Naphthalene Triplet Excited State as a Probe for the Assessment of Drug Distribution in Binary Protein Systems

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• 作者：Rau虂l Pe虂rez-Ruiz ; Rafael Alonso ; Edurne Nuin ; Inmaculada Andreu ; M^a Consuelo Jime虂nez ; Miguel A. Miranda
• 刊名：Journal of Physical Chemistry B
• 出版年：2011
• 出版时间：April 21, 2011
• 年：2011
• 卷：115
• 期：15
• 页码：4460-4468
• 全文大小：1272K
• 年卷期：v.115,no.15(April 21, 2011)
• ISSN：1520-5207

文摘

Three drugs containing the naphthalene (NP) chromophore, namely, naproxen (NPX), propranolol (PPN), and cinacalcet (CIN), but with different affinities toward serum albumins (SAs) and 伪-1-acid glycoproteins (AAGs) have been employed for the assessment of drug distribution in binary SA/AAG systems. These three drugs represent an appropriate choice for checking whether a methodology based on transient absorption spectroscopy of a given reporter can be employed for discrimination between different distribution patterns in multicompartmental biological media. Thus, upon laser flash photolysis (LFP) of NPX, PPN, and CIN in the presence or absence of proteins, the NP triplet excited state (³NP*) at 420 nm was always detected, although the kinetics of the decay traces was structure- and medium-dependent. In aerated PBS, only a very short triplet lifetime (蟿_T) was found (1鈭? 渭s). By contrast, in the presence of SAs, two longer triplet lifetimes (5鈭?6 渭s) were observed, ascribed to ³NP* within site I and site II. Upon binding to AAGs, only a long 蟿_T (15鈭?7 渭s) was found. When the two proteins were present simultaneously in the same media, fitting of the decay traces was clearly consistent with a distribution of the drug between the different biological compartments and the bulk solution, which correlates well with the known protein affinities of every drug. Experiments were performed in both human (HSA/HAAG) and bovine protein media (BSA/BAAG). The results showed that SAs are the major carriers for NPX; by contrast, PPN binds preferentially to AAGs. An intermediate situation was found for CIN, which presents comparable affinity for both proteins. The results obtained for the two enantiomers of each drug were very similar, although a small stereodifferentiation was observed between the triplet lifetimes in the protein binding sites.