Design, synthesis, and stability of (1-amino-4-(3-bromopropoxy) anthracene-9,10-dione)pentacarbonylrhenium(I) triflate: first X-ray crystallographic structure of a Re(CO)5(N-donor)

In a bid to functionalise doxorubicin with rhenium carbonyl, we designed and synthesized two doxoru-bicin analogues, 1-(3-trimethylammoniumpropoxy)-4-hydroxyanthraquinone triflate (A(1)) and 1-amino-4-(3-trimethylammoniumpropoxy) anthraquinone triflate (A(2)), via a simple 3-step procedure, and obtained X-ray crystal structures for them. Reaction of A1 with Re(CO)(5)(OTf) afforded complex 1 in 40% yield. Based on a combination of ultraviolet/visible, proton nuclear magnetic resonance spectroscopies, density functional theory calculations, and, in particular, infrared spectroscopy and electrospray ionization mass spectrometry, complex 1 was deduced to be [{fac-Re(CO)(3)(2-deproto-A1)}(2)(mu(2)-OTf)]OTf, in which A(1) co-ordinates to Re in a bidentate fashion and a triflate anion bridges two Re(CO)(3) moieties. Reaction of A(2) with various rhenium carbonyl synthons was intractable, but 1-amino-4-(3-bromopropoxy)anthraquinone (A2-a), a precursor of A(2) , reacted with Re(CO)5(OTf) to yield complex 2 in 65% yield. A single crystal X-ray crystallographic study established complex 2 to be [Re(CO)(5)(A2-a)]OTf, in which the-NH2 of A2-a coordinates to Re in a monodentate fashion. Complex 2 crystallized in the P2 1 /n monoclinic space group and packs by vertically stacking on top of each other and with a horizontal displacement of 49 degrees from the neighbouring pairs of molecules. This is similar to the crystal packing of A1 , but not A(2) . We observed that complexes 1 and 2 are unstable in solution, and dissociated in dimethylsulfoxide with first order rate constants of 0.029 +/- 0.001 h(-1) and 18 +/- 2 h(-1) respectively; in water, complex 1 dissociated almost immediately. Molecular orbital analysis indicated that the low bonding interaction between the coordi-nating atoms and Re for complex 1 and high energy of the bonding molecular orbital for complex 2 are likely to be the basis of weak coordination of the anthraquinones to rhenium carbonyl. Thus, with regard to the intended objective to modulate the pharmacological profile of doxorubicin, direct coordination of rhenium carbonyl is certainly not feasible.(c) 2023 Elsevier B.V. All rights reserved.

Automated summary

In this study, two doxorubicin analogues (A(1) and A(2)) were designed and synthesized, and their X-ray crystal structures were obtained. It was found that A(1) reacted with Re(CO)(5)(OTf) to form complex 1, and A(2) reacted with Re(CO)5(OTf) to form complex 2. Both complexes were found to be unstable in solution and showed weak coordination to rhenium carbonyl. Therefore, direct coordination of rhenium carbonyl is not feasible for modulating the pharmacological profile of doxorubicin.