Unique Reaction-Based Polynorbornene Sensing Probes for Ultrasensitive Detection of Hydrazine in Both Environmental and Biological Systems.

Hydrazine-mediated formation of 1,4-phthalazinedione analogues from phthalimide-like components has been utilized to formulate fluorescent probe NorTh. A turn-on fluorescent process has been evaluated to detect hydrazine in a highly selective manner by a small molecular probe NorTh and its homopolymer Poly-NorTh. Both these probes have been evaluated as excellent candidates for nanomolar level detection of hydrazine with a time frame of <15 min, which is rapid in terms of real application. Due to the reaction-based detection process, we have achieved high selectivity for our probes toward the identification of hydrazine in the presence of metal ions, anions, amino acids, and various amines. Limit of detection values are 16 and 35 nM for NorTh and Poly-NorTh, respectively, which are well below the permissible limit given by WHO and EPA. Poly-NorTh has been utilized to detect hydrazine in environmental water samples, soil samples, and biological samples to establish the applicability of our probes in real-field scenarios. We introduce an easy-to-synthesize, cheap, and small molecular probe and its polymer for ultrafast, highly selective, and sensitive detection of hydrazine in all possible mediums to counter the hydrazine toxicity through fluorescence turn-on signal output.

Iron(III) Coordinated Theranostic Polyprodrug with Sequential Receptor-Mitochondria Dual Targeting and T1-Weighted Magnetic Resonance Imaging Potency for Effective and Precise Chemotherapy.

The sequential cancer cell receptor and mitochondria dual-targeting single delivery agent deliver chemotherapeutic drug effectively and precisely at the targeted site has become a promising strategy to enhance the drug efficacy and suppressions of cancer cell drug resistance prominence. Herein, required specialty molecules like a chemotherapeutic drug [camptothecin (CPT)], mitochondriotropic segment (triphenyl phosphonium cation) receptor targeting ligand (biotin), and magnetic resonance imaging (MRI)-contrast agent (iron-complex) were tethered to the polyprodrug, CP TP PG BN Fe, using the ring-opening metathesis polymerization technique for potential chemotherapy and simultaneous MRI-based diagnosis. This amphiphilic polyprodrug spontaneously aggregated into nanospheres and exhibited remarkable T1-weighted MRI proficiency. Detail in vitro cellular studies revealed unambiguous mitochondrial delivery of CPT, which eventually enhanced the chemotherapeutic efficacy of CP TP PG BN Fe. Therefore, MRI-tracking, receptor-mitochondria dual targeting, theranostic polyprodrug, and CP TP PG BN Fe opened the way for effective and precise chemotherapy, which would have the attractive potential for diagnosis and decisive dose determination in clinical implications.

Unique Random-Block Polymer Architecture for Site-Specific Mitochondrial Sequestration-Aided Effective Chemotherapeutic Delivery and Enhanced Fluorocarbon Segmental Mobility-Facilitated 19F Magnetic Resonance Imaging.

The elevation of the chemotherapeutic efficacy and attenuation of its side effects on healthy cells and tissues become one of the prime targets for the treatment of cancer. Toward this direction, a sequential receptor and mitochondria dual-targeting strategy was implemented in the DX TP PG BN 19F theranostic polymer that was anchored with the chemotherapeutic agent doxorubicin, receptor-targeting biotin, and mitochondria-targeting triphenylphosphonium cations. The polymer was flourished with a unique 19F magnetic resonance imaging (MRI) tracer that exhibited high segmental mobility and eventually led to prolonged T2 relaxation time. Furthermore, for the sake of amphiphilicity, the DX TP PG BN 19F polymer spontaneously aggregated into nano-sphere with positive zeta potential, where the MRI tracer and biotin embedded at the exterior and displayed site-specific targeting and remarkable 19F MRI capability simultaneously. The mitochondria-targeting competency of the DX TP PG BN 19F theranostic polymer was investigated by comparing the non-mitochondrial-targeting DX PG BN 19F polymer using fluorescence microscopic cell imaging in human cervical, HeLa, and breast MCF-7 carcinoma cell lines. Moreover, cytotoxicity experiments of the aforementioned theranostic polymers clarified the enhancement of the chemotherapeutic efficacy of DX TP PG BN 19F theranostic polymers through effective and precise mitochondrial doxorubicin delivery that forced to follow the apoptotic path.

Coordinately Tethered Iron(III) Fluorescent Nanotheranostic Polymer Ascertaining Cancer Cell Mitochondria Destined Potential Chemotherapy and T1-Weighted MRI Competency.

Magnetic resonance imaging-aided real-time diagnosis along with enhanced chemotherapeutic efficacy using a sequential receptor and mitochondria dual-targeting polymer theranostic has become a promising strategy for the effective and precise treatment of cancer. Toward the accomplishment of this goal, chlorambucil (chemotherapeutic agent), biotin (receptor targeting agent), a triphenylphosphonium segment (mitochondriotropic agent), and an iron rhodamine complex (integrated fluorescence-MR imaging agent) were tethered under a single polymer. Owing to the polymer's (RD CH PG BN TP Fe) amphiphilic character, it spontaneously self-assembled into nanospheres, which exhibited a remarkable effect on the relaxation of the water proton. Further, the qualitative estimation of the change in intensity for the water-proton signal reflected its potential as a T1 contrast theranostic polymer. The mitochondria targeting competency of positively charged nanospheres was displayed using fluorescence microscopy in human cervical, HeLa, and breast, MCF-7, carcinoma cell lines. Furthermore, cytotoxicity experiments demonstrated the enhanced anticancer efficacy in both cancer cell lines. Therefore, effective and precise chemotherapy through sequential receptor-mitochondria targeting and integrated fluorescence-MR imaging would have attractive potential for decisive dose-determination by constantly monitoring the subject area of interest.

Engineering Spherically Super-Structured Polyamides for the Sustainable Water Remediation.

Unlike metal-ornamented hybrid material and linear polymers, we invoked the growth of a biodegradable superstructured cross-linked polyamide-ester material. The material is thermally stable. The thiol-alkene photoclicked material acted as an efficient water remediator. The material efficiently monitored amphiphilic dyes like rhodamine B (RHB), methylene blue (MB), and chronic mercuric ions in water. The adsorption kinetics revealed the material could adsorb >95% dyes within 24 h. The RHB-functionalized polymer could sense mercuric ions too. The Density functional theory (DFT) calculation shows a chelated mercury complex with thioether in the polymer, Poly-Am-RhAll, to form a comparatively more stable complex.

1,6-heptadiynes based cyclopolymerization functionalized with mannose by post polymer modification for protein interaction.

Carbohydrate functionalized polymers or Glycopolymers have earned a great deal of interest in recent times for their potential biomedical applications. In the present study, a mannose containing glycopolymer was synthesized by cyclopolymerization of malonic acid derivative using second generation Hoveyda Grubbs' catalyst. Post-polymerization modification was done to install a propargyl moiety. Finally, functionalization of the propargylated polymer with 2-azidoethyl mannoside using azide-alkyne "click chemistry" furnished the target glycopolymer which was successfully characterized using NMR, FT-IR, mass spectroscopy and advanced polymer chromatography. The glycopolymer was found to self-assemble into capsule and spherical shape in water and DMSO respectively and these morphologies were observed through SEM and TEM. Upon interaction with Con A, the mannose containing glycopolymer showed an increment in aggregation induced fluorescence with increasing concentration of the lectin. In vitro cytotoxicity studies on MCF 7 cell line showed 90% cell viability up to glycopolymer concentration of 500 µg/mL.

Efficient Design to Monitor the Site-specific Sustained Release of a Non-Emissive Anticancer Drug.

A pH-responsive smart nanocarrier with significant components was synthesized by conjugating the non-emissive anticancer drug methyl orange and polyethylene glycol derived folate moiety to the backbone of polynorbornene. Complete synthesis procedure and characterization methods of three monomers included in the work: norbornene-derived Chlorambucil (Monomer 1), norbornene grafted with polyethylene glycol, and folic acid (Monomer 2) and norbornene attached methyl orange (Monomer 3) connected to the norbornene backbone through ester linkage were clearly discussed. Finally, the random copolymer CHO PEG FOL METH was synthesized by ring-opening metathesis polymerization (ROMP) using Grubbs' second-generation catalyst. Advanced polymer chromatography (APC) was used to find the final polymer's molecular weight and polydispersity index (PDI). Dynamic light scattering, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were utilized to explore the prodrug's size and morphology. Release experiments of the anticancer drug, Chlorambucil and the coloring agent, methyl orange, were performed at different pH and time. Cell viability assay was carried out for determining the rate of survived cells, followed by the treatment of our final polymer named CHO PEG FOL METH.

Hetero-Trifunctional Malonate-Based Nanotheranostic System for Targeted Breast Cancer Therapy.

Designing multifunctional linkers is crucial for tricomponent theranostic targeted nanomedicine development as they are essential to enrich polymeric systems with different functional moieties. Herein, we have obtained a hetero-trifunctional linker from malonic acid and demonstrated its implication as an amphiphilic targeted nanotheranostic system (CB DX UN PG FL). We synthesized it with varying hydrophilic segment to fine-tune the hydrophobic/hydrophilic ratio to optimize its self-assembly. pH-responsive hydrazone-linked doxorubicin was conjugated to the backbone (UN PG FL) containing folate as a targeting ligand. Cobalt carbonyl complex was used for T2-weighted magnetic resonance imaging (MRI). Electron micrographs of optimized molecule CB DX UN PG(4 kDa)FL in an aqueous system have demonstrated about 50-60 nm-sized uniform micelles. The relaxivity study and the one-dimensional (1D) imaging experiments clearly revealed the effect of the nanotheranostics system on transverse relaxation (T2) of water molecules, which validated the system as a T2-weighted MRI contrast agent. The detailed in vitro biological studies validated the targeted delivery and anticancer potential of CB DX UN PG(4 kDa)FL. Combining the data on transverse relaxation, folate mediated uptake, and anticancer activity, the designed molecule will have a significant impact on the development of targeted theranostic.

Unusual red-orange emission from rhodamine-derived polynorbornene for selective binding to Fe3+ ions in an aqueous environment.

Norbornene-based rhodamine derivative (NR) was observed as an "off-on" probe for Fe3+ ions both colorimetrically and fluorimetrically in an aqueous environment. NR and its homopolymer (PNR) were capable of detecting Fe3+ ions with high selectivity and sensitivity in an aqueous environment. For NR and PNR the limit of detection (LOD) towards Fe3+ ions was found to be 49 nM and 19 nM, respectively, making these materials highly efficient. Most interestingly, PNR has more efficacy towards the detection of Fe3+ ions than NR, which is expected due to the favorable side-chain interaction in the presence of multiple sensing motifs between the polymer chains. The sensing behavior was thoroughly studied via spectroscopic techniques. We hypothesized that the Fe3+ ion was expected to induce the spirolactam ring-opening of the rhodamine unit due to its Lewis acid nature and preferable interactions with the N and O atoms present in NR as well as PNR.

Unraveling the Effect of PEG Chain Length on the Physical Properties and Toxicant Removal Capacities of Cross-Linked Network Synthesized by Thiol-Norbornene Photoclick Chemistry.

With the aim to develop chemical adsorbents that are inherently nontoxic to living beings and the environment, a gel system based on thiol-norbornene photoclick chemistry was developed. Norbornene was strategically functionalized with different poly(ethylene glycol) (PEG) chains to produce PEG-functionalized macromonomers. The influence of incorporating PEG in the cross-linked network was evaluated on the basis of its physical properties and dye-removing efficiency from aqueous solutions. The excellent swelling ability of the gels in organic solvents was found to improve with the PEG chain length. The rheological measurements of the as-synthesized materials also exhibited the presence of elasticity in the network, and a decrease in storage and loss moduli was observed with an increase in PEG molecular weight. The materials possess excellent thermal stability, which enhanced with an increase in PEG chain length, as revealed from thermogravimetric analysis (TGA). Differential scanning calorimetry (DSC) studies revealed the tendency of higher-molecular-weight PEG to form a crystalline phase in the network. Kinetic studies of dye removal from aqueous solutions by the as-prepared cross-linked networks indicate that the dye removal proceeds via pseudo-second-order kinetics. The study of adsorption isotherm of the removal process indicates that the adsorption follows the Langmuir isotherm model. In this present work, we have thoroughly evaluated the influence of PEG chain length on several physical properties and toxic cationic dye removal efficiencies of thiol-norbornene photo-cross-linked networks.

"Dial-In" Emission from a Unique Flexible Material with Polarization Tuneable Spectral Intensity.

The development of organic photoluminescent materials, which show promising roles as catalysts, sensors, organic light-emitting diodes, logic gates, etc., is a major demand and challenge for the global scientific community. In this context, a photoclick polymerization method is adopted for the growth of a unique photoluminescent three-dimensional (3D) polymer film, E, as a model system that shows emission tunability over the range 350-650 nm against the excitation range 295-425 nm. The DFT analysis of energy calculations and π-stacking supports the spectroscopic observations for the material exhibiting a broad range of emission owing to newly formed chromophoric units within the film. Full polarization spectroscopic Mueller matrix studies were employed to extract and quantify the molecular orientational order of both the ground (excitation) and excited (emission) state anisotropies through a set of newly defined parameters, namely the fluorescence diattenuation and fluorescence polarizance. The information contained in the recorded fluorescence Mueller matrix of the organic polymer material provided a useful way to control the spectral intensity of emission by using pre- and post-selection of polarization states. The observation was based on the assumption that the longer lifetime of the excited dipolar orientation is attributed to the compactness of the film.

Barbiturate derived amphiphilic homopolymers: synthesis, characterization, self-assembly and anticancer drug delivery.

Aim: Our aim was to synthesis and characterization of amphiphilic norbornene-derived thiobarbiturate homopolymers (NDTH 1-4) for drug delivery. Methods: Ring-opening metathesis polymerization technique was used to prepare a series of homopolymers. The hydrophobicity is introduced by increasing the number of carbon chains ([-CH2-]n; n = 1, 2, 3 & 4) in between norbornene backbone and thiobarbiturate species. Results: These vesicular aggregates have been used as anticancer Doxorubicin drug delivery vehicles at the acidic (5.5) and physiological (7.4) pHs. Confocal laser-scanning microscopy has demonstrated that the drug-loaded vesicles are easily internalized into living cells. Conclusion: Amphiphilic norbornene-derived thiobarbiturate homopolymer assemblies showed efficient nanocarrier for effective anticancer drug delivery.

Enhancing antimycobacterial activity of isoniazid and rifampicin incorporated norbornene nanoparticles.

Background: Tuberculosis (TB) has been identified in skeletons over 6000 years old and still remains as the most prevalent infectious disease in the world; thus, there is a need for development of new drugs or tuning of old drugs. Nanotechnology, an advanced technology, plays a vital role in research for the diagnosis and treatment of TB, thus preventing adverse effects and drug resistance. The objective of this study was to enhance the antimycobacterial activity of isoniazid- (INH) and rifampicin (RIF)-incorporated norbornene (NOR) nanoparticles in comparison with plain INH and RIF without nanoparticles. Methods: Norbornene-polyethylene glycol - Isoniazid copolymer (NOR-PEG-INH) and norbornene polyethylene rifampicin Co polymer (NOR-PEG-RIF) were used for this study. The percentage of INH and RIF in NOR nanoparticles was 35% and 74%, respectively. Mycobacterium growth indicator tube containing Middlebrook 7H9 broth, the liquid medium, was used to analyze in vitro activity of the NOR-based drug and the plain drug. Minimum inhibitory concentration (MIC) of the drugs was determined from H37Rv control strain of mycobacterium TB (MTB). Results: The dosage of INH and RIF is minimal in the combination form with the NOR nanoparticles compared to the plain INH and RIF. The results indicate that the minimum concentration of NOR-PEG-INH and NOR-PEG-RIF required inhibiting H37Rv strain of MTB was 0.05 µg/ml and 0.5 µg/ml, respectively. The results were similar to plain INH and RIF MIC. Conclusion: Low dosage of INH and RIF along with NOR nanocarrier has similar activity to that of INH and RIF; thus this is expected to reduce adverse effects and NOR did not alter the functional activity of INH and RIF, thus becoming eligible for the newer drug carrier in TB treatment.

Iron(III) Coordinated Polymeric Nanomaterial: A Next-Generation Theranostic Agent for High-Resolution T1-Weighted Magnetic Resonance Imaging and Anticancer Drug Delivery.

Theranostic-based nanomedicine plays a crucial role in the field of cancer therapy. This is due to having the capability to combine both therapy and diagnosis together in a single system. Herein a new class of metal-ligand-based nanocarrier in a norbornene backbone has been designed as a theranostic system. Fe3+-terpyridine complex (Fe-Tpy) has been used here as T1 contrast agent for high-resolution MR imaging, and hydrazone-linked doxorubicin is used for effective pH-responsive delivery. Polyethylene glycol functionalized with a folic acid (peg folate) motif is used to make the entire polymeric system dispersible in water for longer retention and site-specific therapy. All these specialty functional groups are anchored in a single system by using the ring-opening metathesis polymerization (ROMP) technique under the norbornene backbone. Relaxivity study and 1D image experiments have shown the utility of Fe-Tpy complex as an effective T1 contrast agent. In vitro studies are performed to confirm the promising potentiality of the nanocarrier as the efficient nanotheranostic system in prostate cancer.

NiFe2O4/Poly(1,6-heptadiyne) Nanocomposite Energy-Storage Device for Electrical and Electronic Applications.

In present study, we have synthesized intrinsically conductive poly(1,6-heptadiynes) via cyclopolymerization technique, and further it is composited with the NiFe2O4 to fabricate pellet for electrical and electronic applications. The synthesized polymer I-V characteristics were obtained by two-probe measurement technique. The results suggest that the high current density of the synthesized polymer was in the range of 1.2 × 10-5-3.1 × 10-5 S/cm, which attributes to the potentially induced hoping charge-carrier mechanism within the conjugated poly(1,6-heptadiynes). NiFe2O4 and NiFe2O4/poly(1,6-heptadiynes) composite pellets were fabricated by utilizing hydraulic pelletizer. The sample's electrical measurements were performed via broad-band dielectric impedance spectroscopy, wherein the composite permittivity was about ε = 45 (100 Hz to 10 kHz), which attributes to the NiFe2O4 and poly(1,6-heptadiynes) phases; further, this describes the capacitance, which improved from 0.3 to 0.1 pf at 1 kHz. Also, these results suggest the reduced equivalent series resistance (72.1-1 MHz), which attributes to the incorporated intrinsically conducting poly(1,6-heptadiynes). Thus, the reduced dissipation factor (DF = 0.0032) was observed from impedance characteristics of a nanocomposite. Moreover, the improved Q-factor was observed, which was about 8.1-310 at 1 kHz. The resistance and capacitance time constant was also computed to be about 0.29 µs at 1 kHz for NiFe2O4/poly(1,6-heptadiynes) nanocomposite. Furthermore, the nanocomposite-enabled capacitor gravimetric energy density and power densities were calculated to be about 0.00575 mJ/g and 9.91 W/g, respectively. Additionally, thermal threatening, that is, heat generated within the capacitor, P loss is also estimated for the nanocomposite capacitor, which improved from 0.0006 to 8.9 × 10-6, and these results suggest improved nanocomposite thermal stability. Further, the delineated quantities were compared to the commercially available configurations of tantalum hybrid capacitors and Al and Ta electrolytic capacitors, including carbon electrochemical capacitors, which suggest that the reported nanocomposites could be a suitable candidate for electrical and electronic applications.

Synthesis of Norbornene Derived Helical Copolymer by Simple Molecular Marriage Approach to Produce Smart Nanocarrier.

A novel library of norbornene derived helical copolymer has been synthesized through the coupling of two homopolymers via Molecular Marriage Approach. The helicity is governed by the non-covalent interactions like hydrogen bonding, π-π stacking and the influence of hydrophobic and hydrophilic motifs. The detailed characterization of the copolymer (Copoly 1) has been provided and the super structures are confirmed through dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The observed size of the aggregates was about 200 nm. The density functional theory (DFT) is favorably supported for the formation of proposed structure of Copoly 1. Circular dichroism (CD) measurement has confirmed the one handed helical structure of the copolymer. Reservoir capability of this pH responsive polymer (Copoly 1) to encapsulate anti-cancer drug doxorubicin (DOX) warrants its potential applications in the field of bio-medical sciences.

Engineering Camptothecin-Derived Norbornene Polymers for Theranostic Application.

A multifunctional stimuli-responsive nanotheranostic agent provides huge benefits in nanomedicine by combining both the diagnostic agent and the drug molecule in a single system. This nanosystem is capable of doing multiple tasks, for example, diagnosis, drug delivery, and monitoring the therapeutic response. Hence, theranostic agents are expected to play a significant role in personalized medicine. Herein, a new class of nanotheranostic agents, Pnr-Cbt-Cpt-Pg-Bn, is proposed for the effective delivery of camptothecin. This new class of polymer has been functionalized with a superparamagnetic norbornene cobalt unit for its use in magnetic resonance imaging (MRI). The NMR one-dimensional image confirms the MRI capability of this nanotheranostic agent. This is further modified with the poly(ethylene glycol)-biotin moiety for biocompatibility and site-specificity. The uniqueness of the design is confirmed by an in vitro study where a greater uptake of the nanotheranostic agent is observed when compared with free drugs. Hence, this new class of copolymer shows improved potential as nanotheranostic agents in drug delivery.

Unique Design of Porous Organic Framework Showing Efficiency toward Removal of Toxicants.

This report deligates about the creation of porous polymeric organic framework (POF) from dialkynes and poly(alkyne) with their discovery as an efficient set of purifier. POF showed efficient physisorption for dyes-fluorescein and rhodamine B. The material POF selectively released rhodamine B and not fluorescein. The material was recyclable over number of cycles during the adsorption-release cycle. Moreover, the thiol-functionalized POF expectedly showed chemisorption for mercury. Therefore, the prime attractive cause for such a material is its ability to recycle as well as its thiol functionalization toward the removal of heavy metal such as mercury.

Engineering a New Class of Multiarm Homopolymer for Sustainable Drug Delivery.

The first example of simple nanoaggregates, self-assembled from a new class of polymer has been explored. The synthesis and characterization of polyethylene glycol and doxorubicin attached to a 1,6-heptadiyne derivative (Macromonomer) are clearly described. Macromonomer is polymerized via olefin metathesis living cyclopolymerization method using the Grubbs-Hoveyda catalyst to produce a water-soluble Dox-Peg-Rcp-Fmoc polymer. All of the monomers and polymers are carefully characterized by GPC and 1H NMR spectroscopy. Fmoc deprotection of the Dox-Peg-Rcp-Fmoc polymer is carried out to produce the Dox-Peg-Rcp polymer. The newly designed Dox-Peg-Rcp polymer shows nanoaggregation in water. In addition to that, they are soluble in water as well as biological media. The drug release profile at mild acidic condition shows the importance of having ester linker. CLSM images of Dox-Peg-Rcp nanoaggregates clearly show the efficient internalization into the living cells. MTT assays of Dox-Peg-Rcp nanoaggregates show that these nanoaggregates have a greater anticancer efficacy. To the best of our knowledge, this is the first report on water-soluble polyacetylenes for biological/drug delivery applications.