Rhodamine Conjugates Research Articles

Covalently grafting multihydroxy hyperbranched polymer on the surface of Ti3C2Tx MXene with remarkably enhanced colloidal stability and functionality for photothermal therapy

While MXenes have garnered acknowledgment for their remarkable photothermal properties, their practical usage has been hindered by their limited stability in aqueous mediums and vulnerability to external environmental factors. To address this issue, herein, we propose a simple and feasible method to enhance Ti3C2Tx MXene by utilizing its Ti-OH groups to directly initiate the ring-opening polymerization of glycidol. This process leads to covalently grafting multihydroxy hyperbranched polyglycerol (HPG) on the surface of MXene. The resulting Ti3C2-HPG nanohybrid demonstrates excellent aqueous dispersibility, favorable colloidal stability, and a customizable surface, thanks to the introduction of HPG. Moreover, it can withstand challenging conditions, such as extreme pH levels, high concentrations of electrolyte and bovine serum protein, and long-time storage. The abundant hydroxyl groups allow for easy modification, as demonstrated by the conjugation of rhodamine B. Preliminary in vitro and in vivo studies have unveiled that Ti3C2-HPG exhibits low cytotoxicity and exceptional photothermal performance for effectively destroying cancer cells, thus establishing it as a highly promising photothermal agent for photothermal therapy. This study thus open a new avenue for improving the stability and surface functionality of MXenes, enabling them to meet the specific requirements of practical applications.

Through bond energy transfer (TBET)-based chemosensor with large Stokes shift for colorimetric and fluorogenic determination of Fe3+ in aqueous system and intracellular imaging application

Chemosensor based on through-bond energy transfer (TBET) mechanism with triazaborolopyridinium (TBP) fluorophore as energy donor and rhodamine fluorophore as energy acceptor was designed, and its Fe3+ ion sensing properties were investigated in aqueous media. Prominent change of solution from yellow to pink and turn-on fluorescence emission was realized by employing Fe3+ selective recognition to form a Fe3+-rhodamine conjugate giving rise to emission at 590 nm with a large Stokes shift (210 nm) under the excitation at 380 nm. This sensor was highly selective and sensitive for distinguishing Fe3+ ions from other common cations. Interestingly, the achieved chemosensor exhibits the detection limits of 32 ppb and 14 ppb for chromogenic and fluorometric analysis, respectively, which are lower than the WHO and U.S. EPA permissible levels in drinking water. The reversible behavior of the Fe3+-sensor complex with the alternate additions of hydrazine and Fe3+ could establish the potential reusability. Moreover, the sensor has also been successfully applied for imaging the presence of Fe3+ ions in living cells.

Developing an Amide-Spacered Triterpenoid Rhodamine Hybrid of Nano-Molar Cytotoxicity Combined with Excellent Tumor Cell/Non-Tumor Cell Selectivity.

Asiatic acid, a pentacyclic triterpene, was converted into a series of piperazinyl, homopiperazinyl, and 1,5-diazocinyl spacered rhodamine conjugates, differing in the type of spacer and the substitution pattern on the rhodamine moiety of the hybrids. The compounds were tested for cytotoxic activity in SRB assays and compound 12, holding an EC50 of 0.8 nM, was the most cytotoxic compound of this series, but compound 18 (containing a ring expanded 1,5-diazocinyl moiety and n-propyl substituents on the rhodamine) was the most selective compound exhibiting a selectivity factor of almost 190 while retaining high cytotoxicity (EC50 = 1.9 nM, for A2780 ovarian carcinoma).

The Finally Rewarding Search for A Cytotoxic Isosteviol Derivative.

Acid hydrolysis of stevioside resulted in a 63% yield of isosteviol (1), which served as a starting material for the preparation of numerous amides. These compounds were tested for cytotoxic activity, employing a panel of human tumor cell lines, and almost all amides were found to be non-cytotoxic. Only the combination of isosteviol, a (homo)-piperazinyl spacer and rhodamine B or rhodamine 101 unit proved to be particularly suitable. These spacered rhodamine conjugates exhibited cytotoxic activity in the sub-micromolar concentration range. In this regard, the homopiperazinyl-spacered derivatives were found to be better than those compounds with piperazinyl spacers, and rhodamine 101 conjugates were more cytotoxic than rhodamine B hybrids.

Design, synthesis and anticancer evaluation of novel oncolytic peptide-chlorambucil conjugates

Nitrogen mustards (NMs) are an important class of chemotherapeutic drugs and have been widely employed for the treatment of various cancers. However, due to the high reactivity of nitrogen mustard, most NMs react with proteins and phospholipids within the cell membrane. Therefore, only a very small fraction of NMs can reach the reach nucleus, alkylating and cross-linking DNA. To efficiently penetrate the cell membrane barrier, the hybridization of NMs with a membranolytic agent may be an effective strategy. Herein, the chlorambucil (CLB, a kind of NM) hybrids were first designed by conjugation with membranolytic peptide LTX-315. However, although LTX-315 could help large amounts of CLB penetrate the cytomembrane and enter the cytoplasm, CLB still did not readily reach the nucleus. Our previous work demonstrated that the hybrid peptide NTP-385 obtained by covalent conjugation of rhodamine B with LTX-315 could accumulate in the nucleus. Hence, the NTP-385-CLB conjugate, named FXY-3, was then designed and systematically evaluated both in vitro and in vivo. FXY-3 displayed prominent localization in the cancer cell nucleus and induced severe DNA double-strand breaks (DSBs) to trigger cell apoptosis. Especially, compared with CLB and LTX-315, FXY-3 exhibited significantly increased in vitro cytotoxicity against a panel of cancer cell lines. Moreover, FXY-3 showed superior in vivo anticancer efficiency in the mouse cancer model. Collectively, this study established an effective strategy to increase the anticancer activity and the nuclear accumulation of NMs, which will provide a valuable reference for future nucleus-targeting modification of nitrogen mustards.

A Study of Small Molecule-Based Rhodamine-Derived Chemosensors and their Implications in Environmental and Biological Systems from 2012 to 2021: Latest Advancement and Future Prospects.

Rhodamine-based chemosensors have sparked considerable interest in recent years due to their remarkable photophysical properties, which include high absorption coefficients, exceptional quantum yields, improved photostability, and significant red shifts. This article presents an overview of the diverse fluorometric, and colorimetric sensors produced from rhodamine, as well as their applications in a wide range of fields. The ability of rhodamine-based chemosensors to detect a wide range of metal ions, including Hg+2, Al3+, Cr3+, Cu2+, Fe3+, Fe2+, Cd2+, Sn4+, Zn2+, and Pb2+, is one of their major advantages. Other applications of these sensors include dual analytes, multianalytes, and relay recognition of dual analytes. Rhodamine-based probes can also detect noble metal ions such as Au3+, Ag+, and Pt2+. They have been used to detect pH, biological species, reactive oxygen and nitrogen species, anions, and nerve agents in addition to metal ions. The probes have been engineered to undergo colorimetric or fluorometric changes upon binding to specific analytes, rendering them highly selective and sensitive by ring-opening via different mechanisms such as Photoinduced Electron Transfer (PET), Chelation Enhanced Fluorescence (CHEF), Intramolecular Charge Transfer (ICT), and Fluorescence Resonance Energy Transfer (FRET). For improved sensing performance, light-harvesting dendritic systems based on rhodamine conjugates has also been explored for enhanced sensing performance. These dendritic arrangements permit the incorporation of numerous rhodamine units, resulting in an improvement in signal amplification and sensitivity. The probes have been utilised extensively for imaging biological samples, including imaging of living cells, and for environmental research. Moreover, they have been combined into logic gates for the construction of molecular computing systems. The usage of rhodamine-based chemosensors has created significant potential in a range of disciplines, including biological and environmental sensing as well as logic gate applications. This study focuses on the work published between 2012 and 2021 and emphasises the enormous research and development potential of these probes.

Porous Silicon Nanocarriers Boost the Immunomodulation of Mitochondria-Targeted Bovine Serum Albumins on Macrophage Polarization.

The development of nanosystems with intrinsic immunomodulatory effects on macrophage polarization is important for the macrophage-targeted immunotherapy. Here, mitochondria-targeted bovine serum albumins (BSAs) via the conjugation of fluorescent, lipophilic, and cationic rhodamine 110 molecules can efficiently enhance the gene expression of the proinflammatory phenotype of macrophages and correspondingly inhibit the gene expression of their anti-inflammatory phenotype. On this basis, porous silicon nanocarriers can further boost the immunomodulation of these mitochondria-targeted BSAs in vitro or in vivo, accompanied by the secretion of proinflammatory mediators including tumor necrosis factor α, nitric oxide, and reactive oxygen species (ROS). Meanwhile, BSA coatings can also improve the biocompatibility of porous silicon nanoparticulate cores on macrophages. Finally, the mechanism investigations demonstrate that porous silicon nanocarriers can efficiently deliver mitochondria-targeted BSA into macrophages to generate mitochondrial ROS via the interference with mitochondrial respiratory chains, which can further trigger the downstream signaling transduction pathways for the proinflammatory transition. Considering the good biosafety and versatile loading capability, this developed porous silicon@BSA nanosystem with a strong proinflmmatory regulatory effect has important potential on the combinatorial chemoimmunotherapy against cancer or viral/bacterial-related infectious diseases.

On the influence of the rhodamine substituents onto the cytotoxicity of mitocanic maslinic acid rhodamine conjugates

Maslinic acid was converted via a di-acetylated piperazinyl amide into rhodamine conjugates differing in their alkyl moieties. These conjugates were submitted to cytotoxicity assays employing a panel of human tumor cell lines. These conjugates held high cytotoxicity but also some selectivity especially for A2780 cells. Thereby, a propyl substituted rhodamine conjugate showed EC50 values as low as EC50 = 0.01 μM and was approx. 15 times more cytotoxic for the cancer cells than for non-malignant fibroblasts (NIH 3 T3). Cytotoxicity obviously parallels the lipophilicity of the residue and suggests - since the compounds act as mitocanes - an interaction of the conjugates with the inner mitochondrial membrane.

A novel highly selective FRET sensor for Fe(III) and DFT mechanistic evaluation

A novel FRET-based sensor has been designed and developed through the conjugation of naphthyl and rhodamine via propylamine spacer, Naph-Rh. The naphthyl moiety serves as a FRET donor due to its emission spectrum overlapping with the rhodamine B absorption band. Naph-Rh exhibited a selectivity for sensing Fe3+ over other metal ions with a visual color change and fluorescent enhancement. The ratio of the Naph-Rh and Fe3+ was determined to be 1:1 based on Job’s plot analysis with a detection limit of 83 nM. The probe exhibited a linear response to Fe3+ in the range of 0–120 μM. Furthermore, the density functional theory (DFT) calculations of Naph-Rh were carried out to rationalize the design and portray the plausible Fe3+ sensing mechanism.

Chiroptical detection of self-aggregating fluorescent rhodamine conjugates: Mistakes and prospects.

Fluorescent conjugation can be considered as the chromophoric derivatization of the target, and as such, it may provide additional structure-related information available by using circular dichroism (CD) spectroscopy. In this essay, peculiar CD spectroscopic data reported earlier for thyroid hormone-rhodamine conjugates have been re-evaluated. Contrary to the original proposal on the intramolecular folding of the labelled hormone, the bisignate motif observed in the CD spectrum is a clear evidence of dye-dye intermolecular chiral exciton coupling, indicating supramolecular self-association of the conjugates. This anomalous solution behaviour undermines the credibility of experimental results reported with such conjugates still being used in the laboratory practice. The extension of routine far-ultraviolet (UV) CD spectroscopic scans of chiral fluorophore conjugates into the near-UV and visible spectral region is strongly recommended.

Fully Automated Screening of a Combinatorial Library to Avoid False Positives: Application to Tetanus Toxoid Ligand Identification.

Peptide ligands are widely used in protein purification by affinity chromatography. Here, we applied a fully automated two-stage library screening method that avoids false positive peptidyl-bead selection and applied it to tetanus toxoid purification. The first library screening was performed using only sulforhodamine (a fluorescent dye), and fluorescent beads were isolated automatically by flow cytometry and discarded. A second screening was then performed with the rest of the library, using the target protein (tetanus toxoid)–rhodamine conjugate. This time, fluorescent beads were isolated, and peptide sequences were identified by matrix-assisted laser desorption/ionization tandem mass spectrometry. Those appearing with greater frequency were synthesized and immobilized on agarose to evaluate a range of chromatographic purification conditions. The affinity matrix PTx1-agarose (Ac-Leu-Arg-Val-Tyr-His-Gly-Gly-Ala-Gly-Lys-agarose) showed the best performance when 20 mM sodium phosphate, 0.05% Tween 20, pH 5.9 as adsorption buffer and 100 mM Tris-HCl, 100 mM NaCl, pH 8.0 as elution buffer were used. A pure tetanus toxoid (Ttx) was loaded on a chromatographic column filled with the PTx1 matrix, and 96% adsorption was achieved, with a Kd of 9.18 ± 0.07 nmol/L and a qm of 1.31 ± 0.029 μmol Ttx/mL matrix. Next, a Clostridium tetani culture supernatant treated with formaldehyde (to obtain the toxoid) was applied as a sample. The sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed a band, identified by electrospray ionization mass spectrometry as the Ttx, that appeared only in the elution fraction, where an S-layer protein was also detected.

A Novel Quinoxaline-Rhodamine Conjugate for a Simple and Efficient Detection of Hydrogen Sulphate Ion

This work presents the development of a quinoxaline and rhodamine conjugate system that acts as a colorimetric chemosensor for hydrogen sulfate (HSO4−) ions in methanol media. This sensor has been characterized both theoretically and experimentally. The detection limits for HSO4− are small as 0.71 µM and 3.8 µM for the absorption and emission experiments, respectively. The effectiveness of the probe in recognizing HSO4− both in gel and solid phase is evaluated as well. Thus, this works presents a simple strategy to detect the environmental HSO4− pollutant event at tiny concentrations.

A novel chemosensor for the distinguishable detections of Cu2+ and Hg2+ by off–on fluorescence and ratiometric UV–visible absorption

A novel dual-functional chemosensor, derived from the conjugation of rhodamine B with a quinoline derivative (RHQ), was firstly synthesized with high efficiency and cost-effectiveness for the distinguishable detections of Cu2+ and Hg2+ via ring-opening and ring-forming mechanism. The chemosensor exhibits highly selective and distinguishable responses for Cu2+ and Hg2+ in CH3CN–H2O (4:1, v/v) with off–on fluorescence and ratiometric ultraviolet–visible (UV–Vis) absorption changes. Additionally, Cu2+ is identified by opening a rhodamine spirocycle with a UV–Vis absorption band, at around 560 nm and fluorescence turn-on. Interestingly, Hg2+ is discerned by opening the rhodamine spirocycle and by generating a new special cycle for the quinoline unit. Resultantly, there were two UV–Vis absorption bands at around 365 nm and 560 nm, which were accompanied by fluorescence turn-on. Moreover, the chemosensor can quantitatively detect Cu2+ and Hg2+ by off–on fluorescence and ratiometric UV–Vis absorption changes, respectively. Furthermore, the chemosensor with low cytotoxicity could be successfully administered to monitor Cu2+ and Hg2+ in living cells. This work may pay the way for the development of dual-functional chemosensor for quantificationally detecting metal ions in environmental and biological systems.

Rhodamine B conjugate for rapid colorimetric and fluorimetric detection of aluminium and tin ions and its application in aqueous media

A new fluorescent chemosensor (MEK) was synthesized from conjugation of rhodamine B hydrazide and methyl ethyl ketone. It exhibited features that would facilitate the ‘naked-eye’ detection, including excellent selectivity and high sensitivity towards Al3+ and Sn2+ ions. Stronger binding strength was recorded in the formation of sensor-Al3+ complex, where the binding constant (Ka) was 3.58 × 1010 M−1. Detection limits of MEK for Sn2+ and Al3+ was 5.10 μM and 8.96 μM respectively. Moreover, a 1:2 and 1:1 binding stoichiometry between this sensor with Al3+ and Sn2+ was verified via Job’s plot and ESI-MS. Reversibility of the sensor as metal ions detector was evaluated with the introduction of the common quencher EDTA and it showed that MEK can be used repeatedly up to 6 times. Differences in the fluorescence profiles of sensor and the sensor-metal complexes (Al3+ and Sn2+) suggested the possible applications of MEK as detection kit for these metal ions. Interestingly, the on-site assay study shown obvious colour changes and fluorescence, thereby reflecting a potentially useful way in differentiating Al3+ and Sn2+. The combination of significant fluorescence response along with tunable selectivity is therefore notably practical for the application of this sensor.

Synthesis and cytotoxic evaluation of hydroxycinnamic acid rhodamine B conjugates

Four different hydroxycinnamic acid rhodamine B conjugates have been prepared and screened for their cytotoxic activity. In the sulforhodamine B (SRB) assay the majority of the conjugates displayed good cytotoxicity in the low μM range for different human tumor cell lines. Low EC50 values were obtained especially for an apoptose-triggering cinnamic acid rhodamine conjugate 3 holding a piperazinyl spacer and a cinnamoyl moiety.

Versatile Synthetic Route for Resveratrol Modification via Amine Functionalization

Resveratrol derivatives containing a primary amine functional group were synthesized by an introduction of N-Boc-bromoethylamine to resveratrol using Williamson ether synthesis and subsequent deprotection of the Boc group with trifluoroacetic acid. After conjugation of fluorescent NBD-F or rhodamine B with isothiocyanate (Rhd B-ITC) using the amine group, resveratrols modified with NBD or Rhd B (Resveratrol-NBD and Resveratrol-Rhd B, respectively) were successfully obtained.

Proximity-Induced Bioorthogonal Chemistry Using Inverse Electron Demand Diels-Alder Reaction.

Bioorthogonal chemistry techniques enable the selective and targeted manipulation of living systems. In order to yield universally applicable techniques, it is of great importance for bioorthogonal reactions to take place rapidly, selectively, and with the formation of onlybenign side products. One of the reactions that match these criteria well is the inverse electron demand Diels-Alder reaction (DAinv) between tetrazines and strained dienophiles. However, even this prime technique comes with the disadvantage of its reactants having limited stability under physiological conditions. In our protocol, an unreactive and therefore stable DAinv diene/dienophile pair reacts rapidly using DNA hybridization as secondary rate-accelerating process. Due to the fluorogenicity of the presented tetrazine rhodamine conjugate, this method enables the selective screening and evaluation of reactant pairs for proximity-mediated bioorthogonal chemistry.

Visualisation of DCP, a nerve agent mimic, in Catfish brain by a simple chemosensor

A chemosensor, 3-aminophenol-based rhodamine conjugate (ARC) has been developed for visualisation of diethylchlorophosphate (DCP), mimic of a chemical warfare agent, in Catfish brain. The simple detection of DCP by “turn-on” fluorescence property of the chemosensor makes it unique for easy and rapid in vivo and in vitro detection of DCP with the detection limit of 5.6 nM.

Highly sensitive and selective detection of Pd2+ ions using a ferrocene-rhodamine conjugate triple channel receptor in aqueous medium and living cells.

Herein, a novel ferrocene-rhodamine receptor conjugated with an allylimine bridge was facilely synthesized. This triple channel receptor can selectively and sensitively monitor Pd2+ ions through chromogenic, fluorogenic and electrochemical assays in aqueous medium with a low detection limit (8.46 × 10-9 M) and a fast response (<8 min). It can be applied as a fluorescent probe for effective survey of Pd2+ ions in living cells. Moreover, a plausible recognition mode was proposed and rationalized by theoretical calculations.

2'-Deoxy-5-(hydroxymethyl)cytidine: estimation in human cancer cells with a simple chemosensor.

A pyrrole-based rhodamine conjugate (CS-1) has been developed and characterized for the selective detection and quantification of 2′-deoxy-5-(hydroxymethyl)cytidine (5hmC) in human cancer cells with a simple chemosensing method.