Structure-activity Relationship Research Articles

Current advances in the structure-activity relationship (SAR) analysis of the old/new 18-kDa translocator protein ligands.

The translocator protein 18kDa (TSPO) is a crucial external mitochondrial protein involved in cholesterol translocation, which is essential for steroid production. As a primary marker of neuroinflammation, TSPO has been implicated in the development and progression of various neurodegenerative and neuropsychiatric disorders. This review highlights the structural diversity of TSPO ligands, many of which have undergone modifications from selective central benzodiazepine receptor (CBR) ligands to enhance their affinity for TSPO. The paper discusses the significant advancements in the design of these ligands, emphasizing their binding efficacy and specificity. Additionally, it provides an update on the progress of several TSPO ligands that have advanced to clinical trials. The review aims to elucidate the structure-activity relationships (SAR) that govern the interaction between TSPO and its ligands, thereby offering insights into the development of new therapeutic agents targeting TSPO for the treatment of neuroinflammatory conditions. Overall, this work provided an update on previous finding and serves as a valuable resource for researchers in the field.

Tandem Electroreduction of CO2 to C2+ Products based on M-SACs/Cu Catalyst.

Electrochemical CO2 reduction reaction (ECO2RR) is considered a highly promising method to produce high-value chemicals and fuels, contributing significantly the artificial carbon balance. Cu species exhibit a distinct role in the formation of C2+ products characterized by enhanced energy density. The limited selectivity of C2+ products, along with the inferior stability, and high overpotential demonstrated by single-component Cu catalysts, hinders their applicability in industrial-scale production. The implementation of a tandem strategy, which involves coupling the CO2-to-CO pathway using metal single-atom catalysts (M-SACs), etc., with the CO-to-C2+ conversion on Cu species, represents a novel approach for the efficient generation of C2+ products. Given the high cost and restricted availability of noble metals, M-SACs have attracted substantial interest in tandem systems. The systematic analysis of the design principles and structure-activity relationship is essential for the advancement of M-SACs/Cu-based tandem catalysts. Here we first introduce various prevalent design strategies of M-SACs/Cu-based tandem catalysts for ECO2RR and then systematically summarize the latest advancements of M-SACs/Cu-based tandem system, encompassing metal-organic frameworks/Cu (MOFs/Cu), covalent organic frameworks/Cu (COFs/Cu), and nitrogen-doped carbon support transition metal single atomic materials/Cu (M-N-C/Cu). Lastly, we discuss the challenges and opportunities with the design and construction of M-SACs/Cu-based tandem catalysis for ECO2RR.

Kinact/KI Value Determination for Penicillin-Binding Proteins in Live Cells.

Penicillin-binding proteins (PBPs) are an essential family of bacterial enzymes that are covalently inhibited by the β-lactam class of antibiotics. PBP inhibition disrupts peptidoglycan biosynthesis, which results in deficient growth and proliferation, and ultimately leads to lysis. IC50 values are often employed as descriptors of enzyme inhibition and inhibitor selectivity, but can be misleading in the study of time-dependent, covalent inhibitors. Due to this disconnect, the second-order rate constant, kinact/KI, is a more appropriate metric of covalent-inhibitor potency. Despite being the gold standard measurement of potency, kinact/KI values are typically obtained from in vitro assays, which limits assay throughput if investigating an enzyme family with multiple homologues (such as the PBPs). Therefore, we developed a whole-cell kinact/KI assay to define inhibitor potency for the PBPs in Streptococcus pneumoniae using the fluorescent, activity-based probe, Bocillin-FL. Our results align with in vitro kinact/KI data and show a comparable relationship to previously established IC50 values. These results support the validity of our in vivo kinact/KI method as a means of obtaining β-lactam potency for a suite of PBPs to enable structure-activity relationship studies.

Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application.

Antrodia camphorata is a valued and scarce parasitic mushroom that exclusively proliferates on the inner cavity wall of the endangered tree Cinnamomum kanehirai Hay (Lauraceae), endemic to Taiwan. Historically, this fungus has been utilized in traditional medicine to treat liver cancer, diarrhea, abdominal pain, hypertension, and food and drug intoxication, among other ailments. Literature searches were performed in scientific databases. The results were compiled from peer-reviewed studies; the search was refreshed through January 2024 to incorporate the most recent research. In vitro studies have revealed that Antrodia camphorata possesses various pharmacological properties that prevent cancer, reduce inflammation, and improve liver function. This medicinal mushroom contains unique ergostane-type triterpenoids known as antcins, which exhibit numerous pharmacological properties. Seven naturally occurring methyl analogs of antcins have been identified so far. In this article, we reviewed and analyzed the properties of methyl antcinate A (MAA), a constituent of Antrodia camphorata and methyl derivative of antcin A. MAA has demonstrated important anti-apoptotic, anti-inflammatory, and gastro-protective properties, as well as significant anti-tumor, anti-cancer, and cytotoxic activities. The anti-cancer effect of MAA in various cancers is attributed to its ability to modulate signaling cascades in apoptotic pathways. A significant challenge is to initiate preclinical and clinical trials to assess its anti-tumor action in vivo, as this data is currently missing. Additionally, future research on the structure-activity relationship of antcins and their derivatives is expected to support their development as therapeutic agents for clinical use.

Optimization and Biological Evaluation of Novel 1H-Pyrrolo[2,3-c]pyridin Derivatives as Potent and Reversible Lysine Specific Demethylase 1 Inhibitors for the Treatment of Acute Myelogenous Leukemia.

Lysine-specific demethylase 1 (LSD1) plays a vital role in the epigenetic regulation of various cancers, making it a promising therapeutic target for anticancer treatments. Herein, we designed and synthesized a novel series of 1H-pyrrolo[2,3-c]pyridin derivatives as potent LSD1 inhibitors. A detailed structure-activity relationship exploration was carried out to discover multiple derivatives with nanomolar enzymatic IC50 values. Further biological evaluation demonstrated that these compounds acted as selective and reversible LSD1 inhibitors. The representative compounds exhibited highly potent antiproliferative activity against both AML (MV4-11 and Kasumi-1) and SCLC (NCI-H526) cell lines. Additionally, they effectively activated CD86 mRNA expression in MV4-11 cells and induced differentiation of AML cell lines. Notably, the most promising compound 23e showed a favorable oral PK profile and effectively suppressed the tumor growth in an AML xenograft model. Overall, our medicinal chemistry efforts provide compound 23e as a lead compound for developing LSD1 inhibitors for the treatment of AML and other advanced malignancies.

Synthesis and Fungicidal Activities of Coumarin Derivatives as Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase inhibitors (SDHIs) have been developed to the fastest growing family of fungicides. To develop novel SDH inhibitors, twenty-seven novel non-amides coumarin derivatives were designed, synthesized and characterized .The bioassay revealed that most of the target compounds exhibited significant antifungal activity against Botrytis cinerea in vitro. Notably, compounds 1a and 2c with EC50 values of 0.92 μg/mL and 0.52 μg/mL, respectively，which were better than that of positive control chlorothalonil (EC50 =3.14 μg/mL).Moreover, in vivo antifungal assay results showed that compound 2c could observably inhibit the growth of B. cinerea on Kuerla pears with remarkable protective at a dosage of 200 μg/mL. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) investigation indicated that compound 2c significantly damaged the cell structures of B. cinerea mycelium. 3D-QSAR models were analyzed structure-activity relationships of all target compounds. Furthermore, molecular docking revealed that compound 2c was able to bind closely to the receptor protein of SDH. These results demonstrated that compound 2c may be potential candidate for novel SDH inhibitors.

Novel Meta-Diamide Derivatives Bearing Triazole: Design, Synthesis and Bioactivity.

In searching for novel insecticide lead,20new meta-diamidecompounds containingtriazole were designed and synthesized regardingCyproflanilide aslead compound.All the compounds were characterized by 1HNMR,13CNMR and HRMS.In preliminary bioassay, we found that one of the compounds: N-(cyclopropylmethyl)-N-(5-((2,6-dibromo-4-(1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl)phenyl)carbamoyl)-2-(1H-1,2,4-triazol-1-yl)phenyl)-6-(trifluoromethyl) nicotinamide(16a) had high activity against the target organism Plutella xylostellaat 1 mg/L and against the target organism Mythimna separataat 2 mg/L. It is obviously superior to theknowncompoundsⅠaand Ⅰb, and itisequivalent to cyproflanilide, the LC50values of the compound against P. xylostella and M. separata were 0.90 mg/L and 0.64 mg/L respectively. It is providing important clues for subsequent structure-activity relationship studies. From this, we explored the structure-activity relationship of these compounds. Through comprehensive analysis of their structural characteristics and insecticidal activity data, we found that different halogen substituents on benzene ring and different aromatic substituents on amino group in the compound had significant effects on insecticidal activity. This has certain guiding significance for further structural optimization and activity enhancement.

Discovery of Potent and Selective Pyridone-Based Small Molecule Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains.

Kinetic stabilization of amyloidogenic immunoglobulin light chains (LCs) through small molecule binding may become the first treatment for the proteinopathy component of light chain amyloidosis (AL). Kinetic stabilizers selectively bind to the native state over the misfolding transition state, slowing denaturation. Prior λ full-length LC dimer (FL LC2) kinetic stabilizers exhibited considerable plasma protein binding. We hypothesized that the coumarin "aromatic core" of the stabilizers was responsible for the undesirable plasma protein binding. Here, we describe structure-activity relationship (SAR) data initially focused on replacing the coumarin aromatic core. 2-pyridones proved suitable replacements. We subsequently optimized the "anchor substructure" in the context of 2-pyridones, resulting in potent λ FL LC2 kinetic stabilizers exhibiting reduced plasma protein binding. The 3-methyl- or 3-ethyl-3-phenylpyrrolidine-2-pyridone scaffold stabilized multiple AL patient-derived λ FL LC2s in human plasma. This, coupled with X-ray crystallographic data, indicates that 3-alkyl-3-phenylpyrrolidine-2-pyridone-based stabilizers are promising candidates for treating the proteinopathy component of AL.

Insights into the Removal of Organic Contaminants by Co-CeO2 Nanocatalysts via CaCO3 Activation: Performance, Kinetic, and Mechanism.

The advanced oxidation process based on S(IV) has garnered increasing attention, owing to its efficiency in degrading contaminants. Here, a cobalt-doped cerium oxide catalyst (Co-CeO2) was employed to activate calcium sulfite (CaSO3) for imidacloprid degradation. The Co-CeO2 catalyst was characterized by using SEM, BET, XRD, and XPS techniques to analyze its structural and chemical properties. XPS analysis revealed the presence of Co0, Co2+, and Co3+ species in the Co-CeO2 catalyst. Compared to the CeO2/CaSO3 system, the Co-CeO2/CaSO3 system significantly enhanced the degradation rate of imidacloprid from 5.00% to 94.01%. Scavenging experiments, in conjunction with electron paramagnetic resonance spectroscopy, identified hydroxyl radicals (•OH), sulfate radicals (SO4•-), superoxide radicals (O2•-), sulfite radicals (SO3•-), and singlet oxygen (1O2) as the primary reactive species responsible for the degradation of imidacloprid within the Co-CeO2/CaSO3 system. Density functional theory calculation analysis was employed to investigate the specific sites of imidacloprid attacked by reactive oxygen species, proposing four potential degradation pathways. Furthermore, the Ecological Structure Activity Relationships (ECOSAR) program predicted a significant diminution in the toxicity of intermediate products compared to imidacloprid. Even after five cycles, Co-CeO2 maintained an excellent removal efficiency of 86.35%.

Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.

Binding multiple sites within proteins with bivalent compounds is a strategy for developing uniquely active agents. A new class of dual-site inhibitors has emerged targeting the epidermal growth factor receptor (EGFR) anchored to both the orthosteric (ATP) and allosteric sites. Despite proof-of-concept successes, enabling selectivity against oncogenic activating mutations has not been achieved and classifying these inhibitors among kinase inhibitors remains underexplored. This study investigates the structure-activity relationships, binding modes, and biological activity of ATP-allosteric bivalent inhibitors (AABIs). We find that AABIs selectively inhibit drug-resistant EGFR mutants (L858R/T790M and L858R/T790M/C797S) by anchoring a methyl isoindolinone moiety along the αC-helix channel of the allosteric site. In contrast, related Type I1/2 inhibitors target wild-type EGFR but are less effective against resistant mutants. This shift in selectivity demonstrates that mutant-selective AABIs classify as "Type V" bivalent inhibitors.

A Knowledge-Based Molecular Single-Source Precursor Approach to Nickel Chalcogenide Precatalysts for Electrocatalytic Water, Alcohol, and Aldehyde Oxidations.

The development and comprehensive understanding of nickel chalcogenides are critical since they constitute a class of efficient electro(pre)catalysts for the oxygen evolution reaction (OER) and value-added organic oxidations. This study introduces a knowledge-based facile approach to analogous NiE (E = S, Se, Te) phases, originating from molecular β-diketiminato [Ni2E2] complexes and their application for OER and organic oxidations. The recorded activity trends for both target reactions follow the order NiSe > NiS > NiTe. Notably, NiSe displayed efficient performance for both OER and the selective oxidation of benzyl alcohol and 5-hydroxymethylfurfural, exhibiting stability in OER for 11 days under industrially pertinent conditions. Comprehensive analysis, including quasi in situ X-ray absorption and Raman spectroscopy, in combination with several ex situ techniques, revealed a material reconstruction process under alkaline OER conditions, involving chalcogen leaching. While NiS and NiSe experienced full chalcogen leaching and reconstruction into NiIII/IV oxyhydroxide active phases with intercalated potassium ions, the transformation of NiTe is incomplete. This study highlights the structure-activity relationship of a whole series of analogous nickel chalcogenides, directly linking material activity to the availability of active sites for catalysis. Such findings hold great promise for the development of efficient electrocatalysts for a wide range of applications, impacting various industrial processes and sustainable energy solutions.

4-Substituted-2-Thiazole Amides as Viral Replication Inhibitors of Alphaviruses.

2-(Methylthio)-N-(4-(naphthalen-2-yl)thiazol-2-yl)nicotinamide 1 was identified as an inhibitor against Chikungunya virus (CHIKV) with good antiviral activity [EC50 = 0.6 μM; EC90 = 0.93 μM and viral titer reduction (VTR) of 6.9 logs at 10 μM concentration] with no observed cytotoxicity (CC50 = 132 μM) in normal human dermal fibroblast (NHDF) cells. Structure-activity relationship (SAR) studies to further improve the potency, efficacy, and drug-like properties of 1 led to the discovery of a new potent inhibitor N-(4-(3-((4-cyanophenyl)amino)phenyl)thiazol-2-yl)-2-(methylthio)nicotinamide 26, which showed a VTR of 8.7 logs at 10 μM against CHIKV and an EC90 of 0.45 μM with considerably improved MLM stability (t1/2 = 74 min) as compared to 1. Mechanism of action studies show that 26 inhibits alphavirus replication by blocking subgenomic viral RNA translation and structural protein synthesis. The in vivo efficacy studies of compound 26 on CHIKV infection in mice are reported.

Design of Novel Acat Inhibitors as Potent Anti-Hyperlipidemic Agents Using Chemometric Approaches

Aim: A 2D QSAR study of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT) inhibitors revealed that electronic, topological, and steric properties are important structural features required for activity against ACAT. Background: In order to interpret the evidence encrypted by the molecular structure of the compounds, a standard physicochemical descriptors-centered, and Quantitative Structure-Activity Relationship (QSAR) approach was implemented on a data set of Indoline derivatives were reported to be acyl-coenzyme A (CoA): cholesterol acyltransferase ACAT inhibitors. Objective: The ACAT enzyme plays an important role in the absorption of dietary cholesterol. Therefore, the inhibition of ACAT is a key strategy or primary objective for the treatment of hypercholesterolemia and atherosclerosis. Method: Chemo metric models were designed by inserting a battery of statistical techniques in the current study that demonstrate the linear approaches of analysis, including multiple linear regression (MLR), partial least square PLS, and non-linear methods such as artificial neural networks (ANN). Result: The activity contributions of these molecules were analyzed through regression equation, and the best QSAR model was created with an excellent correlative and predictive ability. Significant statistical values S = 0.35, F = 60.30, r = 0.92, r² = 0.85, r² (CV) = 0.82 of the designed models were obtained using stepwise MLR and a comparable PLS and FFNN model with r² (CV) = 0.82, 0.88 and 0.86 respectively and the relevant descriptors like inertia moment 1 size, Kier Chiv4 (cluster) index, Kier Chiv6(ring) index offered important information regarding this model. Conclusion: The model reveals that inertia moment 1 size, Kier Chiv4 (cluster) index, and Kier Chiv6 (ring) index are prerequisite descriptors to determine other promising ACAT antagonists with high and liable potency against the target. Therefore, these characteristics may be used efficiently for the design and evaluation of active compounds as new ACAT inhibitors thanks to their utilization.

Structure and Biosynthetic Gene Cluster of Sulfated Capsular Polysaccharide from the Marine Bacterium Vibrio sp. KMM 8419

Vibrio sp. KMM 8419 (=CB1-14) is a Gram-negative bacterium isolated from a food-net mucus sample of marine polychaete Chaetopterus cautus collected in the Sea of Japan. Here, we report the structure and biosynthetic gene cluster of the capsular polysaccharide (CPS) from strain KMM 8419. The CPS was isolated and studied by one- and two-dimensional 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of the CPS was about 254 kDa. The CPS consisted of disaccharide repeating units of D-glucose and sulfated and acetylated L-rhamnose established as →2)-α-L-Rhap3S4Ac-(1→6)-α-D-Glcp-(1→. To identify the genes responsible for CPS biosynthesis, whole-genome sequencing of KMM 8419 was carried out. Based on the genome annotations together with the Interproscan, UniProt and AntiSMASH results, a CPS-related gene cluster of 80 genes was found on chromosome 1. This cluster contained sets of genes encoding for the nucleotide sugar biosynthesis (UDP-Glc and dTDP-Rha), assembly (glycosyltransferases (GT)), transport (ABC transporter) and sulfation (PAPS biosynthesis and sulfotransferases) of the sulfated CPS. A hypothetical model for the assembly and transportation of the sulfated CPS was also proposed. In addition, this locus included genes for O-antigen biosynthesis. Further studies of biological activity, the structure–activity relationship in the new sulfated polysaccharide and its biosynthesis are necessary for the development of potent anticancer agents or drug delivery systems.

New Insights into Bioactive Peptides: Design, Synthesis, Structure–Activity Relationship

In recent decades, peptides have attracted significant attention not only from Academia but also from big Pharma as novel potential therapeutic compounds [...]

The herbicidal activities and biochemical characteristics of isolates from Murraya microphylla

The extracts of the twigs and leaves of Murraya microphylla showed different level herbicidal activities against Amaranthus retroffexus and Digitaria sanguinalis. Bioguided isolation was performed to obtain eight pyranocarbazoles (1-8), four coumarins (10-13), two flavones (15 and 16), one dibutyl phthalate (9), and one sterol (14), including a new pyranocarbazole (1) and a new natural product (9). Petri dish assay showed that pyranocarbazoles and coumarins were the main herbicidal components of M. microphylla extract, and their structure–activity relationships were ulteriorly elucidated. As the representatives of pyracarbazole and coumarin, 7 and 10 showed significant herbicidal activity compared with the positive control (Nicosulfuron), with the IC50 values 82.93 and 16.34 μg mL−1 against shoots and roots of A. retroffexus seedling, respectively. Experimental results of morphology, physiology and biochemistry indicated that the inhibition on seed germination by 7 and 10 was mainly related to energy deficiency, while the inhibition of seedling growth was mainly related to decreased chlorophyll content, reduced root hairs, and cell membrane damage. Therefore, 7 and 10 have the potential to develop new plant herbicides directly or as lead compounds.

Imidazo[1,2-A]Pyridine: Potent Biological Activity, SAR and Docking Investigations (2017-2022).

Regarding scientific research, Imidazo[1,2-a] pyridine derivatives are constantly being developed due to the scaffold's intriguing chemical structure and varied biological activity. They are distinctive organic nitrogen-bridged heterocyclic compounds that have several uses in medicines, organometallics and natural products. It has become a vital tool for medicinal chemists. In order to gather scientific information on Imidazo[1,2-a] pyridines derivative, Google, PubMed, Scopus, Google Scholar, and other databases were searched. In the current study, the medicinal value and therapeutic effect of Imidazo[1,2-a] pyridines were investigated using above mentioned databases. The current study analyzed the detailed pharmacological activities of Imidazo[1,2-a] pyridine analogs through literature from diverse scientific research works. Due to its wide range of biological activities, including antiulcer, anticonvulsant, antiprotozoal, anthelmintic, antiepileptic, antifungal, antibacterial, analgesic, antiviral, anticancer, anti-inflammatory, antituberculosis, and antitumor properties, imidazopyridine is one of the most significant structural skeletons in the field of natural and pharmaceutical products. An imidazopyridine scaffold serves as the basis for a number of therapeutically utilized medications, including zolpidem, alpidem, olprinone, zolimidine, and necopidem. This comprehensive study covers the period of the last five years, and it sheds light on the developments and emerging pharmacological actions of Imidazo[1,2-a] pyridines. Additionally, the structure-activity relationship and molecular docking studies are carefully documented throughout the paper, providing medicinal chemists with a clear picture for developing new drugs.

Quinoline and Analogs: Insight into the Synthesis, Biological Activity, Structure-Activity Relationship, and Interaction with Targets

Abstract: Quinoline and its derivatives have been utilized and marketed as antibacterial, antimalarial, anticancer, hypertension, asthma (COPD), etc. The diverse pharmacological properties of quinolone are related to its chemical structure. Nowadays, it is common practice to combine at least two pharmacophores to create a single molecule with powerful pharmacological effects. This helps to synergize pharmacological qualities, enables interaction with several targets, or lessens the negative effects related to them. Various synthetic approaches which have been used in recent times for the synthesis of quinoline and its derivatives are listed in the manuscript with their merits and demerit. The structure-activity relationship relating various pharmacological actions with molecular structure and interaction with several targets has also been highlighted to provide a good comprehension to the researchers for future studies on quinoline.

Cinnamic acid and its derivatives on dipeptidyl peptidase 4: structure-activity relationship and mechanism of inhibition

Dipeptidyl peptidase 4 (DPP4), which breaks down glucagon-like peptide 1 (GLP-1), is closely associated with glucose metabolism, and the inhibition of this enzyme is one of the important targets for the treatment of diabetes. Traditionally cinnamon and bitter melon have been in wide use in diabetes treatment, and cinnamic acid (CIA) as its main ingredient is expected to be an ideal DPP4 inhibitor. In vitro inhibition experiments showed that CIA had the lowest IC50 (33.56 ± 1.13 mM) compared to the other substances in the study, suggesting that it was more effective in inhibiting DPP4. Analyses showed that adding hydroxyl and methyl groups to CIA's aromatic ring reduced its effect on DPP4; CIA and its derivatives were inhibited in a mixed way. With the exception of ferulic acid (FA), CIA and its derivatives quenched the fluorescence of DPP4 via a static quenching mechanism. Thermodynamic parameters show that that the binding of CIA (the most inhibitory compound) to DPP4 was spontaneous and driven by hydrogen bonding. Atomic force microscopy and circular dichroism spectroscopy analyses reveal that upon binding with DPP4, CIA underwent a conformational change. Molecular docking results highlight , while introducing hydroxyl and methoxy groups on the aromatic ring, the superior binding capacity of CIA diminished. The study confirms that CIA is an ideal inhibitor with the highest absolute value of binding energy (-5.8) and the lowest IC50 compared to other substances. By clarifying the inhibition mechanism of DPP4,the study thus provides dietary guidance for diabetic patients.

Insights into the photosensitivity and photobleaching of dissolved organic matter from microplastics: Structure-activity relationship and transformation mechanism

Revealing the structure-activity relationship between physicochemical properties and photoactivities of microplastic dissolved organic matter (MPDOM) is significant for understanding the environmental fate of MPs. Here, we systematically analyzed the physicochemical properties and molecular composition of DOM derived from MPs including polystyrene (PS), polyethylene glycol terephthalate (PET), polyadipate/butylene terephthalate (PBAT), polylactic acid (PLA), polypropylene (PP), and compared their photosensitivity and photobleaching behaviors. Results indicated that PSDOM and PETDOM had more similar properties and compositions, and showed stronger photosensitivity and photobleaching effects than PBATDOM, PLADOM and PPDOM. The [3DOM∗]SS and [1O2]SS varied in the range of 0.31-13.03 × 10-14 and 1.71-5.49 × 10-13M, respectively, which were within the reported range of DOM from other sources. The SUVA254, HIX, AImodwa, Xcwa and lignin/CRAM-like component showed positive correlation with the [3DOM∗]SS, [1O2]SS and Φ3DOM*. The negative correlation between E2/E3 and [3DOM∗]SS was due to the higher proportion of low-molecular weight components in MPDOM. The lignin/CRAM-like component was identified to be the crucial photobleaching-component. The lignin/CRAM-like in PSDOM showed a deepened oxidation degree, while its change trend in PETDOM was from unsaturated to saturated. These findings provide new insights into the relevant photochemical fate of MPDOM.