9.8-998 ng/g dw in Anodonta woodiana and 8.4-970 ng/g dw in Corbicula fluminea. Compared with parent cVMS, chloro-cVMS had 1.1-1.5 times larger biota-sediment accumulation factors (2.1-3.0) and 1.1-1.7 times longer half-lives (13-42 days). Their stronger persistence in sediment and bioaccumulation in freshwater mussels suggested that environmental emission, distribution and risks of chloro-cVMS deserve further attention.

The chemistry of branched condensed phosphates

Condensed phosphates may exist as linear, cyclic or branched structures. Due to their important role in nature, linear polyphosphates have been well studied. In contrast, branched phosphates (ultraphosphates) remain largely uncharacterised, because they were already described in 1950 as exceedingly unstable in the presence of water, epitomized in the antibranching-rule. This rule lacks experimental backup, since, to the best of our knowledge, no rational synthesis of defined ultraphosphates is known. Consequently, detailed studies of their chemical properties, reactivity and potential biological relevance remain elusive. Here, we introduce a general synthesis of monodisperse ultraphosphates. Hydrolysis half-lives up to days call the antibranching-rule into question. We provide evidence for the interaction of an enzyme with ultraphosphates and discover a rearrangement linearizing the branched structure. Moreover, ultraphosphate can phosphorylate nucleophiles such as amino acids and nucleosides with implications for prebiotic chemistry. Our results provide an entry point into the uncharted territory of branched condensed phosphates.

Mechanism of degradation of propargyl alcohol by acid-catalysed hydrolysis and corrosion inhibition efficiency of propargyl alcohol intermediates for carbon steel in hydrochloric acid

Acetylenic alcohols are one of the most important groups of film-forming corrosion inhibitors for carbon steel in hydrochloric acid (HCl). The inhibition mechanism of acetylenic alcohols has been widely discussed for more than 50 years, however, it is not well-understood, particularly with regard to the chemical degradation reactions of acetylenic alcohols in HCl solution. In the present paper, proton nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) techniques were used to investigate the mechanism and the rate of degradation of propargyl alcohol in 3.6–10.8 M HCl at 20–95 °C. Several water-soluble products, such as 1-hydroxypropan-2-one, 2-chloroprop-2-en-1-ol, 2,2-dichloropropan-1-ol and 2-chloropropane-1,2-diol were formed via the electrophilic acid-catalysed addition of HCl and water to the alkyne. Some intermediates further polymerize to form water-insoluble polymers, such as poly (propargyl alcohol), poly (allyl alcohol) and poly (acrolein). The hydrolysis half-life constants of propargyl alcohol decreased with increasing HCl concentration and temperature. The inhibition efficiency (η) of propargyl alcohol and its precursors for carbon steel in 3.6 M and 7.83 M HCl was studied. The critical role of acrolein intermediates on the corrosion performance of propargyl alcohol in hydrochloric acid was identified. Products of propargyl alcohol hydrolysis, 1-hydroxypropan-2-one and 2-chloroprop-2-en-1-ol are poor corrosion inhibitors. However, acrolein and its reactive intermediates are good corrosion inhibitors with inhibitor efficiency, η in the range from 97.69 ± 0.4 % for fresh acrolein to η = 97.94 ± 0.8 % for aged acrolein.

Insights into Catalytic Hydrolysis of Organophosphonates at M-OH Sites of Azolate-Based Metal Organic Frameworks.

Organophosphorus nerve agents, a class of extremely toxic chemical warfare agents (CWAs), have remained a threat to humanity because of their continued use against civilian populations. To date, Zr(IV)-based metal organic framework (MOFs) are the most prevalent nerve agent hydrolysis catalysts, and relatively few reports disclose MOFs containing nodes with other Lewis acidic transition metals. In this work, we leveraged this synthetic tunability to explore how the identity of the transition metal node in the M-MFU-4l series of MOFs (M = Zn, Cu, Ni, Co) influences the catalytic performance toward the hydrolysis of the nerve agent simulant dimethyl (4-nitrophenyl)phosphate (DMNP). Experimental studies reveal that Cu-MFU-4l exhibits the best performance in this series with a half-life for hydrolysis of ∼2 min under these conditions. In contrast, both Ni- and Co-MFU-4l demonstrate significantly slower reactivity toward DMNP, as they both fail to surpass 30% conversion of DMNP after 1 h under analogous conditions. Further modification of the active site within Cu-MFU-4l is possible, and we found that although the identity of the anion coordinated to the Cu(II)-X (X = Cl-, HCOO-, ClO4-, NO3-) active site has little influence on the catalytic performance, reduction of the Cu(II) sites yields nodes that contain Cu(I) ions in a trigonal geometry with open metal sites, leading to remarkable catalytic activity with a half-life for hydrolysis less than 2 min. Computational studies indicate the Cu(I) sites exhibit stronger binding affinities than Cu(II) to both water and DMNP, which corroborates the experimental results.

Controllable multi-phase protein release from in-situ hydrolyzable hydrogel

Using hydrogels to control the long-term release of protein remains challenging, especially for in-situ forming formulations. The uncontrollable burst release in the initial phase, the halted release in the subsequent phase, and the undesired drug dumping at the late stage are some obstacles hydrogel-based depots commonly encounter. In this study, we report hydrolyzable dextran-based hydrogels crosslinked by Michael addition to demonstrate a systematic solution to solve these problems. First, the polymer concentration was used as the critical parameter to control the proportion of releasable versus physically trapped protein molecules in the initial hydrogel meshwork. Subsequently, the dynamic change of the hydrogel meshwork was modulated by the crosslinking density and the cleavage rate of ester linkers. To this end, we designed and synthesized a series of ester linkers with hydrolytic half-life ranging from 4 h to 4 months and incorporate them into the hydrogel. Controlled release was demonstrated for model proteins varied in size, including lysozyme (14 kDa), bovine serum albumin (66 kDa), immunoglobulin G (150 kDa), and bevacizumab (149 kDa). In particular, sustained release of IgG ranging from 10 days to 8 months was achieved. Lastly, a tunable multi-phase release profile was made feasible by incorporating multiple ester linkers into one hydrogel formulation. The linker's half-life determined each phase's release duration, and the linkers' mixing ratio determined the corresponding release fraction. The reported hydrogel design engenders a versatile platform to address the needs for long-term and readily adjustable protein release for biomedical applications.

The Monte Carlo method to build up models of the hydrolysis half-lives of organic compounds

ABSTRACT The hydrolysis of organic chemicals such as pesticides, pollutants, or drugs can affect the fate and behaviour of environmental contaminants, so it is of interest to evaluate the stability of substances in water for various purposes. For the registration of organic compounds in Europe, information on hydrolysis must be presented. However, the experimental measurements of all chemicals would require enormous resources, and computational models may become attractive. Applying the CORAL software (http://www.insilico.eu/coral) quantitative structure-property relationships (QSPRs) were built up to model hydrolysis. The 2D-optimal descriptor is calculated with so-called correlation weights for attributes of simplified molecular input-line entry systems (SMILES). The correlation weights are obtained as results of the special Monte Carlo optimization. The nature of (five- and six-member) rings is an important component of this approach. Another important component is the atom pair proportions for nitrogen, oxygen, and sulphur. The statistical quality of the best model is: n = 44, r 2 = 0.74 (training set); n = 14, r 2 = 0.75 (calibration set); and n = 12, r 2 = 0.80 (validation set).

Cyclic Phenylmethylsiloxane Oligomers in Municipal Landfills and Their Elimination Mechanisms in Leachate Treatment Processes.

This study investigated some sources and elimination mechanisms of phenylmethylsiloxanes in landfill leachates. During a 20-day leaching experiment for electronic wastes collected from one Chinese landfill, significant release (4.9 ng/L to 1.3 μg/L) of cis-/trans-2,4,6-triphenyl-2,4,6-trimethylcyclotrisiloxanes (cis-P3 and trans-P3) and cis-/trans-2,4,6,8-tetraphenyl-2,4,6,8-tetramethylcyclotetrasiloxanes (cis-P4 and trans-P4a,b,c) in simulated leachates was found. From January 2017 to December 2018, P3 and P4 isomers were detected in raw leachates from active cells [<LOQ-990 ng/L, detection frequency (df) = 67-100%] and closed cells (<LOQ-282 ng/L, df = 2.1-98%) of this landfill. Generally, mean mass loads of total phenylmethylsiloxanes in raw leachates were larger in the summer (380 mg/d) and winter (295 mg/d) for active cells, while they decreased from 36.1 mg/d to <LOQ for closed cells during the entire period. During leachate treatment processes, sorption to sludge was responsible for major removal (64-84%) of phenylmethylsiloxanes, while Fenton treatment accounted for 8.5-25% removal. Simulated Fenton experiments indicated that hydroxylation half-lives of P3 (1.3-1.5 h) and P4 (0.65-0.86 h) were 15-91 times faster than their hydrolysis half-lives (22-59 h, pH 3.5). Furthermore, monohydroxylated P4 isomers with a hydroxyphenyl group had larger (3.2-3.9 times) concentrations than those with a hydroxymethyl group, meaning that a phenyl group may be more likely to be hydroxylated than a methyl group.

Prediction Models on pKa and Base-Catalyzed Hydrolysis Kinetics of Parabens: Experimental and Quantum Chemical Studies.

Parabens for which the molecules contain hydrolytic and ionizable groups, are emerging pollutants due to their ubiquity in the environment. However, lack of pKa and second-order base-catalyzed hydrolysis kinetics (kB) values limits their environmental persistence assessment. Herein, six parabens were selected as reference compounds for which the pKa and kB values were measured experimentally. A semiempirical quantum chemical (QC) method was selected to calculate pKa of the parabens, and density functional theory (DFT) methods were selected to calculate kB for neutral and anionic forms of the parabens, by comparing the QC-calculated and determined values. Combining the QC-calculated and experimental pKa and kB values, quantitative structure-activity relationships with determination coefficients (R2) being 0.947 and 0.842 for the pKa and kB models, respectively, were developed, which were validated and could be employed to efficiently fill the kB and pKa data gaps of parabens within applicability domains. The base-catalyzed hydrolysis half-lives were estimated to range from 6 h to 1.52 × 106 years (pH 7-9, 25 °C), further necessitating the in silico models due to the tedious and onerous experimental determination, and the huge number of hydrolyzable and ionizable chemicals that may be released into the environment.