Reaction Profile Research Articles

Computation‐Guided Scope Exploration of a Conjugate Addition/Truce‐Smiles Cascade Reaction for Scaffold Diversification

Based on the successful application of a nitroaryl transfer cascade reaction in the total synthesis of various monoterpene indole alkaloids proceeding via fused bicyclic intermediate, we investigated analogous cascade reactions involving spiro, bridged, and alternatively fused bicyclic intermediates. Unfortunately, none of these was found to afford the desired nitroaryl transfer product. DFT studies of the original cascade process revealed that the Truce‐Smiles rearrangement is the rate‐determining step. In addition, we found that the subsequent SO2 extrusion is accompanied by retro‐Mannich ring opening, resulting in a stabilized enolate that only recyclizes after activation of the cyclic imine moiety. Computation of the reaction profiles of the proposed alternative cascade reactions showed that the barrier for the Truce‐Smiles rearrangement is unreasonably high for the bridged and alternatively fused systems, but only moderately higher for the five‐membered spiro system. Reasoning that even more electron‐deficient arenesulfonamides should have a lower barrier for the Truce‐Smiles rearrangement, we synthesized the corresponding 2,4‐dinitrobenzenesulfonamide precursor and found that it indeed smoothly undergoes the nitroaryl transfer cascade at room temperature. In this case, however, the cascade reaction produces a cyclic imine product, as the intermediate 2,4‐dinitrophenyl‐substituted enolate is insufficiently nucleophilic to undergo the Mannich cyclization.

A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B

Objective: To compare the therapeutic efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients with chronic Hepatitis-B (CHB). Methods: This retrospective study included 110 patients with CHB who received treatment at The First People’s Hospital of Linping District, Hangzhou from January 2021 to January 2023. Clinical data of the patients were reviewed and the patients were classified according to the treatment received: TDF group (n=53, patients received TDF treatment) and ETV group (n=57, patients received ETV treatment). Hepatitis-B virus deoxyribonucleic acid (HBV DNA) levels, liver function indicators, hepatitis-B e antigen (HBeAg) seroconversion rate, alanine transaminase (ALT) normalization rate, HBV DNA negative conversion rate, overall efficacy, and incidence of adverse reactions were compared. Results: The total efficacy of the treatment in the TDF group was 94.33%, significantly higher than that in the ETV group (78.95%; P<0.05). After the treatment, the HBV DNA levels in both groups decreased compared to pretreatment levels, and were significantly lower in the TDF group compared to the ETV group (P<0.05). Both groups showed significant post-treatment improvement in liver function that was markedly better in the TDF group compared to the ETV group (P<0.05). The HBeAg seroconversion rate, ALT normalization rate, and HBV DNA conversion rate in the TDF group were significantly higher compared to the ETV group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups. Conclusions: Compared with ETV, TDF has comparable adverse reaction profile but has more significant clinical effects in patients with CHB, improving HBeAg seroconversion rate, ALT normalization rate, and HBV DNA negative conversion rate. TDF is associated with lower HBV DNA levels after treatment and better improvements in liver function of patients. doi: https://doi.org/10.12669/pjms.40.10.10307 How to cite this: Wang H, Wu L. A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B. Pak J Med Sci. 2024;40(10):2390-2394. doi: https://doi.org/10.12669/pjms.40.10.10307 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Deuteration and Tritiation of Pharmaceuticals by Non-Directed Palladium-Catalyzed C-H Activation in Heavy and Super-Heavy Water.

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non-directed homogeneous Pd-catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.

Deuteration and Tritiation of Pharmaceuticals by Non‐Directed Palladium‐Catalyzed C−H Activation in Heavy and Super‐Heavy Water

AbstractDeuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non‐directed homogeneous Pd‐catalysis. Aromatic C−H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non‐directed homogeneous Pd‐catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.

Kinetics and Mechanism of PPh3/Ni-Catalyzed, Zn-Mediated, Aryl Chloride Homocoupling: Antagonistic Effects of ZnCl2/Cl.

The Ni/PPh3-catalyzed homocoupling of aryl chlorides in DMF using Zn as the stochiometric reducing agent is one of a general class of Ni-catalyzed processes, where the mechanism has been a matter of long-standing debate. This study re-evaluates prior conclusions and insights. NMR spectroscopy is used to identify [(PPh3)2NiII(Ar)Cl] as a key intermediate and to explore the indirect roles of using Zn as the reductant. The [ZnCl2] coproduct is responsible for several features, including a sequential transmetalation pathway involving [ArZnCl]. [ZnCl2] also abstracts halide from [(PPh3)2NiCl2] to generate [NiIICl(DMF)5]+[ZnCl3(DMF)]-, and in doing so, affects the NiII + Ni0 ↔ 2 NiI speciation. [ZnCl2] thus acts as an accelerator and inhibitor, resulting in mildly sigmoidal reaction profiles. When the [ZnCl2] concentration becomes too high or the phosphine ligand concentration too low, catalysis stalls. Turnover is restored by the addition of further phosphine ligand, or chloride ion. In the presence of an exogenous chloride ion, turnover is rapid, again proceeding via [(PPh3)2NiII(Ar)Cl] but via dinuclear metathesis. The generation of [ZnCl3(DMF)]- results in mutually antagonistic effects between [ZnCl2] and [Cl]- such that turnover proceeds via one mechanism or the other, depending on which species is in excess. The intermediacy of [ArZnCl] suggests a solution to the long-standing anomaly that many other reductants were found to be much less effective than Zn in inducing turnover of Ni/PPh3 catalyzed aryl chloride homocoupling in DMF. The use of DMAc as a solvent in place of DMF inhibits stalling through the steric inhibition of mixed metalate generation.

Reaction force constant as a descriptor of the principle of non-perfect synchronization.

In this study, a small set of 1,3-dipolar cycloaddition reactions that proceed at the same exothermicity is presented. Our main objective was to extend the application of the reaction force constant concept to gain an understanding of the reactivity principles. Inspired by a recent article where we show that the Bell-Evans-Polanyi principle is fulfilled under the condition of an equal degree of (a)synchronicity, here, we demonstrate that the reaction force constant is also a suitable descriptor to quantify the principle of non-perfect synchronization proposed by Bernasconi as a way to understand deviations from the Bell-Evans-Polanyi principle. Reaction profiles , , and were performed at the B3LYP/6-31G(d,p) level of theory. The stabilizing interactions were characterized using the energy decomposition analysis combined with the natural orbitals for chemical valence, EDA-NOCV, method. The present work was done using Gaussian 09 and Multiwfn programs.

Structural Insights and Reaction Profile of a New Unspecific Peroxygenase from Marasmius wettsteinii Produced in a Tandem-Yeast Expression System.

Fungal unspecific peroxygenases (UPOs) are gaining momentum in synthetic chemistry. Of special interest is the UPO from Marasmius rotula (MroUPO), which shows an exclusive repertoire of oxyfunctionalizations, including the terminal hydroxylation of alkanes, the α-oxidation of fatty acids and the C-C cleavage of corticosteroids. However, the lack of heterologous expression systems to perform directed evolution has impeded its engineering for practical applications. Here, we introduce a close ortholog of MroUPO, a UPO gene from Marasmius wettsteinii (MweUPO-1), that has a similar reaction profile to MroUPO and for which we have set up a directed evolution platform based on tandem-yeast expression. Recombinant MweUPO-1 was produced at high titers in the bioreactor (0.7 g/L) and characterized at the biochemical and atomic levels. The conjunction of soaking crystallographic experiments at a resolution up to 1.6 Å together with the analysis of reaction patterns sheds light on the substrate preferences of this promiscuous biocatalyst.

Psychedelic-related deaths in England, Wales and Northern Ireland (1997–2022)

BackgroundPsychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts. AimsThis study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022. MethodsWe analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence. ResultsWe identified 28 cases where psychedelics were implicated (75 %, N = 21) or potentially implicated (25 %, N = 7) in the death; 19 of these involving psychedelic tryptamines (LSD 39 %, N = 11; Psilocybin 21 %, N = 6; DMT 7 %, N = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, N = 5). Most deaths were deemed accidental by the coroner (86 %, N = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, N = 19); and most of the deceased were under 30 years of age (82 %, N = 23). Thematic framework analysis identified nine themes in the deaths across three categories. ‘Polysubstance use’ was the most common theme (82 % of cases, N = 23/28), followed by a suboptimal ‘physical environment’ (70 % of cases where this information was available, N = 14/20). ConclusionsThe profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.

Coupled heat transfer and chemical kinetics in a calcium oxide/hydroxide fixed bed thermochemical energy storage reactor

Among energy storage technologies, thermochemical heat storage despite its unique advantages, remains at a nascent state due to varied technical challenges. One of the key unknowns in the otherwise well-studied calcium oxide/hydroxide chemistry, is a lack of understanding of the possible output power profiles. Here, we investigate the theoretical power output from a fixed-bed, modular, honeycomb-geometry thermochemical energy storage (TCS) reactor based on a calcium oxide/hydroxide, using finite element modeling of heat transfer coupled with reaction kinetics. We calculate the extent of reaction and temperature profiles in a lattice of honeycomb cells that make up the bed, while varying heat transfer related parameters. We find that the size of the unit cell can limit energy discharge, for example, increasing the time to completion for the reaction to ∼7 hours as the cell size increases to 6 cm, even though the reaction kinetics is fast at ∼2 mins. The time constant of the transient power profile increases by a factor of ∼4 as the cell size increases by a factor of ∼3, when considering cells in the nominal size range 2–6 cm. Besides cell size, we investigate how the power profile is affected by the following parameters: the thermal conductivity of the bed, the initial temperature, the material of the cell wall and the heat transfer coefficient of external flows. In particular, we identify the combination of parameters that can vary the power profile on demand to operate the same reactor as either a thermal capacitor or alternately, a thermal battery. This work informs future design possibilities with oxide-hydroxide, solid–gas reaction TCS and provides insight into critical heat transfer parameters.

Comprehensive computational automated search of barrierless reactions leading to the formation of benzene and other C6-membered rings.

We present the systematic exploration of various potential energy surfaces for systems with C6H6-x (x = 0, 1, 2, or 3) empirical formula using an automatic search approach. The primary objective of this study is to identify reaction pathways that lead to the creation of benzene, o-benzyne, and other rings. These pathways initiate with a barrierless recombination reaction and involve subsequent isomerization reactions with submerged transition states until the final product is reached. The reported reaction profiles are consistent with the existing conditions in the interstellar medium if the hot complex formed can cool down through radiative relaxation. Recent studies on the deactivation of polyaromatic hydrocarbons (PAHs) support the possibility of these reactions taking place. The C6-membered rings are considered precursors of PAHs, and our focus is on identifying pathways originating from the barrierless recombination of reactive molecules known to exist in the interstellar medium, with potential implications in other environments.

Exploring Corymbia torelliana hydrochar combustion kinetics through thermogravimetric analysis, peak deconvolution and reaction profile modelling.

This study aims to conduct an applied and innovative investigation to enhance the energy quality of wood residues through hydrothermal carbonization pretreatment. For this purpose, the treatment was carried out at three different temperatures: 180, 220, and 240°C under autogenous pressure. The in natura material and the hydrochars were characterized, and thermogravimetric analyses were performed in an O2 atmosphere with heating rates of 2.5, 5, 10, and 20°Cmin-1. The global activation energy for natura biomass combustion was determined to be 112.49kJ.mol-1. On the other hand, the hydrothermal carbonization process promoted a reduction in this value for the 94.85kJ.mol-1. The conversion function for the in natura biomass was characterized as , order 1, while the hydrochars was 2(1-α) [-ln(1-α)] (1⁄2), Avrami-Erofe'ev I. Triple kinetic parameters were ascertained, and the conversion curves along with their respective derivatives were modeled, exhibiting minimal deviations between theoretical and experimental data. This facilitated the mathematical representation of the reaction processes and allowed for a comprehensive comparison of the results.

Quantum Chemical Characterization of Rotamerism in Thio-Michael Additions for Targeted Covalent Inhibitors.

Myotonic dystrophy type I (DM1) is the most common form of adult muscular dystrophy and is a severe condition with no treatment currently available. Recently, small-molecule ligands have been developed as targeted covalent inhibitors that have some selectivity for and covalently inhibit cyclin-dependent kinase 12 (CDK12). CDK12 is involved in the transcription of elongated RNA sections that results in the DM1 condition. The covalent bond is achieved after nucleophilic addition to a Michael acceptor warhead. Previous studies of the conformational preferences of thio-Michael additions have focused on characterizing the reaction profile based on the distance between the sulfur and β-carbon atoms. Rotamerism, however, has not been investigated extensively. Here, we use high-level quantum chemistry calculations, up to coupled cluster with single, double, and perturbative triple excitations [CCSD(T)], to characterize the nucleophilic addition of an archetypal nucleophile, methanethiolate, to various nitrogen-containing Michael acceptors which are representative of the small-molecule covalent inhibitors. By investigating the structural, energetic, and electronic properties of the resulting enolates, as well as their reaction profiles, we show that synclinal additions are generally energetically favored over other additions due to the greater magnitude of attractive noncovalent interactions permitted by the conformation. The calculated transition states associated with the addition process indicate that synclinal addition proceeds via lower energetic barriers than antiperiplanar addition and is the preferred reaction pathway.

A comparative study on the slow pyrolysis of Miscanthus (Miscanthus×giganteus Greef et Deu.) cultivated on agricultural and contaminated soils: Assessment of distribution of final products

This study aims to investigate the slow pyrolysis behavior of uncontaminated (MSC-I - reference) and heavy metals contaminated (MSC-R) samples with heavy metals from the tailings of a Pb-Zn-Cu flotation mine, consisting of whole stems of Miscanthus. Physicochemical properties of raw materials were investigated through instrumental characterization techniques (Atomic Absorption Spectrometry (AAS), Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, and X-ray diffraction (XRD)), while the pyrolysis process was monitored by simultaneous thermal analysis techniques (thermogravimetry (TG) – derivative thermogravimetry (DTG)), coupled with Mass spectrometry (MS), for evolved gas analysis. After determination of the lignocellulose content (cellulose, hemicellulose, and lignin) and extractive of the MSC-I and MSC-R samples, it was found that Pb, Zn, Fe, and Mn in MSC-R lead to very fast decomposition of extractive fraction, which facilitates their distribution in formed bio-char, together with lignin char-participation, acting catalytically. It was established that a much greater fraction of extractives decomposition products and non-volatile heavy metals are incorporated in MSC-R bio-char increasing its yield (23 %), compared to MSC-I bio-char yield (21.5 %). It was identified that MSC-R has increased production of H2, CO, and CO2, while decreased production of CH4, influenced by Fe (Fe has a significant positive effect on CO2 evaluation during MSC-R pyrolysis, enhancing decarboxylation process). It was established that CH4 reforming reactions catalyzed by iron additionally affect methane reduction, and increase production of H2, compared to the reference sample. Isoconversional kinetic analysis showed that pyrolysis reactions profile was strongly conditioned by the presence of heavy metals, such as Cd, Pb, and Zn, because they affect the modification of biomass lignocellulosic structure. Also, it was found that small amounts of Cd present in MSC-R can increase pyrolysis activation energy of three pseudo-components, and inhibit their deoxygenation, thus increasing yield of bio-char.

Synthesis of 2-Amino-2-deoxy Sugars via Boron-Catalyzed Coupling of Glycosyl Fluorides and Silyl Ether Acceptors.

Although aminosugars are important components in a variety of bioactive molecules, their stereoselective formation is made challenging by the Lewis basic nature of amino substituents. Additionally, the use of N-acyl protecting groups is often problematic due to the competing formation of oxazolines during the glycosylation of 2-aminosugar derivatives. Herein, we report a boron-catalyzed strategy utilizing silyl ether glycosyl acceptors and 2-aminosugar donors that employs the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group for the C2 amino functionality in glycosyl fluorides. This modification allows for operationally simple room-temperature glycosylations and features a rapid reaction profile that addresses some of the limitations in the synthesis of 2-amino-2-deoxy sugar-containing glycosides. Tailoring the order of reactivity of the silyl acceptors enables one-pot iterative glycosylations, thus streamlining the synthesis of complex oligosaccharides while allowing fewer intermediates and purification steps.

Francisella sciaenopsi sp. nov. isolated from diseased red drum Sciaenops ocellatus in Florida, USA.

Piscine francisellosis is one of the most important bacterial diseases affecting various fish species worldwide. Francisella orientalis, F. noatunensis, and F. salimarina (F. marina) have been reported as etiological agents of disease in fish. A Francisella sp. was isolated from several diseased red drum Sciaenops ocellatus experiencing morbidity in Florida, USA, in 2008. In this study, molecular and phenotypic characterization of the recovered isolate was conducted. Phenotypically, the isolate showed a biochemical reaction profile distinct from that of F. orientalis and F. salimarina. Although the 16S rRNA sequence of this isolate shared 99.61% identity to the type strain of F. philomiragia O#319LT, whole genome analysis (average nucleotide identity <95%; digital DNA-DNA hybridization <70%) and a multilocus sequence analysis of 8 concatenated housekeeping genes in comparison with other Francisella spp. indicated that this isolate was a novel Francisella species, more closely related to F. orientalis. Immersion, intracoelomic injection, and co-habitation challenges using a Nile tilapia Oreochromis niloticus fingerling model of infection were done to investigate virulence in a piscine model. Variably pigmented granulomas and pigmented macrophage aggregates were observed in the kidneys and spleens of the challenged fish, but no mortality was recorded during the 15 d challenge period, suggesting that this novel Francisella sp. might be an opportunistic pathogen of fish. Based on the phenotypic and genotypic differences from other Francisella spp. observed in this study, we propose the name Francisella sciaenopsi sp. nov. for this novel isolate.

Family-level profiles of parental reactions to emotions: Longitudinal associations with multi-informant reports of adolescent internalizing and externalizing symptoms.

Longitudinal study of associations between family-level emotion socialization and adolescent adjustment is limited. When American children (53.5% girls) were in second grade (N = 213; Mage = 7.98; data collected 2002-2003), mothers and fathers (79.8% of mothers and 74.2% of fathers were White) reported on their reactions to children's emotions; in seventh, eighth, and ninth grade (Mage = 13.03, 14.17, 15.29, respectively; data collected 2007-2010), adolescents, mothers, and fathers reported on adolescent internalizing and externalizing symptoms. Four family-level profiles of reactions were identified. Profile differences emerged, suggesting that the emotion dismissing profile was longitudinally associated with elevated adolescent internalizing and externalizing symptoms and that fathering may especially foster child adjustment for families in a divergence profile.

Micelle Enabled Buchwald‐Hartwig Amination in Water with the Bening by Design Surfactant TPGS‐750‐M for the Synthesis of the JAK Inhibitor 4‐((2‐Chlorophenyl)amino)‐6‐((6‐methylpyridin‐2‐yl)amino)nicotinamide

AbstractAn efficient and scalable Buchwald‐Hartwig amination towards the synthesis of the API candidate 4‐((2‐Chlorophenyl)amino)‐6‐((6‐methylpyridin‐2‐yl)amino)nicotinamide as a JAK inhibitor was described. The process was developed using water and a water‐miscible co‐solvent. It was facilitated by the benign by design surfactant TPGS‐750‐M, that promoted the robust and reliable preparation of our target compound in high yields, with improved reaction profile and via an operationally simple protocol.

Homogeneous Zn(II) salts as efficient Lewis acid catalysts for the esterification of levulinic acid with diols

The valorization of renewable feedstocks to produce biochemicals and biofuels is an essential focus of contemporary research, with non-food crop biomass emerging as a cost-effective and environmentally friendly option. Among the chemicals derived from lignocellulosic biomass, levulinic acid (LAH) is a notable chemical platform due to its versatile applications. This study investigates the eco-friendly esterification of levulinic acid with polyols, catalyzed by zinc(II) species under mild, solvent-free conditions.A comprehensive screening of various zinc(II) species was conducted, to identify the most effective catalyst, ultimately selecting zinc triflate for its performance. The esterification scope was extended to three diols: 1,4-butanediol, 1,6-hexanediol, and 1,8-octanediol. These esters can replace fossil-based chemicals in many emerging sectors, as lubricants and as components in energy storage devices. The reaction conditions were fine-tuned to maximize yield and selectivity, using NMR spectroscopy to monitor the formation of mono- and di-esters and assess reaction profiles. Optimization experiments demonstrated that a catalyst loading of 1.0 %mol and a temperature of 120 °C yielded quantitative conversion within convenient reaction time (2–4 h). The findings highlight the efficiency of simple zinc(II) catalysts in producing levulinate esters with high yields and selectivity under sustainable conditions. Therefore, this research contributes to the development of greener processes to produce valuable chemicals and additives from renewable resources.

A Possible Additional Formation Pathway for the Interstellar Diatomic SiS

The formation of silicon monosulfide (SiS) in space appears to be a difficult process, but the present work shows that a previously excluded pathway may contribute to its astronomical abundance. Reaction of the radicals SH + SiH produces SiS with a submerged transition state and generates a stabilizing H2 molecule as a product to dissipate the kinetic energy. Such is a textbook chemical reaction for favorable gas-phase chemistry. While previously proposed mechanisms reacting atomic sulfur and silicon with SiH, SH, and H2S will still be major contributors to the production of SiS, an abundance of SiS in certain regions could be a marker for the presence of SiH where it has previously been unobserved. These quantum chemically computed reaction profiles imply that the silicon-chalcogen chemistry of molecular clouds, shocked regions, or protoplanetary disks may be richer than previously thought. Quantum chemical spectral data for the intermediate cis- and trans-HSiSH are also provided to aid in their potential spectroscopic characterization.

A real-world data analysis of ocular adverse events linked to anti-VEGF drugs: a WHO-VigiAccess study.

Vascular endothelial growth factor (VEGF) is key to wet age-related macular degeneration (wAMD). Anti-VEGF drugs are the main treatment in clinics. This study assessed ocular adverse events (AE) from anti-VEGF drugs in VigiAccess, WHO's database, and compared adverse drug reaction (ADR) profiles of four drugs to aid personalized treatment choices for optimal benefit and safety. The design was a descriptive retrospective study. We observed four anti-VEGF drugs commonly used in the clinical treatment of wAMD, and their ADR reports came from WHO-VigiAccess. The collected data included the age group, gender, and regional data, as well as the data of disease systems and symptoms caused by ADR recorded in the annual ADR reports and reports received by the WHO. We observed the overall characteristics of the ADR reports of these drugs, then explored the distribution of 27 SOCs of these drugs. Subsequently, we compared the most common ocular ADRs of the drugs. Finally, we compared the commonalities and differences of ocular ADRs related to the drugs. Overall, 57,779 AE associated with the four anti-VEGF drugs were reported. The results showed that the number of females experiencing ADRs (67.83%) was significantly higher than males (32.17%), the age group with the highest reported incidence was over 75years old. More than half of the ADR reports came from the Americas (50.86%). The five most common types of AE were: eye disorders (43.56%), general disorders and administration site conditions (34.47%), injury poisoning and procedural complications (13.36%), infections and infestations (11.61%), nervous system disorders (9.99%). Compared with the other three inhibitors, brolucizumab had a significantly higher rate of ocular ADR reports. The most common ocular ADRs of these four anti-VEGF drugs were mostly related to visual impairment, vision blurred, and blindness. However, there is still a disparity of ADRs between different drugs. The presence of ocular AEs when using anti-VEGF drugs to treat wAMD in clinical practice should attract clinical attention. Clinicians should use these expensive drugs more rationally based on the characteristics of ADRs and develop personalized treatment plans for patients.