Detection of Hypoxanthine from Inosine and Unusual Hydrolysis of Immunosuppressive Drug Azathioprine through the Formation of a Diruthenium(III) System

Abstract

Hypoxanthine (hpx) is an important molecule for both biochemistry research and biomedical applications. It is involved in several biological processes associated to energy and purine metabolism and has been proposed as a biomarker for a variety of disease states. Consequently, the discovery and development of systems suitable for the detection of hypoxanthine is pretty appealing in this research field. Thus, we have obtained a stable diruthenium (III) compound in its dehydrated and hydrated forms with formula [{Ru(µ-Cl)(µ-hpx)}2Cl4] (1a) and [{Ru(µ-Cl)(µ-hpx)}2Cl4]·2H2O (1b), respectively. This purine-based diruthenium(III) system was prepared from two very different starting materials, namely, inosine and azathioprine, the latter being an immunosuppressive drug. Remarkably, it was observed that an unusual azathioprine hydrolysis occurs in the presence of ruthenium, thus generating hypoxanthine instead of the expected 6-mercaptopurine antimetabolite, so that the hpx molecule is linked to two ruthenium(III) ions. 1a and 1b were characterized through IR, SEM, powder and single-crystal X-ray Diffraction and Cyclic Voltammetry (CV). The electrochemical studies allowed us to detect the hpx molecule when coordinated to ruthenium in the reported compound. The grade of sensitivity, repeatability and stability reached by this diruthenium system make it potentially useful and could provide a first step to develop new sensor devices suitable to detect hypoxanthine.

A Gadolinium(III) Complex Based on the Thymine Nucleobase with Properties Suitable for Magnetic Resonance Imaging

“…As a continuation of our interest in investigating biomolecule-based complexes [ 15 , 16 , 17 , 18 , 19 , 20 ], herein we report the synthesis and characterization of a new gadolinium(III) complex of formula [Gd(thy) 2 (H 2 O) 6 ](ClO 4 ) 3 ·2H 2 O ( 1 ) [thy = thymine], which exhibits a linearly disposed thymine-Gd III -thymine structure ( Figure 1 and Figure S1 ). 1 displays the first reported crystal structure based on gadolinium and thymine and is a suitable candidate for contrast-enhanced magnetic resonance (MR) imaging applications.…”

Rational Assembly of Polymer–Metal Coordination Hierarchical Superstructures for Azathioprine-Responsive Electrodes in Biological Samples

“…These diluted serum samples are transferred to an electrochemical cell containing 10 mL of PBS. Then, known concentrations of AP (5,10,15, and 20 M) were spiked into the electrochemical cell. The recovery results for all of the reduction peak currents determined by DPV (Figure 8A) are summarized in Table 2.…”

“…Currently, the increase in azathioprine (AP; IUPAC 6-[(1-methyl-4-nitro-1 H -imidazol-5-yl)­thio]-9 H -purine) and its detection study are seen as very vital research prospects from the perspective of scientific, chemical, and biological development. − AP is a purine synthesis inhibitor that is also used as an immunosuppressive drug along with other medicines to deter organ transplantation rejection . AP is also utilized to treat autoimmune diseases like rheumatoid arthritis . AP is a precursor of a drug that is transformed in the human body into its mercaptopurine and acts by reducing the impact of certain cells in the body’s immune system .…”

“…4 AP is also utilized to treat autoimmune diseases like rheumatoid arthritis. 5 AP is a precursor of a drug that is transformed in the human body into its mercaptopurine and acts by reducing the impact of certain cells in the body's immune system. 6 The National Eczema Society of the United Kingdom lists AP as a potent antidote for skin ailments.…”

Efficient and Practical Radiosynthesis of Novel [131I]-Xanthine and [131I]-Hypoxanthine

“…Together with xanthine, hypoxanthine may provide a sensitive indicator for physiological diseases, and therefore has been proposed as a biomarker for a diverse range of disease states, including Alzheimer's disease, multiple sclerosis, and colorectal cancer [4]. It is also found that local secretion of hypoxanthine by human adipose tissues was increased under hypoxia [5].…”