The intrabulbar or extrabulbar growth pattern and its surgical outcomes of jugular foramen paragangliomas.

OBJECTIVE: This study is to define a subclassification system of jugular foramen paragangliomas (JFPs) and to demonstrate corresponding microsurgical outcomes of JFPs. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: We conducted a retrospective review of the clinical data of 44 patients with JFPs who underwent surgical management. Extrabulbar(Be) tumor and intrabulbar(Bi) tumor are defined based on the growth patterns, receiver operating characteristic (ROC) curves of the imaging profile were generated and was confirmed based on intraoperative findings. Area Under Curve (AUC), accuracy, sensitivity, and specificity for diagnostic imaging were revealed. We also compared the correlation between the two growth patterns with Fisch's classification, blood loss, lower cranial nerves (LCNs) deficit. RESULTS: There are 27 (69%) cases of Bi tumor and 17 (39%) cases of Be tumor. Significant radiomics features between the two growth patterns were demonstrated, ROC curves achieved excellent AUCs for MRI sequences (T1W1 MRI, MR contrast-enhanced sequence, MR complex sequences and MR complex + DSA by 0.833, 0.833, 0.875, 0.944) and had statistically significant in diagnosis of two growth patterns (P<0.05). There was no statistical correlation between growth patterns of JFPs and intra-operative blood loss. Preoperative LCNs deficits and Fisch's classification of tumors were correlated with the growth patterns of JFPs (P < 0.05). CONCLUSION: We proposetd two growth patterns of JFPs in term of the inferior petrous sinus involvement. Identification of Bi or Be growth patterns preoperatively is helpful to design optimal surgical strategies and minimize postoperative complications.

Application Efficacy of Cluster Nursing in Patients Undergoing Gastrointestinal Endoscopy.

Background: Gastrointestinal endoscopy is a clinical examination of gastrointestinal diseases with pain, nausea, and other discomfort of the patient. Therefore, it is of practical significance to give corresponding nursing intervention for patients undergoing painless gastrointestinal endoscopy. Objective: To probe the application efficacy of cluster nursing in patients undergoing gastrointestinal endoscopy. Design: This was a retrospective study. Setting: This study was carried out in the Department of Endoscopy Room, Funan County Hospital of Traditional Chinese Medicine. Participants: From March 2020 to October 2022, 126 patients who underwent painless gastrointestinal endoscopy were chosen and randomly separated into a control group and research group. Interventions: The control group received routine safety nursing management. The research group adopted safety management guided by a cluster nursing strategy. Primary Outcome Measures: (1) the dosage of anesthetic drug use and examination time (2) hemodynamics (3) occurrence of common adverse events (4) score of bowel preparation (5) scores of anxiety and depression (6) comfort degree and (7) nursing satisfaction. Results: Compared to the control group, the dosage of anesthetic drug use and examination time in the research group were lessened (P < .001, 95% CI: -10.06--7.94 and P < .001, 95% CI: -7.10--4.88), the diastolic blood pressure, systolic blood pressure, and heart rate indexes in the research group were reduced (P = .03, 95% CI:-10.07--5.32; P < .001, 95% CI:-13.87--7.91 and P < .001, 95% CI:-12.23--6.27), the occurrence of adverse events during the examination in the research group was reduced (χ2=8.068, P = .005), the score of bowel preparation in the research group was elevated (P < .001, 95% CI: 1.06-1.56), the scores of anxiety as well as depression in the research group were reduced (P < .001, 95% CI: 10.77-13.35 and P < .001, 95% CI: 7.31-9.53), the comfort score of patients in the research group presented higher (P < .001, 95% CI: 17.77-22.91), and the nursing satisfaction in the research group was elevated (χ2=10.31, P = .001). Conclusion: Cluster nursing for patients with painless gastrointestinal endoscopy combined examination has a positive impact on ensuring the successful completion of the examination, effectively controlling the risk of adverse events, and improving patient satisfaction.

miR-130b-3p involved in the pathogenesis of age-related hearing loss via targeting PPARγ and autophagy.

The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H2O2 and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H2O2, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these H2O2-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL.

The application of Global Trigger Tool in monitoring antineoplastic adverse drug events: a retrospective study.

Objective: This study aimed to establish an antineoplastic drugs trigger tool based on Global Trigger Tool (GTT), to examine the performance by detecting adverse drug events (ADEs) in patients with cancer in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of antineoplastic ADEs. Methods: Based on the triggers recommended by the GTT and those used in domestic and foreign studies and taking into account the scope of biochemical indexes in our hospital, some of them were adjusted. A total of 37 triggers were finally developed. Five hundred medical records of oncology patients discharged in our hospital from 1 June 2020 to 31 May 2021 were randomly selected according to the inclusion and exclusion criteria. These records were reviewed retrospectively by antineoplastic drugs trigger tool. The sensitivity and specificity of the triggers were analyzed, as well as the characteristics and risk factors for the occurrence of ADEs. Results: Thirty-three of the 37 triggers had positive trigger, and the sensitivity rate was 91.8% (459/500). For the specificity, the positive predictive value of overall ADEs was 46.0% (715/1556), the detection rate of ADEs was 63.0% (315/500), the rate of ADEs per 100 admissions was 136.0 (95% CI, 124.1-147.9), and the rate of ADEs per 1,000 patient days was 208.33 (95% CI, 201.2-215.5). The top three antineoplastic drugs related to ADEs were antimetabolic drugs (29.1%), plant sources and derivatives (27.1%), and metal platinum drugs (26.3%). The hematologic system was most frequently involved (507 cases, 74.6%), followed by gastrointestinal system (89 cases, 13.1%). Multivariate logistic regression analysis showed that the number of combined drugs (OR = 1.14; 95% CI, 1.07-1.22; P < 0.001) and the previous history of adverse drug reaction (ADR) (OR = 0.38; 95% CI, 0.23-0.60; P < 0.001) were the risk factors for ADEs. The length of hospital stay (OR = 0.40; 95% CI, 0.14-1.12; P < 0.05) and the previous history of ADR (OR = 2.18; 95% CI, 1.07-4.45; P < 0.05) were the risk factors for serious adverse drug events (SAE). Conclusion: The established trigger tool could be used to monitor antineoplastic drugs adverse events in patients with tumor effectively but still needs to be optimized. This study may provide some references for further research in order to improve the rationality and safety of antineoplastic medications.

Thermosensitive hydrogel containing ethosuximide-loaded multivesicular liposomes attenuates age-related hearing loss in C57BL/6J mice.

Ethosuximide is the first drug reported to protect against age-related hearing loss, but its benefits are hampered by the pronounced side effects generated through systemic administration. We prepared a thermosensitive hydrogel containing ethosuximide-encapsulated multivesicular liposomes (ethosuximide-loaded MVLs-Gel) and evaluated its functional and histological effects on age-related hearing loss in C57BL/6J mice. The MVLs-Gel showed slow sustained-release characteristics up to over 120 h. After 8 weeks of treatment, compared to the oral systemic administration of ethosuximide, intratympanic ethosuximide-loaded MVLs-Gel injection dramatically reduced the loss of age-related spiral ganglion neurons in the apical turns of the mice (low-frequency regions, p < 0.05). Correspondingly, compared to the oral systemic administration group, the intratympanic ethosuximide-loaded MVLs-Gel injection group showed significantly lower auditory brainstem response threshold shifts at stimulus frequencies of 4, 8, and 16 kHz (low-and middle-frequency regions, p < 0.05). In conclusion, intratympanic ethosuximide-loaded MVLs-Gel injection can reach the apical turn of the cochlea, which is extremely difficult with oral systemic administration of the drug. The ethosuximide-loaded MVLs-Gel, as a novel intratympanic sustained-release drug delivery system, attenuated age-related hearing loss in C57BL/6J mice.

Combined Machine Learning, Computational, and Experimental Analysis of the Iridium(III) Complexes with Red to Near-Infrared Emission.

Various coordination complexes have been the subject of experimental and theoretical studies in recent decades because of their fascinating photophysical properties. In this work, a combined experimental and computational approach was applied to investigate the optical properties of monocationic Ir(III) complexes. An interpretative machine learning-based quantitative structure-property relationship (ML/QSPR) model was successfully developed that could reliably predict the emission wavelength of the Ir(III) complexes and provide a foundation for the theoretical evaluation of the optical properties of Ir(III) complexes. A hypothesis was proposed to explain the differences in the emission wavelengths between structurally different individual Ir(III) complexes. The efficacy of the developed model was demonstrated by high R2 values of 0.84 and 0.87 for the training and test sets, respectively. It is worth noting that a relationship between the N-N distance in the diimine ligands of the Ir(III) complexes and emission wavelengths is detected. This effect is most probably associated with a degree of distortion in the octahedral geometry of the complexes, resulting in a perturbed ligand field. This combined experimental and computational approach shows great potential for the rational design of new Ir(III) complexes with the desired optical properties. Moreover, the developed methodology could be extended to other transition-metal complexes.

Rapid Separation of Asiatic Acid, Quercetin, and Kaempferol from Traditional Chinese Medicine Centella asiatica (L.) Urban Using HSCCC-Semi-Prep-HPLC and the Assessment of Their Potential as Fatty Acid Synthase Inhibitors.

The main objective of this study was to rapidly separate asiatic acid (AA), quercetin (QCN), and kaempferol (KPL) from Centella asiatica (L.) Urban using high-speed counter-current chromatography (HSCCC) in tandem with the UV detector of semipreparative high-performance liquid chromatography (Semi-Prep-HPLC) and to evaluate their potential as inhibitors of fatty acid synthetase (FAS). To efficiently prepare large amounts of AA, QCN, and KPL from Centella asiatica (L.) Urban, rapid and simple methods by HSCCC were established respectively based on the partition coefficients (K values) of crude samples. The conditions of HSCCC-Semi-Prep-HPLC for the large-scale separation of AA, QCN, and KPL from Centella asiatica (L.) Urban were established and optimized. This included selecting the solvent system, flow rate, rotation speed, and so on. HSCCC-Semi-Prep-HPLC was successfully applied to separate and purify AA, QCN, and KPL, with n-hexane-n-butanol-methanol-water (3 : 1 : 3 : 3, V : V : V : V) as the solvent system for AA, which was detected at a wavelength of 210 nm with the stationary phase retention of 70%, and with n-hexane-ethyl acetate-methanol-water (0.8 : 0.9 : 1.2 : 1, V : V : V : V) as the solvent system for the co-separation of QCN and KPL, which was detected at a wavelength of 254 nm with the stationary phase retention of 65%. AA could be isolated at a large scale with high purity (>91.0%) in only one-step HSCCC-Semi-Prep-HPLC separation (within 150 min) under the optimized conditions. Meanwhile, QCN and KPL could be simultaneously isolated at a large scale with high purity (>99.1%) by another one-step HSCCC-Semi-Prep-HPLC separation (within 240 min) under the optimized conditions. The assessment of inhibition potential revealed that AA exhibited the strongest inhibitory effect on FAS, with an IC50 of 9.52 ± 0.76 µg/mL. Madecassic acid (MA) followed closely with IC50 values of 10.84 ± 0.92 µg/mL. QCN and KPL showed similar and relatively weaker inhibitory effects on FAS, with IC50 values of 43.09 ± 2.98 µg/mL and 36.90 ± 1.83 µg/mL, respectively. Overall, the HSCCC-Semi-Prep-HPLC method proved to be a highly efficient and reliable technique for separating AA, QCN, and KPL from Centella asiatica (L.) Urban, and the isolated compounds showed potential as FAS inhibitors.

The brief overview, antivirus and anti-SARS-CoV-2 activity, quantitative methods, and pharmacokinetics of cepharanthine: a potential small-molecule drug against COVID-19.

To effectively respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an increasing number of researchers are focusing on the antiviral activity of cepharanthine (CEP), which is a clinically approved drug being used for over 70 years. This review aims to provide a brief overview of CEP and summarize its recent findings in quantitative analysis, pharmacokinetics, therapeutic potential, and mechanism in antiviral and anti-SARS-CoV-2 activity. Given its remarkable capacity against SARS-CoV-2 infection in vitro and in vivo, with its primary target organ being the lungs, and its good pharmacokinetic profile; mature and stable manufacturing technique; and its advantages of safety, effectiveness, and accessibility, CEP has become a promising drug candidate for treating COVID-19 despite being an old drug.

Differentially expressed miRNA profiles of serum-derived exosomes in patients with sudden sensorineural hearing loss.

Objectives: This study aimed to compare the expressed microRNA (miRNA) profiles of serum-derived exosomes of patients with sudden sensorineural hearing loss (SSNHL) and normal hearing controls to identify exosomal miRNAs that may be associated with SSNHL or serve as biomarkers for SSNHL. Methods: Peripheral venous blood of patients with SSNHL and healthy controls was collected to isolate exosomes. Nanoparticle tracking analysis, transmission electron microscopy, and Western blotting were used to identify the isolated exosomes, after which total RNA was extracted and used for miRNA transcriptome sequencing. Differentially expressed miRNAs (DE-miRNAs) were identified based on the thresholds of P < 0.05 and |log2fold change| > 1 and subjected to functional analyses. Finally, four exosomal DE-miRNAs, including PC-5p-38556_39, PC-5p-29163_54, PC-5p-31742_49, and hsa-miR-93-3p_R+1, were chosen for validation using quantitative real-time polymerase chain reaction (RT-qPCR). Results: Exosomes were isolated from serum and identified based on particle size, morphological examination, and expression of exosome-marker proteins. A total of 18 exosomal DE-miRNAs, including three upregulated and 15 downregulated miRNAs, were found in SSNHL cases. Gene ontology (GO) functional annotation analysis revealed that target genes in the top 20 terms were mainly related to "protein binding," "metal ion binding," "ATP binding," and "intracellular signal transduction." Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these target genes were functionally enriched in the "Ras," "Hippo," "cGMP-PKG," and "AMPK signaling pathways." The expression levels of PC-5p-38556_39 and PC-5p-29163_54 were significantly downregulated and that of miR-93-3p_R+1 was highly upregulated in SSNHL. Consequently, the consistency rate between sequencing and RT-qPCR was 75% and sequencing results were highly reliable. Conclusion: This study identified 18 exosomal DE-miRNAs, including PC-5p-38556_39, PC-5p-29163_54, and miR-93-3p, which may be closely related to SSNHL pathogenesis or serve as biomarkers for SSNHL.

Comparative Efficacy and Safety of Five Anti-calcitonin Gene-related Peptide Agents for Migraine Prevention: A Network Meta-analysis.

OBJECTIVES: Anti-calcitonin gene-related peptide (CGRP) agents are some of the newest preventive medications for migraine. There is limited literature comparing the efficacy of the most recent CGRP antagonist, atogepant, to CGRP monoclonal antibodies for migraine prevention. In this network meta-analysis, the efficacy and safety of migraine treatments including different doses of atogepant and CGRP monoclonal antibodies were evaluated to provide a reference for future clinical trials. MATERIALS AND METHODS: A search using PubMed, Embase, and Cochrane Library identified all randomized controlled trials published through May 2022 and including patients diagnosed with episodic or chronic migraine and treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. The primary outcomes were the reduction of monthly migraine days, 50% response rate, and the number of adverse events (AEs). The Cochrane Collaboration tool was used to assess the risk of bias. RESULTS: In this study, 24 articles were considered for analysis. Regarding efficacy, all interventions were superior to placebo with a statistically significant difference. The most effective intervention was monthly fremanezumab 225 mg in change from baseline of migraine days (standard mean difference = -0.49, 95% CI: -0.62, -0.37) and 50% response rate (risk ratio = 2.98, 95% CI: 2.16,4.10), while the optimal choice for reducing acute medication days was monthly erenumab 140 mg (standard mean difference = -0.68, 95% CI: -0.79, -0.58). In terms of AEs, all therapies and placebo did not achieve statistical significance except for monthly galcanezumab 240 mg and quarterly fremanezumab 675 mg. There was no significant difference in discontinuation due to AEs between interventions and placebo. DISCUSSION: All anti-CGRP agents were more effective than placebo in migraine prevention. Overall, monthly fremanezumab 225 mg, monthly erenumab 140 mg, and daily atogepant 60 mg were effective interventions with fewer side effects.

MG-Net: Multi-level global-aware network for thymoma segmentation.

BACKGROUND AND OBJECTIVE: Automatic thymoma segmentation in preoperative contrast-enhanced computed tomography (CECT) images makes great sense for diagnosis. Although convolutional neural networks (CNNs) are distinguished in medical image segmentation, they are challenged by thymomas with various shapes, scales and textures, owing to the intrinsic locality of convolution operations. In order to overcome this deficit, we built a deep learning network with enhanced global-awareness for thymoma segmentation. METHODS: We propose a multi-level global-aware network (MG-Net) for thymoma segmentation, in which the multi-level feature interaction and integration are jointly designed to enhance the global-awareness of CNNs. Particularly, we design the cross-attention block (CAB) to calculate pixel-wise interactions of multi-level features, resulting in the Global Enhanced Convolution Block, which can enable the network to handle various thymomas by strengthening the global-awareness of the encoder. We further devise the Global Spatial Attention Module to integrate coarse- and fine-grain information for enhancing the semantic consistency between the encoder and decoder with CABs. We also develop an Adaptive Attention Fusion Module to adaptively aggregate different semantic-scale features in the decoder to preserve comprehensive details. RESULTS: The MG-Net has been evaluated against several state-of-the-art models on the self-collected CECT dataset and NIH Pancreas-CT dataset. Results suggest that all designed components are effective, and MG-Net has superior segmentation performance and generalization ability over existing models. CONCLUSION: Both the qualitative and quantitative experimental results indicate that our MG-Net with global-aware ability can achieve accurate thymoma segmentation and has generalization ability in different tasks. The code is available at: https://github.com/Leejyuan/MGNet.

Adverse event reporting of four anti-Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: a real-world study based on the FDA adverse event reporting system.

Background: Anti-Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have shown significant efficacy in preventing migraine. However, there have been limited reports of adverse events (AEs) after marketing, particularly for eptinezumab launched in 2020. The study aimed to mine and analyze the AE signals with four anti-CGRP mAbs from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insights into the safety profile of these medications post-marketing. Methods: All AE reports on the four anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) were retrieved from the FAERS database from the first quarter (Q1) of 2018 to Q1 of 2023. Disproportionality analysis was measured by reporting odd ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) to identify potential AE signals. Comparisons were made between the four drugs in terms of AEs. Results: A total of 38,515 reports of erenumab, 19,485 reports of galcanezumab, 5,332 reports of fremanezumab, and 2,460 reports of eptinezumab were obtained, mostly reported in the second to third year after launch in the market. The common AEs to erenumab included constipation (17.93%), injection site pain (14.08%), and alopecia (7.23%). The AEs that occurred more frequently with galcanezumab included injection site pain (24.37%), injection site erythema (5.35%), and injection site haemorrhage (4.97%). Common AEs related to fremanezumab were injection site pain (13.10%), injection site erythema (7.02%), and injection site pruritus (5.47%). Fatigue (13.54%), throat irritation (9.02%), and pruritus (8.20%) were the most common AEs with eptinezumab. In addition, there are new AEs that were not listed in the drug instructions but occurred concurrently with multiple drugs, such as Raynaud's phenomenon, weight increase, menstrual disorders, throat tightness, and paraesthesia oral. Conclusion: Common AE signals of the four anti-CGRP mAbs and new AE signals were found to provide a reference for clinical drug selection in clinical practice.

Improving Near-Infrared Emission of meso-Aryldipyrrin Indium(III) Complexes via Annulation Bridging: Excited-State Dynamics.

Using non-adiabatic dynamics and Redfield theory, we predicted the optical spectra, radiative and nonradiative decay rates, and photoluminescence quantum yields (PLQYs) for In(III) dipyrrin-based complexes (i) with electron-withdrawing (EW) or electron-donating (ED) substituents on the meso-phenyl group and (ii) upon fusing the pyrrin and phenyl rings via saturated or unsaturated bridging to increase structural rigidity. The ED groups lead to a primary π,π* character with a minor intraligand charge transfer (ILCT) contribution to the emissive state, while EW groups increase the ILCT contribution and red-shift the luminescence to ∼1.5 eV. Saturated annulation enhances the PLQYs for complexes with primary π,π* character compared to those of the non-annulated and unsaturated-annulated complexes, while both unsaturated and saturated annulation decrease the PLQYs for complexes with primary ILCT character. We found that PLQY improvement goes beyond a simple concept of structural rigidity. In contrast, the charge transfer character of excitonic states is a key parameter for engineering the NIR emission of In(III) dipyrrin complexes.

Water-soluble dinuclear iridium(III) and ruthenium(II) bis-terdentate complexes: photophysics and electrochemiluminescence.

The synthesis, photophysics, and electrochemiluminescence (ECL) of four water-soluble dinuclear Ir(III) and Ru(II) complexes (1-4) terminally-capped by 4'-phenyl-2,2':6',2''-terpyridine (tpy) or 1,3-di(pyrid-2-yl)-4,6-dimethylbenzene (N^C^N) ligands and linked by a 2,7-bis(2,2':6',2''-terpyridyl)fluorene with oligoether chains on C9 are reported. The impact of the tpy or N^C^N ligands and metal centers on the photophysical properties of 1-4 was assessed by spectroscopic methods including UV-vis absorption, emission, and transient absorption, and by time-dependent density functional theory (TDDFT) calculations. These complexes exhibited distinct singlet and triplet excited-state properties upon variation of the terminal-capping terdentate ligands and the metal centers. The ECL properties of complexes 1-3 with better water solubility were investigated in neutral phosphate buffer solutions (PBS) by adding tripropylamine (TPA) as a co-reactant, and the observed ECL intensity followed the descending order of 3 > 1 > 2. Complex 3 bearing the [Ru(tpy)2]2+ units displayed more pronounced ECL signals, giving its analogues great potential for further ECL study.

Photophysics and reverse saturable absorption of cationic dinuclear iridium(III) complexes bearing fluorenyl-tethered 2-(quinolin-2-yl)quinoxaline ligands.

The synthesis, photophysics and reverse saturable absorption of two cationic dinuclear Ir(III) complexes bearing fluorenyl-tethered 2-(quinolin-2-yl)quinoxaline (quqo) ligands are reported in this paper. The two complexes possess intense and featureless diimine ligand localized 1ILCT (intraligand charge transfer)/1π,π* absorption bands at ca. 330 and 430 nm, and a weak 1,3MLCT (metal-to-ligand charge transfer)/1,3LLCT (ligand-to-ligand charge transfer) absorption band at >500 nm. Both complexes exhibit weak dual phosphorescence at ca. 590 nm and 710 nm, which are attributed to the 3ILCT/3π,π* and 3MLCT/3LLCT states, respectively. The low-energy 3MLCT/3LLCT state also gives rise to a moderately strong triplet excited-state absorption at 490-800 nm. Because of the stronger triplet excited-state absorption than the ground-state absorption of these complexes at 532 nm, both complexes manifest a moderate reverse saturable absorption (RSA) at 532 nm for ns laser pulses. Expansion of the π-conjugation of the fluorenyl-tethered diimine ligand in Ir-1 causes a slight red-shift of the 1ILCT/1π,π* absorption bands in its UV-vis absorption spectrum and the 3MLCT/3LLCT absorption band in the transient absorption spectrum and slightly enhances the RSA at 532 nm compared to that in Ir-2. This work represents the first report on dinuclear Ir(III) complexes that exhibit RSA at 532 nm.

Mono-/Bimetallic Neutral Iridium(III) Complexes Bearing Diketopyrrolopyrrole-Substituted N-Heterocyclic Carbene Ligands: Synthesis and Photophysics.

The synthesis and photophysics (UV-vis absorption, emission, and transient absorption) of four neutral heteroleptic cyclometalated iridium(III) complexes (Ir-1-Ir-4) incorporating thiophene/selenophene-diketopyrrolopyrrole (DPP)-substituted N-heterocyclic carbene (NHC) ancillary ligands are reported. The effects of thiophene versus selenophene substitution on DPP and bis- versus monoiridium(III) complexation on the photophysics of these complexes were systematically investigated via spectroscopic techniques and density functional theory calculations. All complexes exhibited strong vibronically resolved absorption in the regions of 500-700 nm and fluorescence at 600-770 nm, and both are predominantly originated from the DPP-NHC ligand. Complexation induced a pronounced red shift of this low-energy absorption band and the fluorescence band with respect to their corresponding ligands due to the improved planarity and extended π-conjugation in the DPP-NHC ligand. Replacing the thiophene units by selenophenes and/or biscomplexation led to the red-shifted absorption and fluorescence spectra, accompanied by the reduced fluorescence lifetime and quantum yield and enhanced population of the triplet excited states, as reflected by the stronger triplet excited-state absorption and singlet oxygen generation.

Extending Fluorescence of meso-Aryldipyrrin Indium(III) Complexes to Near-Infrared Regions via Electron Withdrawing or π-Expansive Aryl Substituents.

The absorption and fluorescence spectra of 14 In(III) dipyrrin-based complexes are studied using time-dependent density functional theory (TDDFT). Calculations confirm that both heteroatom substitution of oxygen (N2O2-type) by nitrogen (N4-type) in dipyrrin ligand and functionalization at the meso-position by aromatic rings with strong electron-withdrawing (EW) substituents or extended π-conjugation are efficient tools in extending the fluorescence spectra of In(III) complexes to the near-infrared (NIR) region of 750-960 nm and in red-shifting the lowest absorption band to 560-630 nm. For all complexes, the emissive singlet state has π-π* character with a small addition of intraligand charge transfer (ILCT) contributing from the meso-aryl substituents to the dipyrrin ligand. Stronger EW nitro group on the meso-phenyl or meso-aryl group with extended π-conjugation induces red-shifted electronic absorption and fluorescence. More tetrahedral geometry of the complexes with N4-type ligands leads to less intensive but more red-shifted fluorescence to NIR, compared to the corresponding complexes with N2O2-type ligands that have a more planar geometry.

Highly Efficient Far-Red/NIR-Absorbing Neutral Ir(III) Complex Micelles for Potent Photodynamic/Photothermal Therapy.

A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light-to-ROS conversion efficiency with far-red/near-infrared (NIR) light excitation due to low-lying excited states that lead to rapid non-radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY-Ir) is reported to efficiently produce both ROS and hyperthermia upon far-red light activation for potentiating in vivo tumor suppression through micellization of BODIPY-Ir to form "Micelle-Ir". BODIPY-Ir absorbs strongly at 550-750 nm with a band maximum at 685 nm, and possesses a long-lived triplet excited state with sufficient non-radiative decays. Upon micellization, BODIPY-Ir forms J-type aggregates within Micelle-Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light-to-ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle-Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far-red/NIR photosensitizers toward potent cancer therapy.

Multinuclear 2-(Quinolin-2-yl)quinoxaline-Coordinated Iridium(III) Complexes Tethered by Carbazole Derivatives: Synthesis and Photophysics.

Five mono/di/trinuclear iridium(III) complexes (1-5) bearing the carbazole-derivative-tethered 2-(quinolin-2-yl)quinoxaline (quqo) diimine (N^N) ligand were synthesized and characterized. The photophysical properties of these complexes and their corresponding diimine ligands were systematically studied via UV-vis absorption, emission, and transient absorption (TA) spectroscopy and simulated by time-dependent density functional theory. All complexes possessed strong well-resolved absorption bands at <400 nm that have predominant ligand-based 1π,π* transitions and broad structureless charge-transfer (1CT) absorption bands at 400-700 nm. The energies or intensities of these 1CT bands varied pronouncedly when the number of tethered Ir(quqo)(piq)2+ (piq refers to 1-phenylisoquinoline) units, π conjugation of the carbazole derivative linker, or attachment positions on the carbazole linker were altered. All complexes were emissive at room temperature, with 1-3 showing near-IR (NIR) 3MLCT (metal-to-ligand charge-transfer)/3LLCT (ligand-to-ligand charge-transfer) emission at ∼710 nm and 4 and 5 exhibiting red or NIR 3ILCT (intraligand charge-transfer)/3LMCT (ligand-to-metal charge-transfer) emission in CH2Cl2. In CH3CN, 1-3 displayed an additional emission band at ca. 590 nm (3ILCT/3LMCT/3MLCT/3π,π* in nature) in addition to the 710 nm band. The different natures of the emitting states of 1-3 versus those of 4 and 5 also gave rise to different spectral features in their triplet TA spectra. It appears that the parentage and characteristics of the lowest triplet excited states in these complexes are mainly impacted by the π systems of the bridging carbazole derivatives and essentially no interactions among the Ir(quqo)(piq)2+ units. In addition, all of the diimine ligands tethered by the carbazole derivatives displayed a dramatic solvatochromic effect in their emission due to the predominant intramolecular charge-transfer nature of their emitting states. Aggregation-enhanced emission was also observed from the mixed CH2Cl2/ethyl acetate or CH2Cl2/hexane solutions of these ligands.

DNA-Targeting RuII -Polypyridyl Complex with a Long-Lived Intraligand Excited State as a Potential Photodynamic Therapy Agent.

Subtle ligand modifications on RuII -polypyridyl complexes may result in different excited-state characteristics, which provides the opportunity to tune their photo-physicochemical properties and subsequently change their biological functions. Here, a DNA-targeting RuII -polypyridyl complex (named Ru1) with highly photosensitizing 3 IL (intraligand) excited state was designed based on a classical DNA-intercalator [Ru(bpy)2 (dppz)]⋅2 PF6 by incorporation of the dppz (dipyrido[3,2-a:2',3'-c]phenazine) ligand tethered with a pyrenyl group, which has four orders of magnitude higher potency than the model complex [Ru(bpy)2 (dppz)]⋅2 PF6 upon light irradiation. This study provides a facile strategy for the design of organelle-targeting RuII -polypyridyl complexes with dramatically improved photobiological activity.