Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)–Nitrosyl Complex

Abstract

Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time‐dependent dynamics to discriminate the endogenous and exogenous inputs. For a real‐time stimulation of cell signaling, we synthesized a photo‐cleavable metal–nitrosyl complex, [CoIII(MDAP)(NO)(CH3CN)]2+ (MDAP=N,N′‐dimethyl‐2,11‐diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal‐regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems.

Bent and Linear {CoNO}8 Entities: Structure and Bonding in a Prototypic Class of Nitrosyls

“…Prior to an inclusion of triplets in the discussion, the small size of the [Co(NH 3 ) 4 (NO)] 2+ species was used to check the dependence of charges and OS assignments from the applied method. In particular, because the small active (8, 7) space of the larger systems had kept us from deriving more quantitative results, except the antibond population, the larger (12,14) active space was included. This configuration space contains 14 orbitals: five Co(3d) orbitals, five Co(4d) second-shell orbitals, two N−O π* orbitals, the nitrosyl donor orbital (3σ in NO's MO scheme), and the major cobalt−ammine bonding orbital.…”

“…Complete-active-space self-consistent-field CASSCF(8,7) calculations were used for illustrative purposes because of the more localized nature of molecular orbitals (MOs) by this wavefunction approach and, essentially, to show the nitrosyl−metal typical amount of static correlation in terms of antibonding population. A larger active space was included in a CASSCF (12,14) approach on two isomers of the small species [Co(NH 3 ) 4 (NO)] 2+ , as well as CCSD single-point calculations. There, also various density functionals were employed to evaluate the dependence of the charges and OSs from the level of theory.…”

Photoinduced NO and HNO Production from Mononuclear {FeNO}6 Complex Bearing a Pendant Thiol

“…Nitric oxide (NO) and its one-electron reduced derivative nitroxyl (HNO/NO – ) play significant roles in many physiological processes. − The target receptors of NO and HNO/NO – often contain iron centers (heme or nonheme) or sulfur ligands (thiol or thiolate), leading to the formation of NO adducts responsible for biological processes. , For example, the formation of cyclic guanosine monophosphate (cGMP) triggered by binding of NO to the iron-heme center in soluble guanylate cyclase (sGC) represents a key step for neuromodulation or vasodilation. , HNO also induces a vasorelaxation response and displays a more vasodilative effect than NO, thereby showing promise as a positive cardiac inotrope for heart failure treatment. , Inspired by the importance of NO and HNO in biological systems or medical applications, many efforts have been made to prepare NO- or HNO-releasing agents based on metal–NO compounds. − The release of NO from exogenous metal–nitrosyl sources can be stimulated by changes in pH, solvation, heat, and light. ,− In contrast with the NO-releasing chemistry from metal–nitrosyl sources, the generation of HNO from metal–nitroxyl species (M­(HNO/NO – )) remains relatively unexplored. It is generally proposed that the reduction of the iron–NO complexes, {FeNO} x ( x = 6 or 7; the Enemark–Felthan notation), to electron-rich {FeNO} 8 species is an essential step in HNO-releasing chemistry. − Subsequent protonation of the Fe-bound NO species carrying a more likely NO – character would yield the formation of HNO. − However, protonation of the {FeNO} 8 species by adventitious proton sources frequently results in the formation of corresponding {FeNO} 7 species and H 2 . − …”

A new photoactivable NO‐releasing {Ru−NO}6 ruthenium nitrosyl complex with a tetradentate ligand containing aniline and pyridine moieties

“…The photochemical quantum yield of the NO photolysis (Φ NO ) of 1 was determined by using the standard ferrioxalate actinometry. [44,45] Compound 1 in various solvents, including C 2 H 5 OH, CHCl 3 , DMSO, CH 3 CN, and CH 3 NO 2 , respectively, was photoirradiated with a 300 W xenon lamp through a 400 (� 5) nm bandpass filter (photon flux = 4.2 × 10 À 9 einstein s À 1 ). The NO photolysis was quantitated by monitoring the absorbance changes at 515, 525, 510, 560, and 550 nm for C 2 H 5 OH, CHCl 3 , DMSO, CH 3 CN, and CH 3 NO 2 solutions, respectively.…”

“…The quantum yields for NO photolysis (Φ NO ) of 1 were determined, following the previous methods with modifications. [31,41,44,45] Compound 1 was dissolved in C 2 H 5 OH, CHCl 3 , DMSO, CH 3 CN, and CH 3 NO 2 , respectively, to a concentration of 2.5 × 10 À 4 M. The sample solutions were delivered to 3 mL quartz cuvettes and deaerated by bubbling Ar. The solution was, then, photoirradiated with a xenon lamp (300 W, MAX-302, Asahi spectra Co.) through a 400 (� 5) nm bandpass filter.…”