Unveiling Luminescent Ir^I and Rh^I N‐Heterocyclic Carbene Complexes: Structure, Photophysical Specifics, and Cellular Localization in the Endoplasmic Reticulum

Abstract

Complexes of RhI and IrI of the [M(COD)(NHC)X] type (where M=Rh or Ir, COD=1,5‐cyclooctadiene, NHC=N‐heterocyclic carbene, and X=halide) have recently shown promising cytotoxic activities against several cancer cell lines. Initial mechanism of action studies provided some knowledge about their interaction with DNA and proteins. However, information about their cellular localization remains scarce owing to luminescence quenching within this complex type. Herein, the synthesis of two rare examples of luminescent RhI and IrI [M(COD)(NHC)I] complexes with 1,8‐naphthalimide‐based emitting ligands is reported. All new complexes are comprehensively characterized, including with single‐crystal X‐ray structures. Steric crowding in one derivative leads to two distinct rotamers in solution, which apparently can be distinguished both by pronounced NMR shifts and by their respective spectral and temporal emission signatures. When the photophysical properties of these new complexes are exploited for cellular imaging in HT‐29 and PT‐45 cancer cell lines, it is demonstrated that the complexes accumulate predominantly in the endoplasmic reticulum, which is an entirely new finding and provides the first insight into the cellular localization of such IrI(NHC) complexes.

Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase

“…The design of drug candidates based on metal NHC complexes has been dominated by gold and silver as metals, however, more recently, an increasing number of metals has demonstrated very promising results, including, for example, rhodium [ 8 , 9 , 10 , 11 , 12 ] and iridium [ 12 , 13 ] species.…”

Bis-N-Heterocyclic Carbene Complexes of Coinage Metals Containing Four Naphthalimide Units: A Structure–Emission Properties Relationship Study

“…In comparison with the precursor 2a , compounds 3 – 5 displayed a mixture of strong excimeric and very weak monomeric emission bands in solution and pure excimeric emission bands in the solid state (Figure and Figures S36 and S37). However, although in the emission spectrum of precursor 2c (Figure and Figure S36), a mixture of excimeric and internal charge transfer (ICT) emission bands appeared, the amine derivative compound 6 only showed an intense excimeric emission band at λ max = 490 nm, where its position is invariant with the solvent polarity (in non-hydrogen-bonding solvents) (Figure S38). The formation of an intramolecular hydrogen bond in the excited state S 1 (Figure S39) and the calculated difference density map of the same state further confirmed the nature of the excimeric emission for compound 6 (Figure S40).…”

“…The synthesis of new luminescent compounds has always been a fascinating topic of research. Many chemists and biochemists have made attempts to develop new fluorophores for use in various research fields. , Recently, aromatic π-systems such as perylene and naphthalene mono- or bis-imide derivatives have attracted more attention due to their interesting photophysical properties − and applications in biochemistry, − materials chemistry, − and sensing. − The photophysical properties of these compounds can be controlled by tuning (1) the substituents on the aromatic rings and (2) the aggregation and π-stacking of the aromatic rings in the solid state (either in the self-assembled materials or in the discrete molecular species). , For example, the presence of electron donor groups on the aromatic ring of N-substituted naphthalimides (NNIs) creates a charge transfer (CT) state that lies between the singlet and triplet ππ* excited states and causes an efficient phosphorescence from the 3 ππ* state . It has been well established that the aggregation of aromatic rings usually causes a quenching (ACQ) in the luminescence signals of the perylene mono- or bis-imides .…”

Luminescent Complexes of Platinum, Iridium, and Coinage Metals Containing N-Heterocyclic Carbene Ligands: Design, Structural Diversity, and Photophysical Properties

“…Naphthalimide (NI) is a versatile organic chromophore and has been widely used in fluorescent molecular probes and as DNA targeting, anticancer, and cellular imaging agents. ,,, More recently, efforts were devoted to prepare metal complexes containing this organic chromophore. − …”