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A detailed computational analysis of acridine derivatives viz. acridone, 9-amino acridine hydrochloride hydrate, proflavin, acridine orange and acridine yellow is done in terms of conceptual density functional theory (CDFT). CDFT-based global descriptors-ionization potential, electron affinity, HOMO-LUMO gap, hardness, softness, electronegativity and electrophilicity index of acridine derivatives for ground state as well as excited state are estimated with the help of different hybrid functionals B3LYP/6-31G (d, p), B3LYP/6-311G (d, p), B3LYP/DGDZVP and B3LYP/LANL2DZ. Acridine derivatives show higher values of ionization potential and electron affinity in excited state as compared to ground state, indicating that these compounds are willing to accept electrons in excited state rather than donating electron. Acridone shows the maximum HOMO-LUMO energy gap in ground and excited state which implies that one-way electron transfer is most feasible with this compound. Our computed results emphasize the pronounced electron acceptor behaviour of the acridine derivatives in the excited state which has already been experimentally verified. It is observed that the trend in the computed values of the descriptors is not much improved on refinement of the basis set.

Spectroscopic analyses reveal that acridone (AD) penetrates through the structure and enters the hydrophobic cavity of the protein β-lactoglobulin (βLG). Although the protein contains two tryptophan (Trp) residues, AD interacts with only one (Trp-19), which is authenticated by the appearance of a single isoemissive point in TRANES. Alteration in the secondary structure of the protein while AD pierces through βLG is evident from the circular dichroism spectroscopic study. The ground-state interaction between AD and βLG is proven from the UV-vis spectroscopic study and the static nature of quenching of intrinsic fluorescence of the protein by the ligand. The steady-state fluorescence study in varied temperatures indicates the involvement of hydrogen bonding in the ligand-protein interaction. Further, the time-resolved fluorescence anisotropy study gives a hint of the presence of a hydrogen bond in AD-βLG interaction, which possibly involves the rotamers of Trp-19. In fact, the idea of involvement of rotamers of Trp-19 is obtained from the increase in fluorescence lifetime of βLG in the presence of AD. The docking study agrees to the involvement of hydrogen bonding in AD-βLG interaction. The direct evidence of hydrogen bonding between Trp and AD is obtained from the laser flash photolysis studies where the signature of formation of ADH• and Trp• through hydrogen abstraction between Trp and AD, loosely bound through hydrogen bonding, gets prominence. Thus, binding of AD to βLG involves hydrogen bonding in a hydrophobic pocket of the protein.

Spectroscopic and docking analyses reveal that acridone (AD) interacts with both the tryptophan (Trp) residues of bovine serum albumin (BSA) (both Trp 134 and Trp 212) in contrast to other organic ligands including other acridine derivatives which generally prefer to interact with Trp 212. The use of fluorescence spectroscopy, specifically the unusual time-resolved area normalized spectra depicting two isoemissive points with different times of evolution, confirms that AD “unusually” interacts with both the Trp residues present in the model protein. Upward curvature of the Stern Volmer plot suggests the interaction of AD with both the Trp residues present in varying microenvironments within BSA and possibly also indicates the denaturation of the protein. Ground state interaction of AD and BSA is explored using absorption spectroscopy, whereas strong perturbation in secondary and tertiary structures of the model protein on binding with the ligand is divulged from the observation of circular dichroism spectroscopy. Femtosecond fluorescence up-conversion kinetics implies that a photoinduced electron transfer reaction takes place from the Trp residue of the protein to AD, which has been authenticated using laser flash photolysis via identification of the radical ions. Binding as well as thermodynamic parameters associated with AD–BSA interaction are obtained from fluorescence studies. The prime deduction from the detailed spectroscopic and docking analyses is that AD initially interacts with Trp 212 present in the crevice of hydrophobic domain IIA of the protein and then perturbs the structure of BSA to bring about conformational changes such that it can gain access to Trp 134 housed in hydrophilic domain IB, which is possibly facilitated by hydrogen bonding.

The excitation wavelength dependent emission of carbon nano dots (CNDs) restricts their use in photophysical studies. However, instead of bare CNDs, the amine coated Ru (III) doped CNDs (Ru:CNDEDAs) are quite eligible to generate excitation wavelength independent fluorescence with high quantum yield. Herein, we report a detailed study on the photochemical interaction between two different serum albumins, bovine serum albumin (BSA) and human serum albumin (HSA), with Ru:CNDEDAs synthesized in our laboratory, using steady-state and time-resolved spectroscopic techniques. Absorption study reveals the formation of ground state complex between Ru:CNDEDAs and BSA/HSA while the circular dichroism study implies that Ru:CNDEDAs perturbs the secondary structure of the albumin proteins. Steady-state fluorescence study helps in understanding energy transfer from tryptophan, the fluorophore moiety of BSA and HSA, to Ru:CNDEDAs. Time-resolved studies within nanosecond time domain clarify the phenomenon of energy transfer from BSA/HSA to Ru:CNDEDAs with varied efficiency. Molecular dynamic simulation ascertains that the efficiency of energy transfer is highly dependent on the stability of protein-nanoparticle complex. This study provides a qualitative description regarding the structural rigidity of transport protein, BSA compared to HSA, which determines the transport ability of CNDs to deliver the desired drug molecule to the targeted cells.

A weak external magnetic field, very close to the hyperfine interactions of the system, can acts as a tool to monitor spin dynamics and assess distance between the components of the spin-correlated transient radical pair or radical ion pair (RIP). The present review focuses on the magnetic field effect (MFE) on the photo-induced electron-transfer (PET) reactions among acridine derivatives and classical as well as biological electron acceptor or donor moieties, which produce spin-correlated RIPs, in homogeneous solvents, heterogeneous micellar media and in biological nanocavities of proteins. Although a confined medium is preferred to observe prominent MFE, yet unanticipated MFE on PET between acridine derivatives [Acridone (AD) and Acridine Yellow (AY)] and classical electron donors is obtained even in homogeneous medium when it consists of impurities like water molecules. In a comparative study of interaction of another acridine derivative, Proflavin (PF+) with two electron donors which are amines of aromatic nature, MFE on PET reveal that the bulk and the structure of the electron donor govern the mechanism as well as the spin dynamics of PET. While studying interaction of PF+ with a different amine which is aliphatic in nature, MFE on PET implies that it is the nature of the solvent matrix which determines the spin dynamics of PET. The cause of discrepancy in the experimental and calculated values of B1/2 for 9-amino acridine – methyl viologen system has been delineated. Apart from micellar medium, prominent MFE on PET is also observed while studying the interaction of PF+, AY and AD with tryptophan residues present in the nanocavities of serum albumins since the inter-radical distance within primary geminate RIP is enough to make exchange interaction negligible.

Photoinduced electron transfer (PET) from a biological amine, tryptophan to a well-known acridine-derivative, proflavin has been investigated employing laser flash photolysis technique in heterogeneous AOT reverse micelles (RMs). In AOT RMs a significant magnetic field effect (MFF) on PET has been observed which authenticates the triplet spin states of the precursors of PET. The measurement of B1⁄2 value gives an indication of the extent of hyperfine interactions present in the system in AOT medium. The cause of discrepancy between calculated and experimental B1⁄2 values is explained. Further, it is observed that MFE decreases with increase in pool size of the RMs which highlights the importance of optimum separation between the corresponding radical ions pairs to maximize MFE.

In this article, we study the binding interaction of acridone (AD) with human serum albumin (HSA) using conventional spectroscopic techniques and then decipher the latent occurrence of photoinduced electron transfer (PET) using the laser flash photolysis (LFP) technique in conjunction with a weak magnetic field (MF). The experimental observations are further substantiated by docking results. An absorption study reveals the formation of a ground state complex between AD and HSA while a circular dichroism study implies that AD brings about a substantial change in the secondary and tertiary structures of the protein. A fluorescence study mainly helps in evaluation of the binding and thermodynamic parameters. This is one of the rare reports which utilize time-resolved emission spectra and time-resolved area normalized emission spectra to study drug–protein interactions. The detection of the occurrence of PET would be ignored if only the observations of conventional spectroscopic techniques had been considered. LFP detects the occurrence of PET from the tryptophan residue of HSA to AD and MF effect authenticates the triplet origin of the radical ions involved. Furthermore, the actual reaction pathway is elucidated with the help of the MF effect. Although the MF effect is generally observed in a restricted medium, in the present case the complex structure of the protein offers pseudo-confinement to the radical pairs or radical ion pairs resulting in observation of a substantial MF effect. The significance of maintaining the condition of “pseudo-confinement” or the optimum distance between radical ions originating from the acceptor and donor moieties in the observation of the MF effect has been specifically highlighted in this work by integrating the findings of the present study with our previous reports.

In this letter photoinduced interactions of methyl viologen (MV2+) with 9-aminoacridine hydrochloride hydrate (9AA-HCl) have been studied. In homogeneous medium, both photoinduced electron transfer (PET) and excited-state proton transfer (ESPT) are occurring whereas in micellar medium only PET is prevalent. Magnetic field effect confirms that the PET takes place primarily in the triplet state. Discrepancy in theoretically calculated and experimentally obtained B1/2 values indicates the presence of electron hopping mechanism. Amalgamation of this letter with our previous report indicates that 9AA-HCl may either act as an electron donor or acceptor in PET reactions under suitable condition of redox potentials.

Photoinduced interactions of 9-aminoacridine hydrochloride hydrate (9AA-HCl) with aromatic and aliphatic amines, N,N'-dimethylaniline (DMA) and triethylamine (TEA) respectively have been investigated in homogeneous water–acetonitrile (1:1) mixture as well as in heterogeneous cetyltrimethyl ammonium bromide (CTAB) micellar media using UV–vis absorption, steady-state as well as time-resolved fluorescence spectroscopies and laser flash photolysis technique associated with a weak external magnetic field (MF). Differential modes of fluorescence quenching of 9AA-HCl with DMA and TEA corroborated with absorption studies reveal their disparity in the mechanism of interactions. Excited state proton transfer (ESPT) and photoinduced electron transfer (PET) are the phenomenon that have been found to be involved in with DMA, whereas with TEA ground-state complex formation, ground-state proton transfer and PET are prevalent. Discrepancy in pH of the interfacial and hydrophobic regions of CTAB facilitates the partitioning of the protonated and neutral forms of 9AA-HCl leading to differential occupational sites of the acceptor and donor moieties in the micellar medium, thus making the study more intriguing. Another important aspect of the present study is the use of MF to confirm the occurrence of PET, authenticate the spin-state of the intermediates thus formed and also to resolve the process of PET and ESPT.

We aim to find out the extent of stability of the excimer of 9-aminoacridine hydrochloride hydrate (9AA), a prospective PDT drug, in different confined media with varying cavity size. When confined in cetyltrimethyl ammonium bromide micelles, although at low concentration of 9AA, only a single distinct peak (λ(max) at 460 nm) with a shoulder at 485 nm is observed in steady-state fluorescence spectrum, yet with increase in concentration the peak and the shoulder merge with simultaneous emergence of another peak at 535 nm, which is assigned to excimer. Similar behavior is also observed in Triton-X, crown ether, α-cyclodextrin, β-cyclodextrin, and homogeneous aqueous medium. The formation of excimer, which reflects the extent of confinement of 9AA, is maximum in β-cyclodextrin followed by others. Steady-state and time-resolved fluorescence studies along with TRES and TRANES analyses coupled with anisotropy data and transient absorption studies reveal the presence of monomer-dimer equilibrium of 9AA in the excited state. Molecular modeling indicates that the structure of excimer is stabilized by locking of the two monomeric species via four hydrogen bonds formed between the amino-H and imino-N of 9AA monomers, whereas the dimer in the ground state has only two such hydrogen bonds.

The effect of low magnetic field (MF) of the order of 0.01–0.08 T on the reactions involving spin-correlated radical ion pairs generated through electron transfer as intermediates is an interplay between diffusion dynamics and spin dynamics of the individual radical ions in the solvent cage. In this paper, we have made an attempt to study photoinduced electron transfer reactions between three aromatic amines and acridone in ethanol medium using a weak external MF. Although the MF effect is conventionally observed appreciably in heterogeneous organized medium, in the present case a considerable MF effect is obtained in homogeneous medium, i.e., ethanol. The occurrence of this rare phenomenon has been attributed to the presence of water molecules as impurities in ethanol.

The study of binding of small molecules with supramolecular architecture comprises of one of the thriving areas of research today. In the present study, spectroscopic techniques have been used to decipher the interaction of Acridine Yellow with Cucurbit[7]uril and explore the consequence of host–guest interaction on the photophysical properties of the dye. Moreover, isothermal titration calorimetry has been used to unravel the thermodynamics of interaction. The probable causes of incongruity of the results obtained from spectroscopy and calorimetry have been rationalized. 1 H NMR study and geometry optimization of the guest molecule confirm the actual mode of host–guest interaction.

Conventional spectroscopic tools such as absorption, fluorescence, and circular dichroism spectroscopy used in the study of photoinduced drug-protein interactions can yield useful information about ground-state and excited-state phenomena. However, photoinduced electron transfer (PET) may be a possible phenomenon in the drug-protein interaction, which may go unnoticed if only conventional spectroscopic observations are taken into account. Laser flash photolysis coupled with an external magnetic field can be utilized to confirm the occurrence of PET and authenticate the spin states of the radicals/radical ions formed. In the study of interaction of the model protein human serum albumin (HSA) with acridine derivatives, acridine yellow (AY) and proflavin (PF(+)), conventional spectroscopic tools along with docking study have been used to decipher the binding mechanism, and laser flash photolysis technique with an associated magnetic field (MF) has been used to explore PET. The results of fluorescence study indicate that fluorescence resonance energy transfer takes place from the protein to the acridine-based drugs. Docking study unveils the crucial role of Ser 232 residue of HSA in explaining the differential behavior of the two drugs towards the model protein. Laser flash photolysis experiments help to identify the radicals/radical ions formed in the due course of PET (PF(•), AY(•-), TrpH(•+), Trp(•)), and the application of an external MF has been used to characterize their initial spin-state. Owing to its distance dependence, MF effect gives an idea about the proximity of the radicals/radical ions during interaction in the system and also helps to elucidate the reaction mechanisms. A prominent MF effect is observed in homogeneous buffer medium owing to the pseudoconfinement of the radicals/radical ions provided by the complex structure of the protein.

Interaction of acridine yellow (AY) with three amines, viz., dimethylaniline (DMA), 4,4′-bis(dimethylamino)diphenylmethane (DMDPM) and triethylamine (TEA) in homogeneous medium is explored. DMA and DMDPM participate only in photoinduced electron transfer (PET) with AY whereas TEA is found to be involved in both PET and charge-transfer complex formation. The novelty of the present work lies in the fact that all the three AY-amine systems exhibit magnetic field effect on PET reactions in homogeneous medium due to inter-radical hydrogen bond mediated by intervening water molecules, which sustain the geminate characteristics as well as the spin correlation of radical ion pairs, that are formed as primary intermediates through PET.

Photoinduced electron transfer (PET) between proflavin (PF + ) and two aromatic amines viz., dimethylaniline (DMA) and 4,4′-bis(dimethylamino)diphenylmethane (DMDPM) is studied in homogeneous and heterogeneous media using steady-state as well as time-resolved fluorescence spectroscopy and laser flash photolysis with an associated magnetic field. Ionic micelles have been used to study the effect of charge of proflavin on PET with amines. Magnetic field effect on PET reactions reveals that the parent spin-state of precursors of PET for DMA-PF + system is singlet while for DMDPM-PF + system is triplet, implying that the dynamics of PET is influenced by the structure of the donor.

Interaction of triethylamine (TEA) with cationic proflavin (PF+) in homogeneous and micellar media is studied using absorption spectroscopy, steady-state as well as time-resolved fluorescence spectroscopy and laser flash photolysis in conjunction with an external magnetic field. The two prime phenomena that have been highlighted in this study are photoinduced electron transfer (PET) and ground-state complex formation. This study shows that it is the medium which determines the reaction pathways to be followed. Magnetic field effect (MFE) helps to elucidate the reaction mechanism involved and this work also highlights the distance dependence factor associated with MFE.

The interaction of bovine serum albumin (BSA) with proflavin was investigated by spectroscopic tools like absorption and fluorescence spectroscopy as well as laser flash photolysis. Absorption spectroscopy proved the formation of ground-state BSA–proflavin complex. Proflavin was found to quench the intrinsic fluorescence of BSA via static quenching. High value of quenching constant suggested that energy transfer occurred from BSA to proflavin. Distance between the fluorophore in the protein and the ligand (proflavin) was evaluated. Binding constant and number of binding site were determined for proflavin–BSA interaction both in phosphate buffer (pH∼6.8) and in sodium dodecylsulphate media. The values of the thermodynamic parameters suggested that the key interacting forces are van der Waal's interaction and hydrogen bonding. Laser flash photolysis study reconfirmed the formation of complex between BSA and proflavin.