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Redox Allosteric Control – New communication in JACS


The Weak Link Approach (WLA) is a successful strategy for allosterically controlling the formation of cavities¹ and the access to them² through the action of reversible hemilabile-bond formation around an organometallic center. Thus far, the WLA has been used to mimic biological cavities whose access is controlled chemically as in the scheme shown below which belongs to a previous WLA work published in 2014, my first time involved in the calculation of bond energies for hemilabile groups.

Screenshot from 2018-10-29 22:57:15

Mendez-Arroyo et al. JACS (2014) 136, 10340-10348

Chiefly developed by the Chad Mirkin group at Northwestern, the WLA has now reached a new milestone in which the allosteric control is further coupled to a redox equilibrium which alters the strength of the hemilabile bonds. These findings are reported in JACS as a communication (DOI: 10.1021/jacs.8b09321). Previous efforts were unsuccessful due to the instability of the oxidized species, which makes regulation challenging. A ferrocenyl (Fc) group was attached to the hemilabile ligand to provide the redox center which can further assist and control the ring opening via an increment in the electrostatic repulsion of the two metallic centers. Thus, the weak-link is displaced by exogenous ligands only after the Fc group was oxidized.

ja-2018-09321y_0006

Bond strengths for the hemilabile bonds were calculated at the ω-B97XD/lanl2dz level of theory upon optimized structures. Relative energies were calculated through the thermochemistry analysis (freq=noraman) made by Gaussian09 and the bond strengths were calculated with the NBODel procedure included in NBO3.1. In the open configurations we found that upon oxidation of Fc the exogenous ligand bond to Pt(II) strengthens by a few kcal/mol (2 – 10), however the Fe(III)-P distance increases and that can be observed via ³¹P NMR spectroscopy.

For the non-oxidized complexes, the HOMO’s are largely composed of the ferrocene highest energy orbitals, which is susceptible of being oxidized, whereas the LUMO’s are located throughout the organometallic fragment. When Ferrocene is oxidized to Ferrocenium, the situation is reversed and now HOMO’s are found spread over the organometallic fragment and the LUMO’s over ferrocenium; all of which is coherent with the idea of Fc now being able to be reduced. Plots for the HOMO LUMO orbitals for compound (6) in the Reduced (Fe2) and Oxidized (Fe3) states are shown (alpha and beta density are shown separately in the latter case).

 

Thanks to Prof. Chad Mirkin, Dr. Andrea d’Aquino, and Edmund Cheng for letting me be a part of this project.

[1] D’Aquino, A. I., Cheng, H. F., Barroso-Flores, J., Kean, Z. S., Mendez-Arroyo, J., McGuirk, C. M., & Mirkin, C. A. (2018). An Allosterically Regulated, Four-State Macrocycle. Inorganic Chemistry, 57(7), 3568–3578.
[2] Mendez-Arroyo, J., Barroso-Flores, J., Lifschitz, A. M., Sarjeant, A. a., Stern, C. L., & Mirkin, C. a. (2014). A multi-state, allosterically-regulated molecular receptor with switchable selectivity. Journal of the American Chemical Society, 136(29), 10340–10348.

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New paper in JACS


Well, I only contributed with the theoretical section by doing electronic structure calculations, so it isn’t really a paper we can ascribe to this particular lab, however it is really nice to see my name in JACS along such a prominent researcher as Prof. Chad Mirkin from Northwestern University, in a work closely related to my area of research interest as macrocyclic recognition agents.

In this manuscript, a calix[4]arene is allosterically opened and closed reversibly by coordinating different kinds of ligands to a platinum center linked to the macrocycle. (This approach has been referred to as the weak link approach.) I recently visited Northwestern and had a great time with José Mendez-Arroyo, the first author, who showed me around and opened the possibility for further work between our research groups.

(Ligands: Green = Chloride; Blue = Cyanide)

Closed, semi-open and fully open conformations; selectivity is modulated through cavity size. (Ligands: Green = Chloride; Blue = Cyanide)

Here at UNAM we calculated the interaction energies for the two guests that were successfully inserted into the cavity: N-methyl-pyridinium (Eint = 57.4 kcal/mol) and Pyridine-N-oxide (Eint = +200.0 kcal/mol). Below you can see the electrostatic potential mapped onto the electron density isosurface for one of the adducts. Relative orientation of the hosts within the cavity follows the expected (anti-) alignment of mutual dipole moments. At this level of theory, we could easily be inclined to assert that the most stable interaction is indeed the one from the semi-open compound and that this in turn is due to the fact that host and guest are packed closer together but there is also an orbital issue: Pyridine Oxide is a better electron acceptor than N-Me-pyridinium and when we take a closer look to the (Natural Bonding) orbitals interacting it becomes evident that a closer location does not necessarily yields a stronger interaction when the electron accepting power of the ligand is weaker (which is, in my opinion, both logic and at the same time a bit counterintuitive, yet fascinating, nonetheless).

Electrostatic potential mapped onto the electron density surface of one of the aducts under study

Electrostatic potential mapped onto the electron density surface of one of the adducts under study

All calculations were performed at the B97D/LANL2DZ level of theory with the use of Gaussian09 and NBO3.1 as provided within the former. Computing time at UNAM’s supercomputer known as ‘Miztli‘ is fully acknowledged.

The full citation follows:

A Multi-State, Allosterically-Regulated Molecular Receptor With Switchable Selectivity
Jose Mendez-Arroyo Joaquín Barroso-Flores §,Alejo M. Lifschitz Amy A. Sarjeant Charlotte L. Stern , and Chad A. Mirkin *

J. Am. Chem. Soc., Article ASAP
DOI: 10.1021/ja503506a
Publication Date (Web): July 9, 2014

 Thanks to José Mendez-Arroyo for contacting me and giving me the opportunity to collaborate with his research; I’m sure this is the first of many joint projects that will mutually benefit our groups. 

 

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