Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme‐Triggered CO‐Releasing Molecules (ET‐CORMs)

Romanski, Steffen; Kraus, Birgit; Schatzschneider, Ulrich; Neudörfl, Jörg‐Martin; Amslinger, Sabine; Schmalz, Hans‐Günther

doi:10.1002/anie.201006598

Cited by 176 publications

(152 citation statements)

References 33 publications

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“…Enzyme-triggered CORMs (ET-CORMs) make use of the presence of esterases in cells to bring about CO release at metal centres. [21][22][23][24] Triggering using small molecules is also possible, with the combination of a CORM with a second chemical agent [25][26][27] allowing temporal control of release. More exotic approaches have also been explored, for example release triggered by electromagnetic heating.…”

Section: Introductionmentioning

confidence: 99%

PhotoCORMs: CO release moves into the visible

Wright

2016

Dalton Trans.

117

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The potential of carbon monoxide to act as a therapeutic agent is now well-established. Controlled delivery of CO is best achieved using 'CORMs': molecules which release known amounts of carbon monoxide in response to a stimulus. Metal carbonyl complexes will release CO if irradiated with ultraviolet light, but it is only in the past five years that development of true 'photoCORMs' has been explored. Recent exciting developments in this area now show that design of photoCORMs operating well into the visible region is achievable. In this Perspective, we examine the growth of photoCORMs from their origins in the photophysics of metal carbonyls to the latest visible-light agents.

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Section: Introductionmentioning

confidence: 99%

PhotoCORMs: CO release moves into the visible

Wright

2016

Dalton Trans.

117

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“…To date the majority of CORMs are transition metal (TM) carbonyl complexes which under different stimuli are able to deliver CO to diseased or inflamed tissues in order to initiate and promote therapeutic effects at the site of disease. CO release in these molecules may be triggered by different strategies which include simple CO dissociation [4][5][6] , redox or ligand exchange mediated processes [7][8][9][10][11][12] , enzymatic triggering 13,14 or the use of electromagnetic radiation. [15][16][17] In general, at present, CORMs are not designed to target a specific receptor or intracellular target and their potential utility is credited to their fundamental ability to liberate CO.…”

Section: Introductionmentioning

confidence: 99%

Live-Fibroblast IR Imaging of a Cytoprotective PhotoCORM Activated with Visible Light

et al. 2013

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Carbon monoxide releasing molecules (CORMs) are an emerging class of pharmaceutical compounds currently evaluated in several preclinical disease models. There is general consensus that the therapeutic effects elicited by the molecules may be directly ascribed to the biological function of the released CO. It remains unclear, however, if cellular internalization of CORMs is a critical event in their therapeutic action. To address the problem of cellular delivery, we have devised a general strategy which entails conjugation of a CO-releasing molecule (here a photoactivated CORM) to the 5'-OH ribose group of vitamin B12. Cyanocobalamin (B12) functions as the biocompatible water-soluble scaffold which actively transports the CORM against a concentration gradient into the cells. The uptake and cellular distribution of this B12-photoCORM conjugate is demonstrated via synchrotron FTIR spectromicroscopy measurements on living cells. Intracellular photoinduced CO release prevents fibroblasts from dying under conditions of hypoxia and metabolic depletion, conditions that may occur in vivo during insufficient blood supply to oxygen-sensitive tissues such as the heart or brain.

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“…17 Regioselective deprotonation of 23 under either kinetic (LDA, THF) or thermodynamic (LiHMDS, TPPA) 14 control, subsequent O-acetylation and final complexation led to rac-12 and rac-13, respectively, as pure isomers after chromatography (Scheme 4).…”

Section: Synthesismentioning

confidence: 99%

“…13 As a novel concept, we recently introduced acyloxybutadieneFe(CO) 3 complexes of type 3 as enzyme-triggered CO-releasing molecules (ET-CORMs). 14 The earlier observation, that enol complexes of type 4 are labile and decompose under oxidative conditions, suggested their suitability as CORMs (Scheme 1). As stable (and "storable") precursors we devised the corresponding esters, i.e.…”

Section: Introductionmentioning

confidence: 99%

Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure–activity relationship study

et al. 2012

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A series of η 4 -acyloxycyclohexadiene-Fe(CO) 3 complexes was prepared and fully characterized by spectroscopic methods including single crystal X-ray diffraction. For this purpose a new synthetic access to differently acylated 1,3-and 1,5-dienol-Fe(CO) 3 complexes was developed. The enzymatically triggered CO release from these compounds was monitored (detection of CO through GC and/or by means of a myoglobin assay) and the anti-inflammatory effect of the compounds was assessed by a cellular assay based on the inhibition of NO-production by inducible NO synthase (iNOS). It was demonstrated that the properties (rate of esterase-triggered CO release, iNOS inhibition, cytotoxicity) of the complexes strongly depend on the substitution pattern of the π-ligand and the nature of the acyloxy substituent.

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Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme‐Triggered CO‐Releasing Molecules (ET‐CORMs)

Cited by 176 publications

References 33 publications

PhotoCORMs: CO release moves into the visible

PhotoCORMs: CO release moves into the visible

Live-Fibroblast IR Imaging of a Cytoprotective PhotoCORM Activated with Visible Light

Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure–activity relationship study

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