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Background: Drug-protein complexes is one of the crucial factors when analyzing the pharmacokinetics and pharmacodynamics of a drug because they can affect the excretion, distribution, metabolism and interaction with target tissues. Objectives: The aim of this study was to investigate the interaction of human hemoglobin (Hb) and angiotensin I converting enzyme inhibitory peptide (ACEIP) in the absence and presence of different-frequency electromagnetic fields (EMF). Methods: Various spectroscopic methods like fluorescence spectroscopy, ultraviolet, circular dichroism and conductometry techniques were applied to investigate Hb-ACEIP interaction in the absence and presence of EMF. Result: The presented spectroscopic studies indicated that EMF changed the interaction between Hb and ACEIP. The a-helix content of Hb decreased upon binding to ACEIP and conductivity of the solution enhanced upon binding. Based on Stern-Volmer equations, it could be stated that the Hb-ACEIP affinity was higher in the presence of EMF. Conclusion: It can be concluded that for patients who use the drug to control blood pressure, a low-frequency electromagnetic field would have a positive effect on the uptake of the drug.

For the first time, the binding of ropinirole hydrochloride (ROP) and aspirin (ASA) to human holo-transferrin (hTf) has been investigated by spectroscopic approaches (fluorescence quenching, synchronous fluorescence, time-resolved fluorescence, three-dimensional fluorescence, UV-vis absorption, circular dichroism, resonance light scattering), as well as zeta potential and molecular modeling techniques, under simulated physiological conditions. Fluorescence analysis was used to estimate the effect of the ROP and ASA drugs on the fluorescence of hTf as well as to define the binding and quenching properties of binary and ternary complexes. The synchronized fluorescence and three-dimensional fluorescence spectra demonstrated some micro-environmental and conformational changes around the Trp and Tyr residues with a faint red shift. Thermodynamic analysis displayed the van der Waals forces and hydrogen bonds interactions are the major acting forces in stabilizing the complexes. Steady-state and time-resolved fluorescence data revealed that the fluorescence quenching of complexes are static mechanism. The effect of the drugs aggregating on the hTf resulted in an enhancement of the resonance light scattering (RLS) intensity. The average binding OPEN ACCESSMolecules 2012, 17 3115 distance between were computed according to the forster non-radiation energy transfer theory. The circular dichroism (CD) spectral examinations indicated that the binding of the drugs induced a conformational change of hTf. Measurements of the zeta potential indicated that the combination of electrostatic and hydrophobic interactions between ROP, ASA and hTf formed micelle-like clusters. The molecular modeling confirmed the experimental results. This study is expected to provide important insight into the interaction of hTf with ROP and ASA to use in various toxicological and therapeutic processes.

The interaction between cyclophosphamide hydrochloride (CYC) and aspirin (ASA) with human serum albumin (HSA) was studied by various kind of spectroscopic, ζ potential and molecular modeling under physiological conditions. The fluorescence data showed that the binding of drugs to proteins caused strong static fluorescence quenching. The analysis of the fluorescence quenching of HSA in the binary and ternary systems displayed that ASA was affected by the complex formed between CYC and HSA. Moreover, CYC was influenced by the HSA-ASA complex. The inherent binding information, including the quenching mechanism, binding constants, number of binding sites, effective quenching constant, fraction of the initial fluorescence and thermodynamic parameters were measured by the fluorescence quenching technique at various temperatures. In addition, according to the synchronous fluorescence spectra of HSA, the results showed that the fluorescence quenching of HSA originated from the Trp and Tyr residues, and indicated a conformational change of HSA with the addition of the drugs. Far-UV CD spectra of HSA were recorded before and after the addition of ASA and CYC as binary and ternary systems. An increase in intensity of the positive CD peak of HSA was observed in the presence of the drugs. The results were interpreted by excited interactions between the aromatic residues of the HSA binding sites and the drugs bound to them. The distance r between donor and acceptor was obtained by the Forster energy according to fluorescence resonance energy transfer (FRET) and found to be 2.35 nm and 1.78 nm for CYC and ASA, respectively. This confirmed the existence of static quenching for proteins in the presence of CYC and ASA. Furthermore, docking studies pointed at a reduction of the affinity of each of the drug compounds to the protein in the presence of the other in meaningful amounts. Pre-binding of any of the said compounds forced the second to bind in a non-optimized location and orientation. The potential at the electrokinetic shear surface of the protein-drug solution were measured at several concentrations of the drugs by the ζ potential technique, which confirmed experimental and theoretical results.