Multifunctional Molecule Research Articles

Understanding the fragmentation of glucose in mass spectrometry.

The fragmentation mechanism of D-glucose was investigated in detail by two different fragmentation techniques, namely, collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) using all six 13 C-labeled isotopomers and 2 H-labeled isotopomers. For both CID and IRMPD energy-resolved measurements were carried out. Individual fragmentation pathways were studied at MS2 and MS3 levels. Additionally, we have developed an HPLC-tandem MS method to separate the anomers of D-glucose using a HILIC column and investigated their fragmentation patterns individually. We propose a complete fragmentation landscape of D-glucose, demonstrating that a rather simple multifunctional molecule displays extreme complexity in gas phase dissociation, following multiple parallel fragmentation routes yielding a total of 23 distinct fragment ions. The results allowed a detailed formulation of the complex fragmentation mechanism of D-glucose. The results have immediate consequences for the full structure analysis of complex carbohydrates.

Melatonin in plants: A pleiotropic molecule for abiotic stresses and pathogens infection

Melatonin is a pleiotropic molecule with diverse physiological effects in plants. Pleiotropy refers to a single molecule's ability to produce multiple effects within an organism, making it a multifunctional molecule that can influence various physiological processes simultaneously. In this review, we focus on exploring Melatonin's role in potato plants, specifically examining the evidence supporting its involvement in abiotic stress responses and defense against pathogen infection. Previous studies have demonstrated that Melatonin plays a crucial role in regulating abiotic stress responses in potato plants. It acts as an effective antioxidant, safeguarding the plant against oxidative stress induced by high salinity and drought. Melatonin mitigates the detrimental impacts of chilling stress, cold shock, and frost damage, thereby enhancing the potato plants' tolerance to ultraviolet radiation. Melatonin exhibits significant involvement in protecting potato plants against pathogen infection. It acts as an inducer of defense responses, triggering the production of defense compounds in potato plants. Melatonin displays antifungal properties, effectively inhibiting the growth of various fungal pathogens. This review emphasizes the pleiotropic nature of Melatonin in potato plants, particularly in relation to abiotic stress responses and defense against pathogen infection. Future research should focus on elucidating the underlying mechanisms by which Melatonin safeguards potato plants from these stressors, as well as exploring the roles of other molecules involved in this process. Furthermore, it is essential to investigate the effects of Melatonin in other plant species to determine the breadth of its biological activities. Overall, by comprehending the multifaceted functions of Melatonin in potato plants, we can enhance our understanding of plant physiology and potentially develop strategies for improving stress tolerance and disease resistance in horticultural crops.

Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development, disease diagnosis, and basic theoretical research. Aminopeptidase N (APN), as a representative tumor biomarker with anti-tumor potential, still lacks a high-precision theranostic probe specifically targeting it. In this study, a novel quaternity design strategy for APN theranostic probe was developed. This proposed strategy utilizes advanced machine learning and molecular dynamics simulations, and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments. Through this strategy, a unique “Off–On” theranostic probe, ABTP-DPTB, was ingeniously constructed to light up APN through fluorescence restoration, relying on conformation-induced effects and solvent restriction. Differ from the common diagnostic probes, the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ imaging. The fabricated probe was used for detecting and inhibiting APN in various environments, with a better in vitro inhibitory than golden-standard drug bestatin.

Refining interface compatibility and carrier management via π-π conjugated stacking for efficient and stable perovskite solar cells based on low-temperature processing

ABSTRACT Deficiencies and instability in the ETL, perovskite layer, or their interface contribute to carrier nonradiative recombination losses. To address these issues, we propose an electron collection and injection optimisation strategy that focuses on enhancing the compatibility and charge transfer performance at the ETL-perovskite interface. Our approach involves low-temperature modification TiO2 with pyrimidine-2-carboximidamide acetate (PCA) through π-π stacking, reducing the surface energy and improving the interfacial compatibility. At the same time, a stable organic–inorganic hybrid layer is formed with lead iodide (PbI2) below the perovskite layer. Additionally, we demonstrate long-term ambient stability, with the PSCs retaining approximately 90% of their initial PCE after 100 days. We also fabricate large-area modules, achieving an efficiency of 19.53% with an active area of 36.41 cm2. Highlights The introduction of the π-π stacking multifunctional molecule PCA through a low-temperature process to modify TiO2 film enhances the stability and performance of perovskite solar cells. This novel approach improves interfacial compatibility and reduces defects at the interface, enabling vertically aligned crystal growth of perovskite and increasing the interfacial contact area. By effectively removing two types of Hydroxyl groups over the low-temperature TiO2 film through multiple surface chemical reactions, the strategy mitigates nonradiative recombination, leading to reduced energy losses and improved performance in both small and large-area perovskite solar cell modules.

Plant Hormone Signals Mediate Melatonin Synthesis to Enhance Osmotic Stress Tolerance in Watermelon Cells

Melatonin, a multifunctional signaling molecule, has been shown to play a significant role in response to abiotic stress. Several species have been reported to unveil melatonin’s effect on osmotic stress; however, the signal transduction mechanism of phytohormone-mediated melatonin biosynthesis in plant species remains unclear. In this study, although plants can biosynthesize melatonin, the exogenous application of melatonin to watermelon cells can improve cell growth in response to osmotic stress by regulating the antioxidant machinery of cells. Regarding the melatonin synthesis pathway, ClOMT (ClASMT and ClCOMT) is a multi-gene family, and ClSNAT has two members. Both ClOMTs and ClSNATs harbor the cis-elements in their promoter regions responding to various hormones. Among abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA), ABA treatment observably upregulated the expression of ClOMTs and ClSNATs, and the accumulation of melatonin with ABA treatment reached a level comparable to that with osmotic stress by mannitol treatment. Furthermore, when hormone biosynthesis inhibitors were added to cells before osmotic stress, the expression of ClOMTs and ClSNATs, as well as melatonin accumulation, were significantly suppressed with the ABA biosynthesis inhibitor. This study demonstrated the crucial role of melatonin biosynthesis in response to osmotic stress via plant hormone signal transduction. It showed that ABA signaling plays a dominant role in melatonin synthesis under osmotic stress.

Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma.

Glioma is regarded as a prevalent form of cancer that affects the Central Nervous System (CNS), with an aggressive growth pattern and a low clinical cure rate. Despite the advancement of the treatment strategy of surgical resection, chemoradiotherapy and immunotherapy in the last decade, the clinical outcome is still grim, which is ascribed to the low immunogenicity and tumor microenvironment (TME) of glioma. The multifunctional molecule, called ceruloplasmin (CP) is involved in iron metabolism. Its expression pattern, prognostic significance, and association with the immune cells in gliomas have not been thoroughly investigated. Studies using a variety of databases, including Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gliovis, showed that the mRNA and protein expression levels of CP in patients suffering from glioma increased significantly with an increasing glioma grade. Kaplan-Meier (KM) curves and statistical tests highlighted a significant reduction in survival time of patients with elevated CP expression levels. According to Cox regression analysis, CP can be utilized as a stand-alone predictive biomarker in patients suffering from glioma. A significant association between CP expression and numerous immune-related pathways was found after analyzing the data using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses indicated a substantial correlation between the CP expression and infiltration of immunocytes in the TME. Additionally, immune checkpoints and CP expression in gliomas showed a favorable correlation. According to these results, patients with glioma have better prognoses and levels of tumor immune cell infiltration when their CP expression is low. As a result, CP could be used as a probable therapeutic target for gliomas and potentially anticipate the effectiveness of immunotherapy.

Synergistic Ion-Anchoring Passivation for Perovskite Solar Cells with Efficiency Exceeding 24% and Ultra-Ambient Stability.

The high-density defect states existing at the grain boundaries and heterojunction interfaces induce nonradiative charge recombination and ion migration processes within perovskite film, which seriously impair the device efficiency and stability. Here, we propose a novel synergistic ion-anchoring passivation (SIP) strategy for high-performance perovskite solar cells, by designing a multifunctional molecule to heal the charged defects via electrostatic interactions. The anion and cation species of the multifunctional molecule are rationally screened via high-throughput DFT simulation and experimental verification, which act as efficient surface passivation agents to heal the lead- and iodine-related defects. As a result, the defect-less perovskite films deliver encouraging device power conversion efficiency >24% with negligible hysteresis. A remarkable open-circuit voltage (Voc) of 1.17 V was obtained with a Voc deficit of 370 mV, featuring the outstanding defect-passivation capability of the SIP strategy. Moreover, the SIP-treated devices show exceptional ambient stability and maintain 70% of the initial efficiency after 150 h of high humidity exposure (relative humidity 70%-80%). Our results highlight the importance of the rational design of passivation agents to realize high-performance perovskite electronics.

Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer's Disease Cell Model.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. β-amyloid1-42 (Aβ1-42) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aβ aggregation and rescuing memory and learning deficit through the NO signaling pathway. Targeting the NO pathway might be a therapeutic option; however, NO has a limited half-life under the biological system. To address this issue, a biomimetic dinitrosyl iron complex [(NO)2Fe(μ-SCH2CH2COOH)2Fe(NO)2] (DNIC-COOH) that could stably deliver NO was explored in the current study. To determine whether DNIC-COOH exerts anti-AD efficacy, DNIC-COOH was added to neuron-like cells and primary cortical neurons along with Aβ1-42. This study found that DNIC-COOH protected neuronal cells from Aβ-induced cytotoxicity, potentiated neuronal functions, and facilitated Aβ1-42 degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.

Atmospheric oxidation of (E)-β-farnesene initiated by hydroxyl radical: New formation mechanism of HOMs

(E)-β-farnesene is one of the acyclic sesquiterpenes, whose atmospheric oxidation has been determined as a significant contributor to SOA formation due to the formed highly oxidized multifunctional molecules (HOMs). In this work, the atmospheric oxidation of (E)-β-farnesene initiated by OH radical was comprehensively investigated using quantum chemical calculation. For the initial reactions, OH addition reactions are dominant over H atom abstraction reactions because of lower free energy barriers. The first-generation products involving acetone, (E)− 4-methyl-8-methylenedeca-4,9-dienal, 4-methylenehex-5-enal (P3), 6-methylhept-5-en-2-one (P4), formaldehyde, (E)− 7,11-dimethyldodeca-1,6,10-trien-3-one and (E)− 6,10-dimethyl-2-methyleneundeca-5,9-dienal are produced from the subsequent reactions of the OH-(E)-β-farnesene adducts with NO and HO2. The second-generation products, such as 4-oxopentanal, 4-methylenehex-5-enal, (E)− 4-methyl-8-oxodeca-4,9-dienal, formaldehyde and (E)− 4-methyl-8-methylenenon-4-enedial, are also determined from the successive oxidations of P2 and P3 under high and low NOx conditions. For the formation of HOMs, the H atom shift is the bottleneck for the autooxidation mechanism while our newly proposed mechanism, i.e. the multiple H abstractions by OH radical and reactions with O2 and HO2, is a more thermodynamically favorable formation pathway of the HOMs. Due to the intricate oxidation mechanisms and products, it is difficult to comprise the oxidation mechanisms of sesquiterpenes (including (E)-β-farnesene) in the atmospheric chemical models to thoroughly evaluate their contributions to SOA formation. We expect that this comprehensive oxidation mechanism of (E)-β-farnesene from a theoretical perspective would be conducive to clarifying the atmospheric fate of (E)-β-farnesene and even sesquiterpenes.

Severe udder cleft dermatitis lesion transcriptomics points to an impaired skin barrier, defective wound repair and a dysregulated inflammatory response as key elements in the pathogenesis.

This study is the first to investigate the transcriptomic changes occurring in severe udder cleft dermatitis lesions (UCD) in Holstein-Friesian cows. An examination of the gene expression levels in natural UCD lesions and healthy udder skin through RNA Seq-Technology provided a deeper insight into the inflammatory pathways associated with this disease. A clear distinction between the gene expression patterns of UCD lesions and healthy skin was shown in the principal component analysis. Genes coding for inflammatory molecules were upregulated such as the chemokines C-X-C motif ligand 2 (CXCL2), 5 (CXCL5) and 8 (CXCL8), and C-C motif ligand 11 (CCL11). Moreover, the genes coding for the multifunctional molecules ADAM12 and SLPI were amongst the highest upregulated ones, whereas the most downregulated genes included the ones coding for keratins and keratin-associated molecules. Predominantly inflammatory pathways such as the chemokine signaling, cytokine receptor interaction and IL-17 signaling pathway were significantly upregulated in the pathway analysis. These results point towards a fulminant, dysregulated inflammatory response concomitant with a disruption of the skin barrier integrity and a hampered wound repair mechanism in severe UCD lesions.

Modulating Crystallization and Defect Passivation by Butyrolactone Molecule for Perovskite Solar Cells.

The attainment of a well-crystallized photo-absorbing layer with minimal defects is crucial for achieving high photovoltaic performance in polycrystalline solar cells. However, in the case of perovskite solar cells (PSCs), precise control over crystallization and elemental distribution through solution processing remains a challenge. In this study, we propose the use of a multifunctional molecule, α-amino-γ-butyrolactone (ABL), as a modulator to simultaneously enhance crystallization and passivate defects, thereby improving film quality and deactivating nonradiative recombination centers in the perovskite absorber. The Lewis base groups present in ABL facilitate nucleation, leading to enhanced crystallinity, while also retarding crystallization. Additionally, ABL effectively passivates Pb2+ dangling bonds, which are major deep-level defects in perovskite films. This passivation process reduces recombination losses, promotes carrier transfer and extraction, and further improves efficiency. Consequently, the PSCs incorporating the ABL additive exhibit an increase in conversion efficiency from 18.30% to 20.36%, along with improved long-term environmental stability. We believe that this research will contribute to the design of additive molecular structures and the engineering of components in perovskite precursor colloids.

Passivating SnO2/perovskite interface via guanide hydrochloride toward efficient and stable n-i-p perovskite solar cells

Nonradiation recombination of interfacial carriers is a key factor hindering the improvement of efficiency and stability of perovskite solar cells (PSCs). Here, we report an effective electron transport layer/perovskite interface regulation strategy. By introducing the multifunctional molecule guanidine hydrochloride (GCl) on the surface of SnO2, we can enhance the electron extraction between SnO2 and perovskite and promote the growth of high-quality perovskite films. GCl is anchored on the surface of SnO2 and interacts with undercoordinated ions in perovskite. The experimental results show that GCl has interaction with both SnO2 and perovskite layer, and a “bridge” connection is formed between the two layers. This strategy not only passivates the SnO2/perovskite interface defects, improves the perovskite crystallization quality, but also helps to reduce the interface charge accumulation. More importantly, the PCE of GCl passivated device reached 21.63 %, which was much better than that of control device (19.56 %). In the air environment, after 30 days at room temperature, the GCl modified unpackaged device maintained 83 % of its initial efficiency. Therefore, interface modification with GCl is an effective strategy to improve the interface state, improve the crystallization quality and obtain high-performance PSCs.

Potential roles of melatonin in mitigating the heavy metals toxicity in horticultural plants

Heavy metals (HMs) pollution is one of the most important environmental and agricultural soil challenges, and it is mostly caused by anthropogenic activities. International agricultural and environmental research focuses on decreasing HMs toxicity from soils of farmland, and mitigating HMs phytotoxicity. Melatonin (MT), being a multifunctional molecule, has strong antioxidant properties and is widely used to alleviate abiotic stresses particularly HMs. MT, a newly discovered signaling molecule and plant growth regulator, is essential for plants to be resistant towards abiotic stress. Present research indicates that MT is useful in reducing the toxic effects of HMs in horticultural crop, offering a fresh strategy to reduce HMs contamination in horticultural plants. This review highlights studies investigating the function of MT in reducing HMs toxicity in horticultural plants as well as related physiological and environmental mechanisms, such as lowering HMs accumulation in the rhizosphere, resolving and isolating HMs locally, sustaining mineral nutrient content, boosting antioxidant defense mechanisms, and actively engaging with hormonal signaling. The objective this of this review is theoretical framework for managing the accumulation of HMs ions in horticultural plants cultivated in polluted soil.

Discovery of dual PARP and CDK6 inhibitors for triple-negative breast cancer with wild-type BRCA

Inhibition of PARP is synthetic lethal with defects in BRCA, which provide effective targeted therapy strategy for BRCA mutation type of TNBC patients. However, approximately 80% of TNBC patients do not have BRCA mutations. Recent studies have shown that CDK4/6 inhibitors can increase the sensitivity of wild-type BRCA cells to PARP inhibitors. We designed a series of dual PARP and CDK6 inhibitors, and the most promising compound, P4i, showed good inhibitory activity against PARP1 and CDK6 and good inhibitory effects on MDA-MB-231 (IC50 = 1.96 μM), MDA-MB-468 (IC50 = 2.81 μM) and BT-549 (IC50 = 2.37 μM) cells with wild-type BRCA. Compared with Olaparib, the inhibition capacity of the three BRCA wild-type (MDA-MB-231, MDA-MB-468 and BT-549) cells was about 10–20 times higher, and even better than the combination of Olaparib and Palbociclib. As a novel PARP multifunctional molecule, it is a potential compound for the treatment of BRCA wild-type TNBC.

Design, synthesis, and evaluation of new anti-inflammatory natural products amide derivatives endowed with anti-blood cancer activity towards development of potential multifunctional agents against hematological cancers

New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed as multifunctional antiproliferative molecules against blood cancer and the associated inflammatory conditions. The targeted compounds were synthesized efficiently in three linear steps employing known chalcone starting materials. Compounds 2h, 2i, 2l, 2t, 2v and 2x having bromo or nitro substituted-phenyl rings elicited potential inhibitory effects on macrophages production of nitric oxide, PGE2 and TNF-α which are proinflammatory mediators involved in tumorigenesis and progression of blood cancer. Additionally, evaluation of direct inhibitory effects on the growth of diverse blood cancers including leukemia, lymphoma, and myeloma cell lines unveiled compound 2v as the most potential molecules eliciting at least five-folds the potency of the standard imatinib drug over the used diverse blood cancers. Furthermore, compound 2v showed good selectivity to blood cancer cells rather than normal MRC5 cells. Moreover, compound 2v triggered death of HL60 leukemia cells via apoptosis induction. In conclusion, the natural product-derived compound 2v might serve as a multifunctional lead compound for further development of agents for treatment of blood cancers.

Phenylboronic Ester-Bridged Chitosan/Myricetin Nanomicelle for Penetrating the Endothelial Barrier and Regulating Macrophage Polarization and Inflammation against Ischemic Diseases.

The brain and liver are more susceptible to ischemia and reperfusion (IR) injury (IRI), which triggers the reactive oxygen species (ROS) burst and inflammatory cascade and results in severe neuronal damage or hepatic injury. Moreover, the damaged endothelial barrier contributes to proinflammatory activity and limits the delivery of therapeutic agents such as some macromolecules and nanomedicine despite the integrity being disrupted after IRI. Herein, we constructed a phenylboronic-decorated chitosan-based nanoplatform to deliver myricetin, a multifunctional polyphenol molecule for the treatment of cerebral and hepatic ischemia. The chitosan-based nanostructures are widely studied cationic carriers for endothelium penetration such as the blood-brain barrier (BBB) and sinusoidal endothelial barrier (SEB). The phenylboronic ester was chosen as the ROS-responsive bridging segment for conjugation and selective release of myricetin molecules, which meanwhile scavenged the overexpressed ROS in the inflammatory environment. The released myricetin molecules fulfill a variety of roles including antioxidation through multiple phenolic hydroxyl groups, inhibition of the inflammatory cascade by regulation of the macrophage polarization from M1 to M2, and endothelial injury repairment. Taken together, our present study provides valuable insight into the development of efficient antioxidant and anti-inflammatory platforms for potential application against ischemic disease.

Steering the Surface-Confined Self-Assembly of Multifunctional Star-Shaped Molecules

Steering the Surface-Confined Self-Assembly of Multifunctional Star-Shaped Molecules

Hydrogen sulfide alleviates chromium toxicity by promoting chromium sequestration and re-establishing redox homeostasis in Zea mays L

Hydrogen sulfide (H2S) is a multifunctional gaseous signaling molecule involved in the regulation of Cr stress responses. In the present study, we combined transcriptomic and physiological analyses to elucidate the mechanism underlying the mitigation of Cr toxicity by H2S in maize (Zea mays L.). We showed that treatment with sodium hydrosulfide (NaHS, a donor of H2S) partially alleviated Cr-induced growth inhibition. However, Cr uptake was not affected. RNA sequencing suggested that H2S regulates the expression of many genes involved in pectin biosynthesis, glutathione metabolism, and redox homeostasis. Under Cr stress, NaHS treatment significantly increased pectin content and pectin methylesterase activity; thus, more Cr was retained in the cell wall. NaHS application also increased the content of glutathione and phytochelatin, which chelate Cr and transport it into vacuoles for sequestration. Furthermore, NaHS treatment mitigated Cr-induced oxidative stress by enhancing the capacity of enzymatic and non-enzymatic antioxidants. Overall, our results strongly support that H2S alleviates Cr toxicity in maize by promoting Cr sequestration and re-establishing redox homeostasis rather than by reducing Cr uptake from the environment.

MicroRNA in Alzheimer’s Disease: Results of interaction analysis

AbstractBackgroundMiRNA are multifunctional molecules involved in regulating posttranscriptional expression of genes. Several studies showed that miR‐107 influences expression of the BACE1 gene in the process of Aβ production. Extracellular accumulation of Aβ is well‐known hallmark of Alzheimer’s disease (AD). The product NLRP3 gene is involved in inflammasome that induces neuroinflammation a pathological process accompanying AD. The role of miR‐107 in regulation of NRLP3 is unknown.MethodWe used logistic regression model with the interaction term to test the hypothesis that interaction of SNPs from miR‐107 with SNPs from the NLRP3 gene is associated with AD. For this we used data on genotyped individuals collected in Framingham Health Study (FHS). The Cardiovascular Health Study (CHS) was used to replicate the research findings. Linkage Disequilibrium test and clumping procedure were used to reduce the number of tests and make Bonferroni correction less conservative.ResultIn the analysis of FHS data we found that the association of the rs2926616 SNP from the miR‐107 miRNA with the rs10754557 SNP from the NLRP3 gene is positive and statistically significant. The effect size β = 0.356, p‐value 6.71E‐03. This value is smaller than the p‐value threshold calculated in accordance with Bonferroni correction 7.14E‐03. This result is replicated in the analysis of CHS data with β = 0.289, and p‐value 4.76E‐02. Using FHS data we also tested the role of interaction of SNPs from the miR‐107 with SNPs from the TLR2 gene in AD and found a pair of SNPs whose interaction has statistically significant association with AD. This finding was replicated in the analysis of the CHS data where an interaction of a pair of SNPs also showed significant association with AD. Detected SNPs from this pair were in linkage disequilibrium with the pair SNPs from the CHS data.ConclusionThe results of these analyses indicate that one miRNA may influence several components of AD pathological development. This property may have important implications for developing efficient medications against AD. More studies are needed to evaluate miRNA involvement in different pathways of AD regulation, as well as in identifying factors capable in affecting such miRNA.

Buried modification with tetramethylammonium chloride to enhance the performance of perovskite solar cells with n-i-p structure

Intrinsic defects in the electron transport layer (ETL) and perovskite (PVK) layer, as well as energy level mismatch between the PVK and ETL, severely limit the device performance of perovskite solar cells (PSCs). Here, we introduced a multifunctional molecule (tetramethylammonium chloride, TMACl) as a passivator in the SnO2 ETL. During the annealing treatment, the defects in SnO2 ETL are suppressed by passivating the oxygen vacancies on the surface of SnO2. Moreover, the presence of TMACl enables the defects inevitably generated during the annealing process of PVK to be effectively passivated by the migrating TMA+ cations and Cl− anions. The characterization results further confirm that the surface modification of TMACl is more favorable for the suppression of interfacial recombination and the passivation of bulk and grain boundary defects of PVK compared to the bulk doping method. It is noteworthy that, compared with the pristine device (21.02%), the devices based on TMACl-doped SnO2 and TMACl-modified SnO2 ETLs obtained superior champion efficiencies of 22.71% and 23.08%, respectively. More importantly, the unencapsulated PSCs based on TMACl-modified SnO2 maintained 88% of their original efficiency during 35 days of storage in a humidity-controlled chamber with a relative humidity of 20–30%, demonstrating the passivation of SnO2 ETL using TMACl salts is an effective and promising approach to achieving high photovoltaic performances of PSCs.