Exploring the Utility of Tandem Thermal–Photochemical CO Delivery with CORM‑2

Among the most popular and widely
studied CO-releasing molecules
(CO-RMs) for biological research is Ru2Cl4(CO)6 (CORM-2). When dissolved in DMSO (the solubilizing agent
used in preclinical trials), the dimer cleaves into monomeric DMSO-ligated
Ru subunits; the rate of this reaction and behavior of the products
formed are thus highly relevant to the efficacy of CORM-2 in vivo. FT-IR spectroscopy was used to monitor this reaction
in DMSO and also to monitor the reactivity of CORM-2 and of the monomeric
DMSO-ligated derivatives in mouse serum. While the CORM-2 dimer readily
liberates CO in mouse serum under ambient conditions, the monomeric
Ru subunits formed in DMSO solution do not. This demonstrates that
a substantial fraction of the CO-delivery agent being introduced via
DMSO solutions would appear to be, in fact, inactive. Photochemical
irradiation readily liberates CO from the inactive species, and thus
a combined thermal–photochemical approach can greatly improve
the yield of CO delivery. Ultrafast experiments indicate that CO loss
from the DMSO-ligated monomers is a primary photochemical process.
Viewing these results for the popular CORM-2 as a series of proof-of-principle
observations, these results demonstrate that predissolution of a CO-RM
in any solvent may generate products that are no longer physiologically
active, and thus the time between dissolution and injection should
always be carefully monitored;
this has been seldom reported or considered in CO-RM studies to date.
Although a combined thermal–photochemical CO-release approach
has not been taken previously, we demonstrate that such an approach
is practically quite useful for one of the most popular CO-RMs currently
being studied, and thus it is clear that such an approach will be
needed to achieve the full potential of many current and future CO-RMs.