Calcium phosphate has excellent biocompatibility due to its chemical similarity to human hard tissue (bone and teeth). In nanoparticulate dispersed form, it can be used as a carrier in biological systems, e.g. to transfer nucleic acids or drugs. If such nanoparticles are suitably functionalized with fluorescing dyes, they can also be used for imaging or for photodynamic therapy.

A new rhenium tricarbonyl complex of a bis(quinoline)-derived ligand (2-azido-N,N-bis((quinolin-2-yl)methyl)ethanamine, L–N₃), namely [Re(CO)₃(L–N₃)]Br was synthesized and characterized in-depth, including by X-ray crystallography. [Re(CO)₃(L–N₃)]Br exhibits a strong UV absorbance in the range 300–400 nm with a maximum at 322 nm, and upon photoexcitation, shows two distinct emission bands at about 430 and 560 nm in various solvents (water, ethylene glycol). [Re(CO)₃(L–N₃)]Br could be conjugated, on a solid phase, to a peptide nucleic acid (PNA) oligomer using the copper(I)-catalyzed azide–alkyne cycloaddition reaction (Cu–AAC, “click” chemistry) and an alkyne-containing PNA building block to give Re–PNA. It was demonstrated that upon hybridisation with a complementary DNA strand (DNA), the position of the maxima and emission intensity for the hybrid Re–PNA·DNA remained mainly unchanged compared to those of the single strand Re–PNA. The rhenium-containing PNA oligomer Re–PNA could be then mediated in living cells where they have been shown to be non-toxic contrary to the general notion that organometallic compounds are usually unstable under physiological conditions and/or cytotoxic. Furthermore, Re–PNA could be detected in living cells using fluorescent microscopy.

Rheb is a homolog of Ras GTPase that regulates cell growth, proliferation, and regeneration via mammalian target of rapamycin (mTOR). Because of the well established potential of activated Ras to promote survival, we sought to investigate the ability of Rheb signaling to phenocopy Ras. We found that overexpression of lipid-anchored Rheb enhanced the apoptotic effects induced by UV light, TNFα, or tunicamycin in an mTOR complex 1 (mTORC1)-dependent manner. Knocking down endogenous Rheb or applying rapamycin led to partial protection, identifying Rheb as a mediator of cell death. Ras and c-Raf kinase opposed the apoptotic effects induced by UV light or TNFα but did not prevent Rheb-mediated apoptosis. To gain structural insight into the signaling mechanisms, we determined the structure of Rheb-GDP by NMR. The complex adopts the typical canonical fold of RasGTPases and displays the characteristic GDP-dependent picosecond to nanosecond backbone dynamics of the switch I and switch II regions. NMR revealed Ras effector-like binding of activated Rheb to the c-Raf-Ras-binding domain (RBD), but the affinity was 1000-fold lower than the Ras/RBD interaction, suggesting a lack of functional interaction. shRNA-mediated knockdown of apoptosis signal-regulating kinase 1 (ASK-1) strongly reduced UV or TNFα-induced apoptosis and suppressed enhancement by Rheb overexpression. In conclusion, Rheb-mTOR activation not only promotes normal cell growth but also enhances apoptosis in response to diverse toxic stimuli via an ASK-1-mediated mechanism. Pharmacological regulation of the Rheb/mTORC1 pathway using rapamycin should take the presence of cellular stress into consideration, as this may have clinical implications.