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1.
J Photochem Photobiol B ; 203: 111765, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31923806

RESUMO

A potential strategy has been demonstrated, for the first time, for switching the mode of delivery of drugs or small molecular systems from endogenous to exogenous, simply by engineering the chain length of micellar carriers. Ethidium bromide (EB) is exploited as the model drug which has been successfully delivered to natural DNA through endogenous and exogenous modes by tuning the chain length of anionic sodium n-alkyl sulfate micelles. ß-cyclodextrin (ß-CD) is exploited as an extrinsic stimulant for the exogenous delivery of EB to DNA. Multi-spectroscopic techniques involving absorption, emission, fluorescence anisotropy, fluorescence decay analysis, circular dichroism, DNA helix melting etc. have established tuning of the delivery mode between endogenous and exogenous. Differential binding affinity of the model drug with different micelles of varying chain length relative to that with DNA is capitalized to make the switching feasible. Although endogenous mode avoids external stimulant and associated problems, a regulation of the stimulant concentration makes the other mode controllable and quantitative. With appropriate choice of carrier micelle and modulation of this developed strategy can radically change the therapeutic research enabling one to take a control over the drug delivery mode to exploit the advantage of one or the other selectively, whenever required.


Assuntos
DNA/química , Portadores de Fármacos/química , Etídio/química , Micelas , Dicroísmo Circular , Polarização de Fluorescência , Desnaturação de Ácido Nucleico , beta-Ciclodextrinas/química
2.
Int J Pharm ; 565: 378-390, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31075437

RESUMO

Medicine is a natural companion of mankind in the present era for mere survival from the deadly diseases in ever-increasing polluted environments. Hence, in recent years, major focus of pharmaceutical, medicinal and biophysical research has been navigated in exploring and developing new and simple avenues to enhance the efficacy of the administered drugs on one hand and to get rid of, or at least reduce, the toxic side effects of the excess drugs accumulated in human body on the other. A potential approach to amplify the efficacy of the administered drug is to develop proficient targeted drug delivery systems (DDSs). This review provides an essence of some newly developed simple but prospective strategies on enhancing the efficacy of drugs/bioactive molecules exploiting various drug delivery systems like micelles, cyclodextrins, liposomes etc. to serve the purpose of targeted delivery towards DNA, by endogenous and/or exogenous means. Improved bio-availability and solubilization of ionic drugs within the less polar target regions from the bulk aqueous phase has also been achieved through the introduction of some physiologically permissible salts. In the other context, in vitro and in vivo studies demonstrate a simple technique for easy removal of the excess adsorbed drug molecules from the cell membranes/lipid bilayers by exploiting health-amiable supramolecular assemblies. In this review, we summarize the recent experimental findings, mostly from our lab, encompassing the development of simple biocompatible methods to enhance the benevolent role of drugs through their safe, effective and convenient administration. It also presents easy and effective means to remove the excess adsorbed drugs from human body to diminish their malign effects. These prospective approaches of drug delivery and excretion of drug molecules have promising roles to play from both physicochemical and pharmaceutical perspectives, ensuring enhanced bioavailability of drugs as well as disposing of drug-induced adverse side effects.


Assuntos
Sistemas de Liberação de Medicamentos , Tratamento Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Solubilidade , Resultado do Tratamento
3.
Biophys Chem ; 240: 70-81, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29913331

RESUMO

Molecular interactions and binding of probes/drugs with biomacromolecular systems are of fundamental importance in understanding the mechanism of action and hence designing of proactive drugs. In the present study, binding interactions of a biologically potent fluorophore, (E)-1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole (DSDP) with two serum transport proteins, human serum albumin and bovine serum albumin, have been investigated exploiting multi-spectroscopic techniques. The spectrophotometric and fluorometric studies together with fluorescence quenching, fluorescence anisotropy, urea induced denaturation studies and fluorescence lifetime measurements reveal strong binding of DSDP with both the plasma proteins. Going beyond the vast literature data mostly providing 1:1 probe-protein complexation, the present investigation portrays 2:1 probe-protein complex formation at higher relative probe concentration. A newer approach has been developed to have an estimate of the binding constants varying the concentration of the protein, instead of the usual practice of varying the probe. The binding constants for the 2:1 DSDP-protein complexes are determined to be 1.37 × 1010 M-2 and 1.47 × 1010 M-2 for HSA and BSA respectively, while those for the 1:1 complexation process come out to be 1.85 × 105 M-1 and 1.73 × 105 M-1 for DSDP-HSA and DSDP-BSA systems respectively. Thermodynamic analysis at different temperatures implies that the forces primarily involved in the binding process are hydrogen bonding and hydrophobic interactions. Competitive replacement studies with known site markers and molecular docking simulations direct to the possible locations and binding energies of DSDP with the two serum proteins, corroborating well with the experimental results.


Assuntos
Pirazóis/metabolismo , Soroalbumina Bovina/metabolismo , Albumina Sérica/metabolismo , Animais , Sítios de Ligação , Bovinos , Polarização de Fluorescência , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Ligação Proteica , Desnaturação Proteica , Estrutura Terciária de Proteína , Pirazóis/química , Albumina Sérica/química , Soroalbumina Bovina/química , Temperatura , Termodinâmica , Ureia/química
4.
J Phys Chem A ; 122(25): 5545-5554, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29878784

RESUMO

Photophysics of 9,9'-anthril have been investigated at room temperature and cryogen phase (77 K) exploiting steady state and time-resolved emission techniques together with quantum chemical calculations. Absorption spectra, emission spectra, and emission lifetimes of anthril have been recorded and analyzed in polar ethanol and nonpolar methylcyclohexane media. Both room temperature and cryogenic experiments reveal a single emission band upon excitation at the nπ* absorption band whereas on exciting the system at the ππ* band, dual emission bands have been observed. Characterization of these two fluorescence bands to be originating from near-trans and relaxed skew conformers have been made by monitoring their differential effect on varying the polarity of solvents. Similarly, two phosphorescence bands have been assigned to trans and cis geometries by looking at the change in the emission spectra in the two rigid matrixes of different polarity. Observation of a single isoemissive point in the time-resolved area normalized emission spectroscopy (TRANES) for both fluorescence and phosphorescence emissions unambiguously validates the coexistence of the two conformers in the excited singlet and triplet states, respectively. Qualitative quantum chemical calculations indicate that the S1 and T1 states are responsible for the dual fluorescence and phosphorescence bands. Effortless transitions from the higher excited singlet states (S3 or S2) to the lowest energy excited singlet (S1) state because of their energy proximity discard any possibility of S2 emission, consistent with two other 1,2-dicarbonyl compounds like α-furil and 2,2'-pyridil, while going in contrast to the observation of S2 emissions from benzil and α-naphthil. On the basis of the vivid photophysical studies on five probes in fluid media and 77 K glassy matrixes, we conclude that exhibition of the S2 emission for aromatic 1,2-dicarbonyl compounds is truly system dependent and not a general phenomenon for all the molecular systems in the series.

5.
ACS Appl Mater Interfaces ; 10(20): 17409-17418, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29697251

RESUMO

Luminescent materials possessing both the mechanoluminescence (MCL) and electroluminescence (EL) properties are the quest for sensing and optoelectronic applications. We report on the synthesis of a new tailor-made luminogen, 1,2-bis(4-(1-([1,1'-biphenyl]-4-yl)-2,2-diphenylvinyl)phenyl)-1,2-diphenylethene (TPE 5), using Suzuki coupling reaction with high yield. An aggregation-induced emission (AIE) active complex TPE 5 forms supramolecular spherical aggregates at the air-water interface of a Langmuir trough. As a consequence, a large enhancement of luminescence is obtained from the mono- and multilayer Langmuir-Blodgett films of TPE 5 owing to the AIE effect. The luminogen TPE 5 exhibits a reversible MCL response, displaying photoluminescence switching due to change in the crystalline states under external stimuli. The unique feature of luminescence enhancement upon aggregate formation is utilized for the fabrication of light-emitting diodes with low threshold voltage using supramolecular aggregates as the active layer. This work demonstrates an efficient strategy for obtaining controlled supramolecular aggregates of AIEgen with a potential in the dual applications of MCL and EL.

6.
J Photochem Photobiol B ; 173: 485-492, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28668517

RESUMO

Deoxyribonuclic acid (DNA) is the most relevant intracellular target for a wide variety of anticancer and antibiotic drugs. Elucidating the binding interaction of small bioactive molecules with DNA provides a structural guideline for designing new drugs with improved selectivity and superior clinical efficacy. In the present work interaction of a newly synthesized biologically relevant fluorophore, namely, (E)-1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole (DSDP) with calf thymus DNA (ctDNA) has been investigated vividly through a number of in vitro studies. Noteworthy modifications in the UV-Vis absorption and emission spectra reveal the formation of the probe-ctDNA complex. Several other spectroscopic experiments such as circular dichromism (CD), iodide induced quenching, competitive binding assay with known groove binder probe, 3-hydroxyflavone (3HF), time resolved fluorescence decay measurements, thermometric experiment in connection with the helix melting of ctDNA etc. unequivocally ascertain the groove binding interaction of DSDP with ctDNA. Determination of the thermodynamic parameters through temperature variation study implies the dominant role of hydrophobic interaction in the probe-DNA binding process. Inappreciable change in the CD spectrum of ctDNA with the addition of DSDP suggests that binding of the probe with the DNA does not lead to a significant modification in the DNA conformation. In-silico molecular docking simulation corroborates the experimental findings and depicts that DSDP favorably binds to the minor groove region of the biomacromolecule.


Assuntos
DNA/metabolismo , Simulação de Acoplamento Molecular , Pirazóis/metabolismo , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , DNA/química , Interações Hidrofóbicas e Hidrofílicas , Conformação de Ácido Nucleico , Pirazóis/química , Espectrofotometria Ultravioleta , Temperatura , Termodinâmica
7.
Phys Chem Chem Phys ; 19(19): 11937-11946, 2017 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-28440391

RESUMO

The detailed photophysics of (E)-1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole (DSDP) and (E)-1,5-diphenyl-3-styryl-1H-pyrazole (DSP) has been investigated and compared to demonstrate the drastic modification of the photophysics upon dehydrogenation of the pyrazoline ring. While DSDP gives dual absorption and dual emission bands corresponding to the locally excited (LE) and the intramolecular charge transfer (ICT) species, DSP yields single absorption and emission bands for the locally excited species only. Comparative steady state and time resolved fluorometric studies reveal that aromatization of the pyrazoline ring inhibits the formation of the ICT species. Quantum chemical calculations corroborate and rationalize the inhibition of the ICT process upon aromatization through depiction of the differential electronic distributions in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the two fluorophores.

8.
Photochem Photobiol Sci ; 16(2): 159-169, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-27959373

RESUMO

The photophysics of 2,2'-pyridil has been explored thoroughly using steady state and time resolved fluorometric techniques at room temperature (RT) in liquid media as well as in glassy matrices at cryogenic temperature (77 K). Ethanol and methylcyclohexane are exploited for this purpose, as polar and non-polar media respectively. Notwithstanding the observation of multiple emissions from the fluorophore, the experiments unequivocally rule out emission from excited singlet states other than the S1 state, consistent with Kasha's rule. Among 1,2-dicarbonyl molecular systems, this behavior resembles that of α-furil, while it contradicts that of benzil and α-naphthil which exhibit S2 emissions. The dual fluorescence and dual phosphorescence of the fluorophore are ascribed to the emissions originating from the two conformers, namely near-trans and relaxed skew. Coexistence of the two conformers is substantiated by time resolved area normalized emission spectroscopy (TRANES) at both RT and 77 K. The potential energy curves (PECs) simulated from calculations based on density functional theory and its time dependent extension provide adequate support to the experimental observations.

9.
J Chem Phys ; 144(23): 234317, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27334172

RESUMO

Steady state and time resolved spectroscopic measurements have been exploited to assign the emissions from different conformations of α-furil (2, 2'-furil) in solution phase at room temperature as well as cryogen (liquid nitrogen, LN2) frozen matrices of ethanol and methylcyclohexane. Room temperature studies reveal a single fluorescence from the trans-planar conformer of the fluorophore or two fluorescence bands coming from the trans-planar and the relaxed skew forms depending on excitation at the nπ(∗) or the ππ(∗) absorption band, respectively. Together with the fluorescence bands, the LN2 studies in both the solvents unambiguously ascertain two phosphorescence emissions with lifetimes 5 ± 0.3 ms (trans-planar triplet) and 81 ± 3 ms (relaxed skew triplet). Quantum chemical calculations have been performed using density functional theory at CAM-B3LYP/6-311++G(∗∗) level to prop up the spectroscopic surveillance. The simulated potential energy curves (PECs) illustrate that α-furil is capable of giving two emissions from each of the S1 and the T1 states-one corresponding to the trans-planar and the other to the relaxed skew conformation. Contrary to the other 1,2-dicarbonyl molecular systems like benzil and α-naphthil, α-furil does not exhibit any fluorescence from its second excited singlet (S2) state. This is ascribed to the proximity of the minimum of the PEC of the S2 state and the hill-top of the PEC of the S1 state.

10.
J Fluoresc ; 26(3): 845-54, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26898642

RESUMO

Structural influence on the photophysical behavior of two pairs of molecular systems from the biologically potent benzoquinoline family, namely, dimethyl-3-(4-chlorophenyl)-3,4-dihydrobenzo[f]-quinoline-1,2-dicarboxylate, dimethyl-3-(2,6-dichlorophenyl)-3,4-dihydrobenzo[f]quinoline-1,2-dicarboxylate and their corresponding dehydrogenated analogues has been investigated exploiting experimental as well as computational techniques. The study unveils that dehydrogenation in the heterocyclic rings of the studied quinoline derivatives modifies their photophysics radically. Experimental observations imply that the photophysical behavior of the dihydro analogues is governed by the intramolecular charge transfer (ICT) process. However, the ICT process is restricted significantly by the dehydrogenation of the heterocyclic rings. Computational exertion leads to the proposition that the change in the electronic distribution in these molecular systems on dehydrogenation is the rationale behind the dramatic modification of their photophysics.

11.
Phys Chem Chem Phys ; 18(5): 3685-93, 2016 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-26758082

RESUMO

In this article, we have addressed to a demanding physicochemical aspect of therapeutic and drug research. We have reported a simple yet prospective technique that can be exploited for the controlled delivery of drugs and/or bioactive small molecules to the most relevant biomolecular target DNA. Exploiting various steady state and time resolved spectroscopic techniques together with the DNA helix melting study, we have shown that a biologically significant photosensitizer, namely, phenosafranin (PSF), can be quantitatively transferred to the DNA from the micellar nanocarrier made up of sodium tetradecyl sulfate (STS) using the external stimulant ß-cyclodextrin (ß-CD). The complexation property of ß-CD with the nanocarrier (STS) has been utilized for the controlled release of the probe from the micelle to the DNA. Non-toxicity of the stimulant and the noninvasive nature of the carrier towards the target are expected to add to the suitability of this approach from a clinical perspective.


Assuntos
DNA/química , Portadores de Fármacos/química , Nanoestruturas/química , Fenazinas/química , Fármacos Fotossensibilizantes/química , beta-Ciclodextrinas/química , Animais , Bovinos , Micelas , Estrutura Molecular , Tetradecilsulfato de Sódio/química
12.
J Photochem Photobiol B ; 154: 118-25, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26610723

RESUMO

The effect of calf-thymus DNA (ctDNA) on the lipid bound probe, formed by the cationic phenazinium dye phenosafranin (PSF) and the anionic lipid dimyristoyl-L-α-phosphatidylglycerol (DMPG), has been unearthed exploiting various spectroscopic techniques. Steady state and time-resolved fluorometric studies and measurements of circular dichroism and DNA helix melting temperature reveal that in the presence of DNA the probe is dislodged from the lipid environment and gets intercalated within the DNA helix. The work qualitatively illustrates that the anionic lipid can be used as a potential nanocarrier for delivering the cationic drugs to the most relevant biomacromolecular target, DNA.


Assuntos
DNA/química , Corantes Fluorescentes/química , Animais , Cátions/química , Bovinos , Dicroísmo Circular , Fenazinas/química , Fosfatidilgliceróis/química , Temperatura de Transição
13.
Phys Chem Chem Phys ; 17(27): 17699-709, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26082043

RESUMO

The binding interaction of a potential nervous system stimulant, 3-acetyl-4-oxo-6,7-dihydro-12H-indolo-[2,3-a]-quinolizine (AODIQ), with calf-thymus DNA (ctDNA) has been explored thoroughly. The modified photophysics of the fluorescent molecule within the microheterogeneous biomacromolecular system has been exploited to divulge the drug-DNA binding interaction. The absorption and various fluorometric measurements together with the fluorescence quenching, urea-induced denaturation study, circular dichroism and DNA-melting studies unequivocally ascertain the mode of binding of the drug with the DNA to be groove binding. Corroborating the experimental observations, molecular docking simulation projects the minor groove of the biomacromolecule to be the site of binding. Further experiments have revealed that dissociation of the drug from the drug-DNA complex can be achieved by the detergent sequestration method. Besides providing an insight into the drug-DNA interaction the work also demonstrates the surfactant-induced excretion of the drug from the biomacromolecular assembly.


Assuntos
DNA/química , Detergentes/química , Quinolizinas/química , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , DNA/metabolismo , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Concentração Osmolar , Quinolizinas/metabolismo , Espectrometria de Fluorescência , Ureia/química
14.
Artigo em Inglês | MEDLINE | ID: mdl-25698439

RESUMO

Interaction of cationic phenosafranin (PSF), anionic 8-anilino-1-naphthalene sulfonate (ANS) and non-ionic nile red (NR) have been studied with the zwitterionic phospholipid, egg yolk L-α-phosphatidylcholine (EYPC). The study reveals discernible binding interactions of the three fluorescent probes with the EYPC lipid vesicle. Once the binding of the probes with the lipid is established, the effect of cyclic oligosaccharide, ß-cyclodextrin (ß-CD), on these lipid bound probes has been investigated. Different fluorometric techniques suggest that addition of ß-CD to the probe-lipid complexes leads to the release of the probes from the lipid medium through the formation of probe-ß-CD inclusion complexes. A competitive binding of the probes between ß-cyclodextrin and the lipid is ascribed to be responsible for the effect. This provides an easy avenue for the removal of the probe molecules from the lipid environment. Extension of this work with drug molecules in cell membranes is expected to give rise to a strategy for the removal of adsorbed drugs from the cell membranes by the use of non-toxic ß-cyclodextrin.


Assuntos
Gema de Ovo/química , Corantes Fluorescentes/química , Fosfatidilcolinas/química , beta-Ciclodextrinas/química , Naftalenossulfonato de Anilina/química , Animais , Sítios de Ligação , Ligação Competitiva , Fluorometria , Oxazinas/química , Fenazinas/química
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