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The naturally occurring polyphenolic compound curcumin has shown various medicinal and therapeutic effects. However, there are various challenges associated with curcumin, which limits its biomedical applications, such as its high degradation rate and low aqueous solubility at neutral and alkaline pH. In the present study, efforts have been directed towards trying to resolve such issues by encapsulating curcumin inside the micelles formed by imidazolium-based surface-active ionic liquid (SAIL). The shape and size of the micelles formed by the SAIL have been characterized by using DLS analysis as well as TEM measurements. The photo-physics of curcumin in the presence of ionic liquid (IL) and also with the addition of salt (NaCl) has been explored by using different optical spectroscopic tools. The time-dependent absorption studies have shown that there is relatively higher suppression in the degradation rate of curcumin after encapsulation by the imidazolium-based SAIL in an aqueous medium. The TCSPC studies have revealed that there is deactivation in the nonradiative intramolecular hydrogen transfer process of curcumin in the presence of IL micelles as well as with the addition of salt. Furthermore, the time-dependent fluorescence anisotropy measurement has been carried out to figure out the location of curcumin inside the micellar system. In order to correlate all experimental findings, density functional theory (DFT) and classical molecular dynamics (MD) simulations at neutral pH media have been performed. It has been found that the van der Waals force of interactions plays a major role in the stabilization of curcumin in the micelles rather than the coulombic forces. It also has been observed that the van der Waals interactions remain unaffected in the presence of salt. However, as revealed by the MD simulation results, the micelles are found to be more compact in size after the addition of salt. The RMSD results show that the micelles formed by the SAIL achieve greater stability after a particular time constraint. Our results have divulged that the SAIL could act as a promising drug delivery system.

Objective: Nonthermal plasma at atmospheric condition using dielectric barrier discharge (DBD) is reported to be useful in many applications. Here, we have developed a strategy to generate nonthermal atmospheric plasma (NTAP) at ambient conditions for potential biomedical applications. Methods: We have explored the active ingredients of the nonthermal plasma using atomic emission spectroscopy. The potential mechanism of the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from the generated plasma for therapeutic use has been demonstrated. Major results: The antimicrobial efficacy of the nonthermal plasma application to model Staphylococcus aureus and Candida albicans biofilms has been investigated. Our detailed electron microscopic studies followed by biochemical investigation reveal the mechanism of bacterial/fungal deactivation process. The nuclear magnetic resonance (NMR) studies on the live cell of C . albicans before and after NTAP treatment clearly conclude the disruption of cellular envelope leading to necrosis as evidenced by fluorescence-assisted cell sorting (FACS) studies. Conclusions: The proposed NTAP setup may find relevance in novel strategies in bacterial and fungal biofilm destruction in the future development of nonfluid hand sanitization.

Recently, metal exchange (transmetalation) techniques have become popular for the post-synthesis modification of metal organic complexes (MOCs). Here, we have explored the possibility of toxic metal ion (mercury (Hg)) exchange from a model polyphenol, curcumin, which is a very important food additive, using a much less toxic counterpart (copper). While the attachment of different metals on the polyphenol was confirmed using a picosecond resolved fluorescence technique, the surface plasmon resonance (SPR) band of the Ag nanoparticle (NP) was employed as a tool to detect uncoupled Hg ions in aqueous media. Furthermore, a microscopic understanding of the experimental observations was achieved through density functional theory (DFT) based theoretical studies. The presence of Cu ions in the vicinity of Hg–curcumin, upon ground state optimization, was observed to extrude most of the Hg from the curcumin complex and replace its position in the complex. The study may find relevance in the development of a purification strategy for food additives heavily contaminated with toxic metals.

In this work, we have successfully synthesized a bimetallic (Zinc and Cobalt) Zeolitic Imidazolate Framework (Zn50Co50-ZIF), a class in a wider microporous Metal-Organic Framework (MOF) family. The synthesized nanostructures maintain both water stability like ZIF-8 (solely Zn containing) and charge transfer electronic band in the visible optical spectrum as ZIF-67 (solely Co containing). Crystal structure from XRD, high resolution transmission electron microscopy (HRTEM) followed by elemental mapping (EDAX) confirm structural stability and omnipresence of the metal atoms (Zn and Co) across the nanomaterial with equal proportion. Existence of charge transfer state consistent with ZIF67 and intact ultrafast excited state dynamics of the imidazolate moiety in both ZIF-8 and ZIF-67, is evidenced from steady state and time resolved optical spectroscopy. The thermal and aqueous stabilities of Zn50Co50-ZIF are found to be better than ZIF-67 but comparable to ZIF-8 as evidenced by solubility, scanning electron microscopy (SEM) and XRD studies of the material in water. We have evaluated the photoinduced ROS generation by the mixed ZIF employing dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. We have also explored the potentiality of the synthesized material for the alternate remediation of methicillin resistant Staphylococcus aureus (MRSA) infection through the photoinduced reactive oxygen species (ROS) generation and methylene blue (MB) degradation kinetics.

Nanoscale science and nanotechnology are expected to bring about revolutionary advances in the agrochemical industry. Smart delivery of micronutrients enabling sustained release is one such innovative approach to combat the poor nutrient uptake efficiency of conventional micronutrient sources. Herein, we report a bottom-up surface fabrication strategy to modify nanosized zinc oxide (ZnO NPs) surfaces at an atomic scale for sustained release of Zn micronutrients. A large sized environmentally relevant macromolecule humic acid (HA) and a comparatively smaller biologically pertinent citrate ligand were used to functionalize ZnO NPs (30 nm), and the resultant nanohybrids were characterized using electron microscopy, diffraction, and spectroscopic techniques. Functionalization with citrate ligand turns the NP smaller than its original size. The resultant modification in the dissolution characteristics of ZnO NPs leads to sustained release of Zn over a broad pH range. Functionalization with HA causes minimum al...

Multidrug resistance (MDR) of bacteria is a major threat to public health globally and its unprecedented increase calls for immediate alternative medical strategies. Antimicrobial photodynamic therapy (aPDT) offers alternative modalities to combat the growing MDR typically by means of targeted cellular internalization of a photosensitizer (PS) capable of producing photoinduced reactive oxygen species (ROS). However, aPDT is severely limited by the self-aggregation behavior and hydrophobicity of PS molecules, which significantly curbs its viability for clinical application. The present study reports the use of modified nanoscale metal-organic frameworks (NMOFs) encapsulating a hydrophobic PS drug squaraine (SQ) to enhance aPDT efficacy against drug-resistant planktonic bacteria and its biofilm for the first time. Zeolitic imidazolate framework (ZIF-8) NMOF nanocrystals are attached postsynthetically with SQ (designated as ZIF8-SQ) and the resultant drug-doped NMOF is characterized by TEM, FESEM, PXRD, Raman spectroscopy, UV-vis spectroscopy, and steady-state and time-resolved fluorescence techniques. The microporous structures of ZIF-8 behave as molecular cages ceasing the self-aggregation of hydrophobic SQ. In addition, the formulated ZIF8-SQ produces cytotoxic ROS under red-light irradiation (650 nm) in a pH sensitive way primarily due to molecular level interaction and charge separation between ZIF-8 and SQ depicting a dual-stimuli-responsive nature. Most notably, ZIF8-SQ provides unparalleled aPDT action against methicillin-resistant

The properties of nanomaterials generated by external stimuli are considered an innovative and promising replacement for the annihilation of bacterial infectious diseases. The present study demonstrates the possibility of getting the antibiotic-like drug action from our newly synthesized nanohybrid (NH), which consists of norfloxacin (NF) as the photosensitive material covalently attached to the ZnO nanoparticle (NP). The synthesized NH has been characterized using various microscopic and spectroscopic techniques. Steady state fluorescence and time-correlated single photon counting (TCSPC)-based spectroscopic studies demonstrate the efficient electron transfer from NF to ZnO. This enhances the reactive oxygen species (ROS) production capability of the system. First principles density functional theory has been calculated to gain insight into the charge separation mechanism. To explore the electron densities of the occupied and unoccupied levels of NH, we have verified the nature of the electronic structure. It is observed that there is a very high possibility of electron transfer from NF to ZnO in the NH system, which validates the experimental findings. Finally, the efficacy of NH compared to NF and ZnO has been estimated on the in vitro culture of E. coli bacteria. We have obtained a significant reduction in the bacterial viability by NH with respect to control in the presence of light. These results suggest that the synthesized NH could be a potential candidate in the new generation alternative antibacterial drugs. Overall, the study depicts a detailed physical insight for nanohybrid systems that can be beneficial for manifold application purposes.

The drug resistance of bacteria is a significant threat to human civilization while the action of antibiotics against drug-resistant bacteria is severely limited owing to the hydrophobic nature of drug molecules, which unquestionably inhibit its permanency for clinical applications. The antibacterial action of nanomaterials offers major modalities to combat drug resistance of bacteria. The current work reports the use of nano–metal-organic frameworks encapsulating drug molecules to enhance its antibacterial activity against model drug-resistant bacteria and biofilm of the bacteria. We have attached rifampicin (RF), a well-documented antituberculosis drug with tremendous pharmacological significance, into the pore surface of zeolitic imidazolate framework 8 (ZIF8) by a simple synthetic procedure. The synthesized ZIF8 has been characterized using the X-ray diffraction (XRD) method before and after drug encapsulation. The electron microscopic strategies such as scanning electron microscope and transmission electron microscope methods were performed to characterize the binding between ZIF8 and RF. We have also performed picosecond-resolved fluorescence spectroscopy to validate the formation of the ZIF8-RF nanohybrids (NHs). The drug release profile experiment demonstrates that ZIF8-RF depicts pH-responsive drug delivery and is ideal for targeting bacterial disease corresponding to its inherent acidic nature. Most remarkably, ZIF8-RF gives enhanced antibacterial activity against methicillin-resistant Staphylococcus aureus bacteria and also prompts entire damage of structurally robust bacterial biofilms. Overall, the present study depicts a detailed physical insight for manufactured antibiotic-encapsulated NHs presenting tremendous antimicrobial activity that can be beneficial for manifold practical applications.

Implementation of near infrared radiation (NIR) active drugs in photodynamic therapy (PDT) is considered as a highly promising tool in therapeutic application. Because of its strong NIR absorbance, indocyanine green (ICG) has become an attractive choice in emerging photo-theranostics. ICG generates singlet oxygen as well as shows photothermal effect under NIR irradiation. However, ICG is unable to produce sufficient amount of others types of reactive oxygen species (ROS) such as superoxide, hydroxyl radical. But, its ability of singlet oxygen generation under NIR irradiation is arrested by its tendency to aggregate in aqueous medium. Because of this limitation, it shows better effectiveness in photothermal therapy compare to it’s action as a photodynamic agent. Herein, we have addressed to overcome this limitation via the fabrication of zinc oxide (ZnO) based ICG-ZnO nanohybrid which provides lesser H-aggregation between ICG molecules on its surface and yield significantly greater amount of ROS relative to ICG upon photoexcitation, due to excited state electron transfer from ICG to ZnO. Also, this surface functionalization prevents aggregation of ICG in water significantly. Classical MD simulation shows the dimeric structure of ICG breakes down on ZnO surface which corroborates results from the aggregation study in water. Density functional theory (DFT) along with time-dependent DFT studies elucidate that upon photoexcitation electron transfer takes place from the higher energy orbital of ICG to the conduction band of ZnO. The greater efficiency in ROS generation by the ICG-ZnO nanohybrid than ICG or ZnO demonstrates remarkable antimicrobial activity against gram-negative bacteria E. coli. Overall, the present study highlights the scope of developing ICG-ZnO nanohybrid as a highly efficient NIR agent for use in antibacterial photodynamic therapy.

Nanomaterials with antimicrobial properties triggered by external stimuli appear to be a promising and innovative substitute for the destruction of antibiotic-resistant superbugs as they can induce multiple disruptions in the cellular mechanism. This study demonstrates the use of squaraine (SQ) dye as the photosensitive material, activated in the near-infrared tissue-transparent therapeutic window. The dye has been covalently attached to the ZnO nanoparticle surface, forming ZnO-SQ nanohybrids. The formation of the nanohybrids is confirmed using Fourier transform infrared and other optical spectroscopic methods. The photoinduced interfacial electron transfer process (as confirmed using the time-resolved fluorescence technique) from the excited state of SQ to the conduction band of ZnO is responsible for the greater reactive oxygen species (ROS) generation ability of the nanohybrid. The production of photoactivated ROS (especially singlet oxygen species) by ZnO-SQ provides remarkable antimicrobial action against clinically significant Staphylococcus aureus. Detailed investigations suggest synergistic involvement of cell membrane disruption and nanoparticle internalization followed by photoinduced intracellular ROS generation, which result in an unprecedented 95% bacterial killing activity by the nanohybrid. Moreover, the efficacy of the nanohybrid for disruption of bacterial biofilms has been examined. The electron microscopic images suggest significant bacterial cell death following structural alteration and reduced adherence property of the biofilms. Nanodimension-driven greater internalization of ZnO-SQ followed by an improved dissolution of ZnO in an acidic environment of the biofilm as well as red-light-driven interfacial charge separation and ROS generation improves the efficacy of the material for biofilm destruction. An artificial medical implant mimicking titanium sheets coated with ZnO-SQ depicts light-triggered disruption in the adherence property of matured biofilms. The cytotoxicity and hemolysis assays show inherent biocompatibility of the photoactive nanohybrid. This study is notably promising for the treatment of life-threatening drug-resistant infections and eradication of biofilms formed within artificial implants.

Recently, metal exchange (transmetalation) techniques have become popular for the post-synthesis modification of metal organic complexes (MOCs). Here, we have explored the possibility of toxic metal ion (mercury (Hg)) exchange from a model polyphenol, curcumin, which is a very important food additive, using a much less toxic counterpart (copper). While the attachment of different metals on the polyphenol was confirmed using a picosecond resolved fluorescence technique, the surface plasmon resonance (SPR) band of the Ag nanoparticle (NP) was employed as a tool to detect uncoupled Hg ions in aqueous media. Furthermore, a microscopic understanding of the experimental observations was achieved through density functional theory (DFT) based theoretical studies. The presence of Cu ions in the vicinity of Hg-curcumin, upon ground state optimization, was observed to extrude most of the Hg from the curcumin complex and replace its position in the complex. The study may find relevance in the development of a purification strategy for food additives heavily contaminated with toxic metals.

The efficacy and toxicity of drugs depend not only on their potency but also on their ability to reach the target sites in preference to non-target sites. In this regards destabilization of delivery vehicles induced by light can be an effective strategy for enhancing drug delivery with spatial and temporal control. Herein we demonstrate that the photoinduced isomerization from closed (hydrophobic) to open isomeric form (hydrophilic) of a novel DHI encapsulated in liposome leads to potential light-controlled drug delivery vehicles. We have used steady state and picosecond resolved dynamics of a drug 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor the efficacy of destabilization of liposome in absence and presence UVA irradiation. Steady state and picosecond resolved polarization gated spectroscopy including the well-known strategy of solvation dynamics and Förster resonance energy transfer; reveal the possible mechanism out of various phenomena involved in destabilization of liposome. We have also investigated the therapeutic efficacy of doxorubicin (DOX) delivery from liposome to cervical cancer cell line HeLa. The FACS, confocal fluorescence microscopic and MTT assay studies reveal an enhanced cellular uptake of DOX leading to significant reduction in cell viability (∼40%) of HeLa followed by photoresponsive destabilization of liposome. Our studies successfully demonstrate that these DHI encapsulated liposomes have potential application as a smart photosensitive drug delivery system.

Curcumin pyrazole derivatives have already been extensively studied as potent drugs in various biological fields but the information about their fundamental physical parameters is still somewhat limited. Therefore, the study of the photophysical behaviour of pyrazole derivatives of curcumin in various solvents is a very interesting and an important research area that necessarily needs to be explored in order to understand its biological efficacy. Herein, the photophysics of stable and pharmaceutically active curcumin pyrazole derivative (CPD) and curcumin phenyl pyrazole derivative (CPPD) has been studied in various solvent environments. For the investigation of photophysical properties, various spectroscopic techniques have been utilized. Steady state spectroscopic results have revealed that the excited state of both the derivatives is largely affected by changing the polarity of the medium. The molar extinction coefficient (e) for CPD and CPPD has also been determined in various solvents. From the measurement of Stokes shift values for wide range of solvents, it could be concluded that there is difference in the dipole moment of the excited state and the ground state of both the molecules. The Stokes shift values for both the derivatives were found to be correlated linearly with the normalized molar transition energy ( E T N ) of solvents with exceptions in case of polar protic solvents. This indicates that H- bonding might play a major role in the solution phase. The difference in the dipole moment of ground state and excited state of CPD and CPPD were calculated as around 5.23 D and 5.41 D. Further, using multiple regression analysis, the solute -solvent interactions were characterized as specific and non-specific. The low quantum yields obtained in polar protic solvents revealed that the positive solvatokinetic effect could take place in these solvents. The results of TCSPC study showed that the process of deactivation of the excited state of these derivatives is very slow in the presence of acetonitrile, DCM and non-polar solvents. A very fast decay of excited state of both the derivatives has been observed in the case of polar protic solvents. This could be due to the presence of strong H-bonding between the derivatives and these solvents which could result in the deactivation of excited states via non-radiative pathway.

Appropriate localization of a drug and its structure/functional integrity in a delivery agent essentially dictates the efficacy of the vehicle and the medicinal activity of the drug. In the case of a phototherapeutic drug, its photoinduced dynamics becomes an added parameter. Here, we have explored the photoinduced dynamical events of a model phototherapeutic drug psoralen (PSO) in a potential delivery vehicle called an ethosome. Dynamic light scattering confirms the structural integrity of the ethosome vehicle after the encapsulation of PSO. Steady state and picosecond resolved polarization gated spectroscopy, including the well-known strategy of solvation and Förster resonance energy transfer, reveal the localization of the drug in the vehicle and the environment in the proximity of PSO. We have also investigated the efficacy of drug delivery to various individual bacteria (Gram-negative: Escherichia coli; Gram-positive: Staphylococcus aureus) and bacterial biofilms. Our optical and electron microscopic studies reveal a significant reduction in bacterial survival (∼70%) and the destruction of bacterial adherence following a change in the morphology of the biofilms after phototherapy. Our studies are expected to find relevance in the formulation of drug delivery agents in several skin diseases and biofilm formation in artificial implants.

Structural defects of wide band gap semiconductors play important role in their functionality. Defect mediated recombination of photoinduced electron-hole pair in the semiconductors for their photocatalytic activities, is detrimental. In the case of ZnO nanostructures, radiative recombination upon band-gap photo-excitation (3.37 eV) originated from different surface defects (mainly Oxygen vacancies at 2.50 eV (V + ) and 2.25 eV (V ++ ) with respect to valance and conduction bands respectively) of crystal lattice, acquires immense interest for both fundamental scientific point of view and for the betterment of their manifold applications. The present work indicates that for transition metal semiconducting oxides, use of anionic attachment like Cl − as surface defect healer proves to be more useful for photocatalytic application than bulk doping using cationic dopant like Mn. ZnO NPs of different sizes (5 nm and 30 nm) are synthesized via precipitation method and allowed to interact with chloride ions in aqueous solution. A variety of electron microscopy and picosecond resolved spectroscopic techniques have been employed to study the role of chloride ions for the enhanced photoinduced charge separation in the aqueous environments. Our first principles density-functional calculations for ZnO nanoclusters with surface oxygen vacancy indicate introduction of trap states within the band gap of the nanoclusters. These states effectively confine the photoinduced electrons and thus essentially reduce the photocatalytic yield with respect to pristine ZnO. However, upon Cl − attachment to the defect states, the energy of the trap states were found to be healed, recovering the efficacy of reactive oxygen species (ROS) generation in the aqueous solution. We have also impregnated Mn 2+ ions to the ZnO lattice using precipitation method in solution phase. The DFT calculation on the Mn 2+ ion impregnated ZnO lattice reveals more defect states compare to that of pristine lattice. The rate of electron recombination is found to be much faster through non-radiative pathway (ground state recovery), leading to a decrease in photocatalytic activity in the case of Mn-doped ZnO. Attachment of Cl − to the Mn-doped ZnO partially recovers the ROS generation, which is consistent with healing of deep trap states. The present work is anticipated to provide a new insight into the surface defect modulation of ZnO in potential photocatalysis application.

The immense pharmacological relevance of the herbal medicine curcumin including anti-cancer and anti-Alzheimer effects, suggests it to be a superior alternative to synthesised drugs. The diverse functionalities with minimal side effects intensify the use of curcumin not only as a dietary supplement but also as a therapeutic agent. Besides all this effectiveness, some recent literature reported the presence of deleterious heavy metal contaminants from various sources in curcumin leading to potential health hazards. In this regard, we attempt to fabricate ZnO based nanoprobes to detect metal conjugated curcumin. We have synthesized and structurally characterized the ZnO nanorods (NR). Three samples namely curcumin (pure), Zn-curcumin (non-toxic metal attached to curcumin) and Hg-curcumin (toxic heavy metal attached to curcumin) were prepared for consideration. The samples were electrochemically deposited onto ZnO surfaces and the attachment was confirmed by cyclic voltammetry experiments. Moreover, to confirm a molecular level interaction picosecond-resolved PL-quenching of ZnO NR due to Förster Resonance Energy Transfer (FRET) from donor ZnO NR to the acceptor curcumin moieties was employed. The attachment proximity of ZnO NR and curcumin moieties depends on the size of metals. First principles analysis suggests a variance of attachment sites and heavy metal Hg conjugated curcumin binds through a peripheral hydroxy group to NR. We fabricated a facile photovoltaic device consisting of ZnO NR as the working electrode with Pt counter electrode and iodide-triiodide as the electrolyte. The trend in photocurrent under visible light illumination suggests an enhancement in the case of heavy metal ions due to long range interaction and greater accumulation of charge at the active electrode. Our results provide a detailed physical insight into interfacial processes that are crucial for detecting heavy-metal attached phytomedicines and are thus expected to find vast application as sensors for the detection of selective metal contaminants.

Near-infrared (NIR) light harvesting has enormous importance for different potential applications in the modern era of research. Some NIR cyanine dyes such as IR820 have achieved great success in energy harvesting and cancer therapy. However, their action is limited for low photostability, considerable thermal degradation, short circulation times, and nonspecific biodistribution. Our present study is an attempt to overcome such limitations by attaching a model cyanine dye IR820 with ZnO nanoparticles. We prepared an IR820-ZnO nanohybrid and characterized it using microscopic and optical spectroscopic tools. Thermogravimetric analysis depicted greater thermal stability of the IR820-ZnO nanohybrid compared to free dye. We explored the enhancement in the photostability of IR820 upon nanohybrid formation. We detected generation of photoinduced reactive oxygen species (ROS) such as superoxide, singlet oxygen, and so forth using appropriate molecular probes. The formation of IR820-ZnO nanohybrid reduced production of photoinduced singlet oxygen. However, it revealed an alternative trend in overall ROS formation (increases total ROS) under red light illumination. To correlate the enhanced photostability of IR820 on the ZnO surface, we explored excited-state dynamical processes at the interface in nanohybrids. We illustrated the photoinduced excited-state electron-transfer process from the lowest unoccupied molecular orbital of IR820 to the conduction band of ZnO. This photoelectron-transfer process enhances the production of ROS and decreases the formation of singlet oxygen that altogether leads to improvement in photostability and overall activity. A quencher of singlet oxygen sodium azide (NaN3) was used to further confirm the direct association of singlet oxygen generation with the photostability issue of IR820. Also, ZnO is able to deliver the dye selectively in acidic environment, which suggests its diseased site-specific targeted activity. Our results provide promising improvement for potential use of IR820 through formation of a nanohybrid that could be translated for other NIR cyanine dyes.

The present work aims to decipher the photophysics of a β-diketo modified curcumin analog named isoxazole derivative of curcumin (IOC). IOC itself happens to be a potential drug molecule possessing numerous biological applications such as; anti-cancer, anti-malarial, anti-Alzheimer’s, anti-Parkinson’s etc. Herein, the photophysical properties of IOC have been explored in various sets of solvents. In order to investigate, steady state and time resolved spectroscopy have been utilized as a tool. To elucidate the experimental observations at molecular level, electronic structure calculations with density functional theory (DFT) as well as classical molecular dynamics (MD) simulations in explicit solvents have been deployed. The DFT has established that the most stable ground state electronic structure of the IOC molecule is the all trans- planar conformation where the conjugated pi-electrons are delocalized over the entire molecule. The MD simulations have provided an insight into the specific and non-specific interactions with the solvent molecules. Steady state spectroscopic techniques have shown that both the absorption and emission maxima experienced a traditional red shift upon increase in the solvent polarity. The absorption maxima for IOC got red shifted from 332 nm in hexane to 344 nm in DMSO. However, the red shift in the emission maxima is more pronounced than that of absorption maxima starting from 356 nm in hexane to 431 nm in water. The value of molar extinction coefficient has also been determined for IOC in different solvents from the concentration dependent absorption spectra. The time correlated single photon counting (TCSPC) data has revealed that the excited state of IOC molecule could relax via three probable pathways. Also, the overall process of decay of the excited state is comparatively slower in case of non-polar solvents. On the other hand, the fluorescence lifetime has been observed to be unusually low in case of dimethyl sulfoxide (DMSO) as compared to its other fellow polar aprotic solvents.

The efficiency of drug depends not only on its potency but also on its ability to reach the target sites in preference to non-target sites. In this regard, protein assembled nanocarrier is the most promising strategy for intracellular anti-cancer drug delivery. The key motive of this study is to fabricate biocompatible protein assembled nanocarrier conjugated photosensitizer system for stimuli-responsive treatment of lung carcinoma. Here, we have synthesized a unique nanohybrid of protein assembled gold nanoparticles (AuNPs), attaching a model photosensitizer, Protoporphyrin IX (PpIX) to the protein shell of the nanoparticles (NPs) imparting an ideal drug-carrier nature. Photo-induced alteration in hydrodynamic diameter suggests structural perturbation of the nanohybrid which in terms signifies on-demand drug delivery. The drug release profile has been further confirmed by using steady-state fluorescence experiments. AuNP-PpIX showed excellent anti-cancer efficiency upon green light irradiation on lung adenocarcinoma cell line (A549) through intracellular reactive oxygen species (ROS) generation. The cellular morphological changes upon PDT and internalization of nanohybrid were monitored using confocal laser scanning microscope. This anti-cancer effect of nanohybrid was associated with apoptotic pathway which was confirmed in the flow cytometric platform. The developed nanomedicine is expected to find relevance in clinical anti-cancer PDT models in the near future.

In general, biological macromolecules require significant dynamical freedom to carry out their different functions, including signal transduction, metabolism, catalysis and gene regulation. Effectors (ligands, DNA and external milieu, etc) are considered to function in a purely dynamical manner by selectively stabilizing a specific dynamical state, thereby regulating biological function. In particular, proteins in presence of these effectors can exist in several dynamical states with distinct binding or enzymatic activity. Here, we have reviewed the efficacy of ultrafast fluorescence spectroscopy to monitor the dynamical flexibility of various proteins in presence of different effectors leading to their biological activity. Recent studies demonstrate the potency of a combined approach involving picosecond-resolved Forster resonance energy transfer, polarisation-gated fluorescence and time-dependent stokes shift for the exploration of ultrafast dynamics in biomolecular recognition of various protein molecules. The allosteric protein-protein recognition following differential protein-DNA interaction is shown to be a consequence of some ultrafast segmental motions at the C-terminal of Gal repressor protein dimer with DNA operator sequences OE and OI. Differential ultrafast dynamics at the C-terminal of λ-repressor protein with two different operator DNA sequences for the protein-protein interaction with different strengths is also reviewed. We have also systemically briefed the study on the role of ultrafast dynamics of water molecules on the functionality of enzyme proteins alpha-chymotrypsin and deoxyribonuclease I. The studies on the essential ultrafast dynamics at the active site of the enzyme alpha-chymotrypsin by using an anthraniloyl fluorescent extrinsic probe covalently attached to the serine-195 residue for the enzymatic activity at homeothermic condition has also been reviewed. Finally, we have highlighted the evidence that a photoinduced dynamical event dictates the molecular recognition of a photochromic ligand, dihydroindolizine with the serine protease alpha-chymotrypsin and with a liposome (L-a-phosphatidylcholine).

Riboflavin (Rf) is a class of important vitamins (Vitamin B2) and a well-known antioxidant. Here we have synthesized nanohybrids of Rf with a number of inorganic nanoparticles (NPs); namely zinc oxide (ZnO), titanium oxide (TiO2), aluminum oxide (Al2O3) and gold NPs of similar sizes. While high resolution transmission electron microscopy (HRTEM) confirms integrity and sizes of the NPs, intactness of the molecular structure of the drug Rf is revealed from absorption and steady-state emission spectra of the drug in the nanohybrid. Raman spectroscopy on the nanohybrids shows the nature of molecular complexation of the drug with the inorganic NPs. For the semiconductor and insulator NPs, the complexation is found to be noncovalent, however, a covalent attachment of the drug with the dangling bonds of metal atoms at the surface is observed. In order to investigate antioxidant activity of the nanohybrids, we have performed 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay of the nanohybrids in dark as well as under blue light irradiation. Whereas change of the antioxidant activity of the nanohybrids with respect to free riboflavin in the absence of light is observed to be insignificant, a drastic change in the activity in the case of TiO2 and ZnO in the presence of light is evident. No change in the case of Al2O3 and a significant decrease in the antioxidant activity for gold nanohybrids are also remarkable. Picosecond-resolved fluorescence studies on the nanohybrids reveal a molecular picture of the differential antioxidant activities. An ultrafast photoinduced electron transfer from Rf to ZnO and TiO2 are clearly evident from the corresponding fluorescence transients. We have compared the picosecond-resolved transients with that of Rf in the presence of a well-known electron acceptor benzoquinone (BQ) and found similar time scales. No temporal change in the fluorescence transient of riboflavin in Al2O3 nanohybrids compared to that of free Rf is observed indicating uneventful excited state relaxation of the nanohybrids. Nanosurface energy transfer (NSET) over Förster resonance energy transfer (FRET) is found to be the prevailing de-excitation mechanism in the case of gold nanohybrids, because of the strong spectral overlap between Rf emission and surface plasmon absorption of the gold NPs. Different excited state mechanisms as revealed from our studies are expected to be useful for the design of NP-sensitized drugs, which are reported sparsely in the literature.

The natural polyphenol curcumin and its metal coordinated complexes show obvious benefits in the medical therapies of cancer and several neurodegenerative diseases. On the other side their stability and bioavailability are critical issues. The present study is an attempt to address the stability and functionality of curcumin upon complexation with transition metal ions. We have synthesized and optically characterized metallo–curcumin complexes with Cu(II) and Zn(II). From femtosecond resolved upconversion studies an interaction at the molecular level is revealed based on an observed photoinduced electron transfer from curcumin to the metal ions. In order to investigate the antioxidant activity of the complexes, we have performed a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay in dark. The Cu(II)–curcumin complex exhibits an enhanced and recyclable activity, more pronounced compared to that of the Zn(II)–curcumin complex, which can be attributed to the weaker O–H bond present in the former case. In contrast, the Zn(II) complex has a higher solubility and stability in aqueous media than the Cu(II) complex. To address stability vs. functionality issues, we have suggested a facile method that enhances the solubility and stability of curcumin in aqueous media by metalation with Zn(II) and a successional replacement of Zn(II) in the complex by Cu(II) through a simple route to enhance the activity prior to its use. We have also used the complex in a model anti-bacteriological assay experiment where it shows significantly higher activity compared to pure curcumin. The dichlorofluorescin (DCFH) oxidation indicates an enhancement in ROS generation, which in turn is responsible for the enhanced antioxidative property of the Cu(II)–curcumin complex. Our results provide a promising method to use metallo–curcumin complexes in diverse biological applications.

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure exhibiting cytotoxic effects toward malignant cells. Hydrophobic nature of most photosensitizers used in PDT with lower light absorption ability restricts practical use of PDT. Herein, we have employed a squaraine drug (SQ) with 665 nm absorbance peak maxima as the photosensitizing agent and evaluate its photo-physical properties. The tendency of aggregation formation in aqueous media limits its practical usefulness. Thus, we have synthesised wide band gap semiconductor zinc oxide (ZnO) nanoparticles and functionalized the surface using squaraine molecules. The molecular cross-talking was evaluated using excited state fluorescence lifetime decay profiles and by employing Fӧrster resonance energy transfer (FRET) technique. The nanohybrids show improvement in three aspects compared to bare SQ molecule such as lesser aggregate formation in aqueous media, pH responsive precipitation of the drug and improvement of photo-induced reactive oxygen species (ROS) generation. Ultrafast dynamical study at the inorganic (ZnO) - organic (SQ) interface depicts presence of photo-induced charge transfer process at the junction which indeed improves the ROS generation capability. Finally, the photodynamic action has been evaluated in human breast cancer cell line MCF-7. The nanohybrids depict enhanced photo toxicity in cancer cell with loss of adherence and typical morphology of cancerous cell depicting controlled cell death. The present study employ characterisation of nanohybrids for potential use in PDT for cancer treatment.

The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease α-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo-controlled manner. Simultaneous binding of the well-known inhibitors 4-nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Förster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1-Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity.

Aim: To test the potential of orally administered citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs) as a therapeutic agent against hepatic fibrosis and associated chronic liver diseases. Materials & methods: C-Mn3O4 NPs were synthesized and the pH dependent antioxidant mechanism was characterized by in vitro studies. CCl4 intoxicated mice were orally treated with C-Mn3O4 NPs to test its in vivo antioxidant and antifibrotic ability. Results: We demonstrated ultrahigh efficacy of the C-Mn3O4 NPs in treatment of chronic liver diseases such as hepatic fibrosis and cirrhosis in mice compared with conventional medicine silymarin without any toxicological implications. Conclusion: These findings may pave the way for practical clinical use of the NPs as safe medication of chronic liver diseases associated with fibrosis and cirrhosis in human subjects., Lay abstract Hepatic fibrosis is a common response to chronic liver injury from a number of causes including alcohol, toxin, and persistent viral and helminthic infections, which may ultimately lead to hepatic carcinoma. Although billions of people are affected throughout the world, there is no drug available for treatment of this chronic disease. Here, in a preclinical study, we have shown that oral administration of citrate functionalized Mn3O4 nanoparticles can effectively reduce the extent of liver fibrosis in mice. We have also predicted the underlying therapeutic mechanism that involves mitochondria and antioxidant systems of the body., Graphical abstract

Metal-organic frameworks (MOFs) hold great promises in biotechnological application. MOFs have been shown as efficient carriers of therapeutic drugs. Yet MOFs have not been used for simultaneous drug delivery and efficacy enhancement. In this study, a mixed metal MOF copper (Cu2+)-doped zeolitic imidazolate framework-8 (Cu/ZIF-8) was applied for the first time for simultaneous increment of drug stability (through metalation with zinc (Zn2+)) and functionality (via complexation with Cu2+). Copper was introduced in the tetrahedral sites of ZIF-8 in reactions conducted with 25% and 10% Cu2+ by weight of Zn2+ and the reaction time, temperature and metal to ligand ratios were optimized to ensure minimum distortions of ZIF-8 crystallinity. Further experiments were conducted with ZIF-8 prepared by 25% of Cu2+. The as synthesized (Cu Zn (2-methyl imidazolate)2) crystals were loaded with curcumin following a facile route at room temperature. Spectroscopic study of Cur@Cu/ZIF-8 revealed the nature of interaction to be metal chelation with or without adsorption while picosecond-resolved spectroscopic measurement depicted greater charge separation in Cur@Cu/ZIF-8 than Cu/ZIF-8. Cu/ZIF-8 exhibits reasonably high drug loading capacity (22%) with exceptionally high efficiency (83%). Attachment with Cu/ZIF-8 increased the aqueous stability of curcumin by several orders of magnitude. Reactive oxygen species (ROS) generation was amplified due to combined interactions of Zn2+ and Cu2+ representing d10 and d9 electronic configurations respectively and enhanced bond breaking tendency of peripheral −O−H bond of curcumin molecule. Note worthily, Cur@Cu/ZIF-8 also exhibits greater anti-bacterial and anti-biofilm effects than free curcumin, a combination that is best suited for biomedical application.

Drug sensitization with various inorganic nanoparticles (NPs) has proved to be a promising and an emergent concept in the field of nanomedicine. Rose bengal (RB), a notable photosensitizer, triggers the formation of reactive oxygen species under green-light irradiation, and consequently, it induces cytotoxicity and cell death. In the present study, the effect of photoinduced dynamics of RB upon complexation with semiconductor zinc oxide NPs is explored. To accomplish this, we successfully synthesized nanohybrids of RB with ZnO NPs with a particle size of 24 nm and optically characterized them. The uniform size and integrity of the particles were confirmed by high-resolution transmission electron microscopy. UV/Vis absorption and steady-state fluorescence studies reveal the formation of the nanohybrids. ultrafast picosecond-resolved fluorescence studies of RB-ZnO nanohybrids demonstrate an efficient electron transfer from the photoexcited drug to the semiconductor NPs. Picosecond-resolved Forster resonance energy transfer from ZnO NPs to RB unravel the proximity of the drug to the semiconductor at the molecular level. The photoinduced ROS formation was monitored using a dichlorofluorescin oxidation assay, which is a conventional oxidative stress indicator. It is observed that the ROS generation under green light illumination is greater at low concentrations of RB-ZnO nanohybrids compared with free RB. Substantial photodynamic activity of the nanohybrids in bacterial and fungal cell lines validated the in vitro toxicity results. Furthermore, the cytotoxic effect of the nanohybrids in HeLa cells, which was monitored by MTT assay, is also noteworthy.

Aim: To test the potential of orally administered citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs) as a therapeutic agent against hepatic fibrosis and associated chronic liver diseases. Materials & methods: C-Mn3O4 NPs were synthesized and the pH dependent antioxidant mechanism was characterized by in vitro studies. CCl4 intoxicated mice were orally treated with C-Mn3O4 NPs to test its in vivo antioxidant and antifibrotic ability. Results: We demonstrated ultrahigh efficacy of the C-Mn3O4 NPs in treatment of chronic liver diseases such as hepatic fibrosis and cirrhosis in mice compared with conventional medicine silymarin without any toxicological implications. Conclusion: These findings may pave the way for practical clinical use of the NPs as safe medication of chronic liver diseases associated with fibrosis and cirrhosis in human subjects.