Organic Photo-responsive Carbon Monoxide Molecules and Their Therapeutic Applications(Invited)
Building upon the groundbreaking discovery and colleagues regarding the unique signaling role of nitric oxide(NO)in the cardiovascular system—a finding that earned them the Nobel Prize in Medicine—the therapeutic utility of gasotransmitter molecules,particularly carbon monoxide(CO)and hydrogen sulfide(H2S),has garnered considerable interest within the scientific community.While historically CO has been recognized for its toxicity,due to its ability to bind with hemoglobin forming carboxyhemoglobin(COHb)and thereby obstruct oxygen transport to tissues and organs,leading potentially to hypoxia or fatal consequences,recent studies have illuminated its critical role as a signaling molecule.This research has highlighted CO's capacity to modulate cellular behaviors and offer therapeutic advantages when administered in precise,controlled concentrations.Notably,CO has demonstrated efficacy in promoting vasodilation,reducing inflammation,combating cancer,and inhibiting apoptosis.However,the clinical application of CO as a therapeutic agent faces significant hurdles due to its brief physiological half-life,restricted transportability,and the challenges associated with maintaining therapeutic concentrations within the physiological range.Recent advancements have led to the development of carbon monoxide-releasing molecules(CORMs),which provide a controlled and efficient delivery of CO,surpassing the stability issues of direct inhalation and minimizing biosafety risks.The versatility of CORMs supports targeted delivery via chemical modifications and encapsulation in drug carriers,enabling diverse therapeutic uses.Traditional CORMs,often metal carbonyl compounds,consist of a central metal ion bonded to ligands,typically organic molecules,facilitating CO release through coordinated mechanisms.Notably,iron pentacarbonyl(Fe(CO)5)exemplifies such CORMs,releasing CO via ligand exchange.This innovation in CORM design,including the adjustment of ligands and coordination strategies,signifies a pivotal advancement in exploiting CO's therapeutic benefits.To achieve more precise control over the release concentration of carbon monoxide(CO)at pathological sites and to address the challenges associated with poor spatial accuracy of delivery and unclear release mechanisms,researchers have turned their attention to designing carbon monoxide-releasing molecules(CORMs)sensitive to stimuli such as light,sound,magnetism,and heat.This innovative approach not only deepens our understanding of CORMs from a multidimensional perspective but also expands their potential applications.Consequently,an increasing focus has been placed on the development of photo-responsive carbon monoxide donor molecules(Photo-CORMs).Photo-CORMs,which release CO under specific wavelengths of laser light,leverage the advantages of efficiency,safety,and controllability.This light-responsive CO release mechanism endows Photo-CORMs with substantial potential for applications in biomedicine and beyond.Current research on Photo-CORMs predominantly revolves around metal carbonyl complexes.Despite the many benefits of traditional metal carbonyl Photo-CORMs,their major limitation lies in the rapid exchange of ligands under physiological conditions,leading to premature CO release and,consequently,suboptimal therapeutic outcomes.Moreover,traditional metal-centered Photo-CORMs present challenges such as high costs,poor stability,selective deficiency,and intrinsic toxicity.Addressing the drawbacks of traditional metal-centered Photo-CORMs,the scientific community is increasingly exploring organic Photo-CORMs,such as cyclic aromatic α-diketones,fluorescein analogs,flavonols,and 3-hydroxybenzo-[g]quinolones.These organic variants offer enhanced biocompatibility and can be activated across a broad light spectrum,from ultraviolet to near-infrared,for CO release.Their adaptable structural design permits modifications to tailor properties and reactivity,enabling the precise engineering of CO release mechanisms for targeted biomedical applications.Previous reviews have summarized traditional CORMs and Photo-CORMs.As a supplement to these reviews,this paper focuses on recent research on organic Photo-CORMs,providing a concise introduction to their classification,photophysical properties,and discusses their modes of administration and roles in disease treatment.Ultimately,this review offers insights into the future development of organic Photo-CORMs,guiding the design and development of more effective therapeutic strategies.This endeavor not only underscores the importance of continued innovation in the field of gasotransmitter research but also highlights the potential of organic Photo-CORMs to revolutionize therapeutic approaches through precise,controlled release of CO.
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