SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.

Mitochondria are cellular powerhouses that generate energy through the electron transport chain (ETC). The mitochondrial genome (mtDNA) encodes essential ETC proteins in a compartmentalized manner, however, the mechanism underlying metabolic regulation of mtDNA function remains unknown. Here, we report that expression of tricarboxylic acid cycle enzyme succinate-CoA ligase SUCLG1 strongly correlates with ETC genes across various TCGA cancer transcriptomes. Mechanistically, SUCLG1 restricts succinyl-CoA levels to suppress the succinylation of mitochondrial RNA polymerase (POLRMT). Lysine 622 succinylation disrupts the interaction of POLRMT with mtDNA and mitochondrial transcription factors. SUCLG1-mediated POLRMT hyposuccinylation maintains mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation. Specifically, leukemia-promoting FMS-like tyrosine kinase 3 (FLT3) mutations modulate nuclear transcription and upregulate SUCLG1 expression to reduce succinyl-CoA and POLRMT succinylation, resulting in enhanced mitobiogenesis. In line, genetic depletion of POLRMT or SUCLG1 significantly delays disease progression in mouse and humanized leukemia models. Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.

Primary cilia restrict autoinflammation by mediating PD-L1 expression.

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Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Fisetin nanoparticles based on cells cycle and apoptosis intervention for the treatment of lymphoma and leukemia.

Lymphoma and leukemia are both hematological system tumors with complex etiology, and mainly treated with chemotherapeutic drugs. However, therapeutic drugs can interrupt curative effect due to different side effects. Therefore, it is worthwhile to develop a novel therapeutic for providing insights for clinical tumor treatment. In this study, we developed a fisetin nanoparticles (Fisetin NPs) through a self-assembled method, and investigated the activity and potential mechanism of Fisetin NPs against lymphoma and leukemia. The spherical and uniformly distributed Fisetin NPs effectively inhibited both tumor cells proliferation, arrested EL4 cells G0/G1 phase and K562 cells G2/M phase, and induced apoptosis in vitro. In vivo, Fisetin NPs exhibited excellent tumor growth inhibition, effective inhibition of cell proliferation and angiogenesis, significant induction of apoptosis and ideal safety. Mechanically, fisetin upregulated genes (Fas, Pidd, Puma, Apaf1, and p21) in the p53 signaling pathway and bound to N-acetyltransferase 10 (NAT10), ribosomal protein L34 (RPL34) and GTP binding protein 4 (GTPBP4). Collectively, Fisetin NPs have promising therapeutic effects on lymphoma and leukemia, which are of great significant for clinical implications.

FTO ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via P53-P21/Nrf2 activation in a HuR-dependent m6A manner.

Doxorubicin (DOX)-induced cardiotoxicity seriously limits its clinical applicability, and no therapeutic interventions are available. Ferroptosis, an iron-dependent regulated cell death characterised by lipid peroxidation, plays a pivotal role in DOX-induced cardiotoxicity. N6-methyladenosine (m6A) methylation is the most frequent type of RNA modification and involved in DOX-induced ferroptosis, however, its underlying mechanism remains unclear. P21 was recently found to inhibit ferroptosis by interacting with Nrf2 and is regulated in a P53-dependent or independent manner, such as through m6A modification. In the present study, we investigated the mechanism underlying m6A modification in DOX-induced ferroptosis by focusing on P21. Our results show that fat mass and obesity-associated protein (FTO) down-regulation was associated with DOX-induced cardiotoxicity. FTO over-expression significantly improved cardiac function and cell viability in DOX-treated mouse hearts and H9C2 cells. FTO over-expression significantly inhibited DOX-induced ferroptosis, and the Fer-1 inhibition of ferroptosis significantly reduced DOX-induced cardiotoxicity. P21 was significantly upregulated by FTO and activated Nrf2, playing a crucial role in the anti-ferroptotic effect. FTO upregulated P21/Nrf2 in a P53-dependent manner by mediating the demethylation of P53 or in a P53-independent manner by mediating P21/Nrf2 directly. Human antigen R (HuR) is crucial for FTO-mediated regulation of ferroptosis and P53-P21/Nrf2. Notably, we also found that P21 inhibition in turn inhibited HuR and P53 expression, while HuR inhibition further inhibited FTO expression. RNA immunoprecipitation assay showed that HuR binds to the transcripts of FTO and itself. Collectively, FTO inhibited DOX-induced ferroptosis via P21/Nrf2 activation by mediating the m6A demethylation of P53 or P21/Nrf2 in a HuR-dependent manner and constituted a positive feedback loop with HuR and P53-P21. Our findings provide novel insight into key functional mechanisms associated with DOX-induced cardiotoxicity and elucidate a possible therapeutic approach.

XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis.

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-ß (TGF-ß), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-ß-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.

Lipid droplets in pathogen infection and host immunity.

As the hub of cellular lipid metabolism, lipid droplets (LDs) have been linked to a variety of biological processes. During pathogen infection, the biogenesis, composition, and functions of LDs are tightly regulated. The accumulation of LDs has been described as a hallmark of pathogen infection and is thought to be driven by pathogens for their own benefit. Recent studies have revealed that LDs and their subsequent lipid mediators contribute to effective immunological responses to pathogen infection by promoting host stress tolerance and reducing toxicity. In this comprehensive review, we delve into the intricate roles of LDs in governing the replication and assembly of a wide spectrum of pathogens within host cells. We also discuss the regulatory function of LDs in host immunity and highlight the potential for targeting LDs for the diagnosis and treatment of infectious diseases.

A review of the application of mesenchymal stem cells in the field of hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for many malignant hematological diseases. Mesenchymal stem cells (MSCs) are nonhematopoietic stem cells with strong self-renewal ability and multidirectional differentiation potential. They have the characteristics of hematopoietic support, immune regulation, tissue repair and regeneration, and homing. Recent studies have shown that HSCT combined with MSC infusion can promote the implantation of hematopoietic stem cells and enhance the reconstruction of hematopoietic function. Researchers have also found that MSCs have good preventive and therapeutic effects on acute and chronic graft-versus-host disease (GVHD), but there is still a lack of validation in large-sample randomized controlled trials. When using MSCs clinically, it is necessary to consider their dose, source, application time, application frequency and other relevant factors, but the specific impact of the above factors on the efficacy of MSCs still needs further clinical trial research. This review introduces the clinical roles of MSCs and summarizes the most recent progress concerning the use of MSCs in the field of HSCT, providing references for the later application of the combination of MSCs and HSCT in hematological diseases.

Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.

Quality-of-life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia.

BACKGROUND: Treatment-free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality-of-life (QoL) and mental health in CML patients with full-dose TKI, low-dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation. METHODS: We conducted a cross-sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation. RESULTS: 1450 responses were included in the analysis. 44.3% of respondents reported a moderate-to-severe impact of TKI treatment on their QoL. 17% of respondents had moderate-to-severe anxiety. 24.4% of respondents had moderate-to-severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long-term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full-dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping. CONCLUSIONS: TKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full-dose treatment to discontinuation. Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality-of-life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full-dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.

Two-Dimensional Pb Square Nets from Bulk (RO)nPb (R = Rare Earth Metals, n = 1,2).

All two-dimensional (2D) materials of group IV elements from Si to Pb are stabilized by carrier doping and interface bonding from substrates except graphene which can be free-standing. The involvement of strong hybrid of bonds, adsorption of exotic atomic species, and the high concentration of crystalline defects are often unavoidable, complicating the measurement of the intrinsic properties. In this work, we report the discovery of seven kinds of hitherto unreported bulk compounds (RO)nPb (R = rare earth metals, n = 1,2), which consist of quasi-2D Pb square nets that are spatially and electronically detached from the [RO]δ+ blocking layers. The band structures of these compounds near Fermi levels are relatively clean and dominantly contributed by Pb, resembling the electron-doped free-standing Pb monolayer. The R2O2Pb compounds are metallic at ambient pressure and become superconductors under high pressures with much enhanced critical fields. In particular, Gd2O2Pb (9.1 µB/Gd) exhibits an interesting bulk response of lattice distortion in conjunction with the emergence of superconductivity and magnetic anomalies at a critical pressure of 10 GPa. Our findings reveal the unexpected facets of 2D Pb sheets that are considerably different from their bulk counterparts and provide an alternative route for exploring 2D properties in bulk materials.

The Bacillus cereus toxin alveolysin disrupts the intestinal epithelial barrier by inducing microtubule disorganization through CFAP100.

Bacillus cereus is a Gram-positive bacterium that mainly causes self-limiting emetic or diarrheal illness but can also cause skin infections and bacteremia. Symptoms of B. cereus ingestion depend on the production of various toxins that target the gastric and intestinal epithelia. From a screen of bacterial isolates from human stool samples that compromised intestinal barrier function in mice, we identified a strain of B. cereus that disrupted tight and adherens junctions in the intestinal epithelium. This activity was mediated by the pore-forming exotoxin alveolysin, which increased the production of the membrane-anchored protein CD59 and of cilia- and flagella-associated protein 100 (CFAP100) in intestinal epithelial cells. In vitro, CFAP100 interacted with microtubules and promoted microtubule polymerization. CFAP100 overexpression stabilized microtubules in intestinal epithelial cells, leading to disorganization of the microtubule network and perturbation of tight and adherens junctions. The disruption of cell junctions by alveolysin depended on the increase in CFAP100, which in turn depended on CD59 and the activation of PI3K-AKT signaling. These findings demonstrate that, in addition to forming membrane pores, B. cereus alveolysin can permeabilize the intestinal epithelium by disrupting epithelial cell junctions in a manner that is consistent with intestinal symptoms and may allow the bacteria to escape the intestine and cause systemic infections. Our results suggest the potential value of targeting alveolysin or CFAP100 to prevent B. cereus-associated intestinal diseases and systemic infections.

Src inhibition induces mitotic arrest associated with chromosomal passenger complex.

The non-receptor tyrosine kinase Src plays a key role in cell division, migration, adhesion, and survival. Src is overactivated in several cancers, where it transmits signals that promote cell survival, mitosis, and other important cancer hallmarks. Src is therefore a promising target in cancer therapy, but the underlying mechanisms are still uncertain. Here we show that Src is highly conserved across different species. Src expression increases during mitosis and is localized to the chromosomal passenger complex. Knockdown or inhibition of Src induces multipolar spindle formation, resulting in abnormal expression of the Aurora B and INCENP components of the chromosomal passenger complex. Molecular mechanism studies have found that Src interacts with and phosphorylates INCENP. This then leads to incorrect chromosome arrangement and segregation, resulting in cell division failure. Herein, Src and chromosomal passenger complex co-localize and Src inhibition impedes mitotic progression by inducing multipolar spindle formation. These findings provide novel insights into the molecular basis for using Src inhibitors to treat cancer.

RNA sequencing of myeloid sarcoma, shed light on myeloid sarcoma stratification.

BACKGROUND: Myeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic abnormalities in MS. In particular, the broad variety of gene fusions that occur in MS is marginally covered by traditional testing methods due to lack of fresh tumor specimens. METHODS: Here, we analyzed the clinical and genetic features of 61 MS cases. We performed RNA sequencing (RNA-seq) on formalin-fixed paraffin-embedded (FFPE) or fresh samples to analyze fusion genes in 26 cases. In addition, we performed genetic abnormalities-based risk stratification using fusion genes and gene mutations. RESULTS: A total of 305 fusion genes were identified in 22 cases, including the following five recurrent fusion genes: RUNX1-RUNX1T1, CBFß-MYH11, ETV6-MECOM, FUS-ERG, and PICALM-MLLT10. The prognosis in the adverse-risk group was significantly worse than that in the favorable/intermediate-risk group (median survival: 12 months vs. not reached; p = 0.0004). CONCLUSION: These results indicated the efficacy of RNA-seq using FFPE-derived RNA as a clinical routine for detecting fusion genes, which can be used as markers for risk stratification in MS.

Upregulation of ENKD1 disrupts cellular homeostasis to promote lymphoma development.

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive form of B cell lymphoma. Approximately 40% of DLBCL patients are incurable despite modern therapeutic approaches. To explore the molecular mechanisms driving the growth and progression of DLBCL, we analyzed genes with differential expression in DLBCL using the Gene Expression Profiling Interactive Analysis database. Enkurin domain-containing protein 1 (ENKD1), a centrosomal protein-encoding gene, was found to be highly expressed in DLBCL samples compared with normal samples. The phylogenetic analysis revealed that ENKD1 is evolutionarily conserved. Depletion of ENKD1 in cultured DLBCL cells induced apoptosis, suppressed cell proliferation, and blocked cell cycle progression in the G2/M phase. Moreover, ENKD1 expression positively correlates with the expression levels of a number of cellular homeostatic regulators, including Sperm-associated antigen 5, a gene encoding an important mitotic regulator. These findings thus demonstrate a critical function for ENKD1 in regulating the cellular homeostasis and suggest a potential value of targeting ENKD1 for the treatment of DLBCL.

Effects of solvent polarity on the novel excited-state intramolecular thiol proton transfer and photophysical property compared with the oxygen proton transfer.

Recently, the dual-fluorescent phenomena of excited state intramolecular thiol proton transfer (ESIPT) for 3-thiolflavone derivative (3NTF) were reported by Chou and coworkers for the first time [J. Am. Chem. Soc. 143 (2021) 12715-12724], which opened a new chapter in the field of ESIPT. Based on density functional theory (DFT) and time-dependent density functional theory (TDDFT), the proton transfer processes of 3NTF in toluene, dichloromethane and acetonitrile were studied. By optimizing the structure of the ground (S0) state and first excited (S1) state of 3NTF in different solvents, the hydrogen-bond parameters and proton-transfer potential energy curves were calculated. It was shown that although photo-excitation enhanced the intramolecular hydrogen bonding strength and thus promoted the occurrence of ESIPT, the solvent polarities inhibited the enhancement of the hydrogen bond of S1 state, which was not conducive to ESIPT. The electron spectra analyses were consistent with experimental data, which confirmed the rationality of molecular configurations. The time-evolved excited state dynamics simulation was performed based on the optimized structure of 3NTF, indicating that the ESIPT was an ultrafast photochemical reaction less than 180 fs. Moreover, we compared the potential energy surfaces of ESIPT, electronic structures based on natural transition orbitals (NTOs) method and electron-hole isosurfaces for the 3NTF and the traditional flavone molecule (3NHF), concluded that the unusually large Stokes shift fluorescence of 3NTF was mainly caused by the coupling of ESIPT and twisting intramolecular charge transfer (TICT), and the 3NTF isomer had the more nπ* character in the electron transition process. The nπ* ICT significantly increased with the decrease of solvent polarities, affecting the molecular photophysical properties, this made it more widely used in biomedical, photochemical, materials science and other fields.

Peripheral and central control of obesity by primary cilia.

Primary cilia are hair-like structures that protrude from the cell surface. They are capable of sensing external cues and conveying a vast array of signals into cells to regulate a variety of physiological activities. Mutations in cilium-associated genes are linked to a group of diseases with overlapping clinical manifestations, collectively known as ciliopathies. A significant proportion of human ciliopathy cases are accompanied by metabolic disorders such as obesity and type 2 diabetes. Nevertheless, the mechanisms through which dysfunction of primary cilia contributes to obesity are complex. In this review, we present an overview of primary cilia and highlight obesity-related ciliopathies. We also discuss the potential role of primary cilia in peripheral organs, with a focus on adipose tissues. In addition, we emphasize the significance of primary cilia in the central regulation of obesity, especially the involvement of ciliary signaling in the hypothalamic control of feeding behavior. This review therefore proposes a framework of both peripheral and central regulation of obesity by primary cilia, which may benefit further exploration of the ciliary role in metabolic regulation.

Multi-targeted fluorescent probes for detection of Zn(II) and Cu(II) ions based on ESIPT mechanism.

With the rapid development of industry, it is pretty critical to detect the heavy metals. Recently, the 2-(2-hydroxyphenyl) benzothiazole derivatives with different numbers of rotatable phenyl m (m = 1,2,3) fluorescent probes HLm were synthesized. However, the theoretical analysis of the mechanism was still missing. In this work, we have systematically researched the mechanisms of excited state intramolecular proton transfer (ESIPT) and the detection of Cu(II), Zn(II) ions for the hydrogen-bond system HLm though quantum chemistry methods. By bond parameters and the minimum energy pathways analyses, the proton of this system was probed directly transfer without barrier. Bond parameters, real space function at bond critical point, the frontier molecular orbital, electron spectra and orbital interaction diagram were carried to elucidate response to Cu(II), Zn(II) ions. In addition, comparing the Gibbs free energy variation of the complexation reaction between fluorescent probes and ions, it can be proved that the number of rotatable benzene rings affects the response ability of the probe to target ions.

Insights from computational analysis: Excited-state hydrogen-bonding interactions and ESIPT processes in phenothiazine derivatives.

Organic materials with Mechanofluorochromism (MFC) properties have potential application value. Phenothiazine derivatives are a class of substances with MFC properties that have been synthesized and reported in experiments (Dyes and Pigments 172 (2020) 107835). Dual fluorescence of a series of phenothiazine derivatives is observed in the experiment, which proved that the ESIPT process is carried out. In this work, we choose phenothiazine derivatives (C2PAHN, C4PAHN, C8PAHN) as models to theoretically analyze the influence of different alkyl chain lengths on the excited state intramolecular proton transfer (ESIPT). In addition, the shift value of fluorescence spectrum is related to the length of alkyl chain. The fluorescence shift of C2PAHN is the largest (6.31 nm), and that of C8PAHN is the smallest (2.40 nm). The theory of density functional theory (DFT) and time-dependent density functional theory (TD-DFT) are adopted to simulate the molecular dynamics in the ground state and excited state. The analysis of the optimized molecular geometry parameters and infrared vibrational spectroscopy (IR) illustrate the stronger hydrogen bonding of the excited state molecules, which is favorable for the progress of ESIPT. Fluorescence spectroscopy reveals that the appropriate increase or decrease of alkyl chains would change the photophysical properties of the molecules. Frontier molecular orbitals (FMOs) indicate that the rearrangement of electron density from electronic level to is the driving force of the ESIPT process. Reduction density gradient (RDG) surfaces and Natural Population Analysis (NPA) tentatively lead to the conclusion that alkyl chain length is inversely proportional to hydrogen bond strength. Finally, the data are qualitatively analyzed by scanning the potential energy curves, and it is concluded that the longer the alkyl chain, the weaker the hydrogen bonding effect and the more unfavorable the ESIPT process.