1. Redox-enhanced hemilability of a tris(tert-butoxy)siloxy ligand at cerium
Jochen Friedrich, Yusen Qiao, Cäcilia Maichle-Mössmer, Eric J Schelter, Reiner Anwander Dalton Trans. 2018 Jul 31;47(30):10113-10123. doi: 10.1039/c8dt01878b.
The stabilizing effect of a tris(tert-butoxy)siloxy ligand on cerium(iv) is revealed by electrochemical and computation methods as well as by targeted redox chemistry. Ceric homoleptic complex Ce[OSi(OtBu)3]4 was obtained by the reaction of [Et4N]2[CeCl6] with NaOSi(OtBu)3 at ambient temperature in acetonitrile, while cerous ion-separated complex [Ce{OSi(OtBu)3}4][K(2.2.2-crypt)] was readily synthesized from [Ce{OSi(OtBu)3}4K] and cryptand. The solid-state structures of monocerium complexes Ce[OSi(OtBu)3]4 and Ce[OSi(OtBu)3]4(THF) show 5- and 6-coordinate CeIV centers (one κ2-bonded siloxy ligand), while complex [Ce{OSi(OtBu)3}4][K(2.2.2-crypt)] exhibits a 4-coordinate CeIII center (all-terminal siloxy coordination). A comparative electrochemical study of Ce[OSi(OtBu)3]4 and [Ce{OSi(OtBu)3}4][K(2.2.2-crypt)] suggests a redox-modulated molecular rearrangement process, featuring oxidation-state dependent formation and release of a CeOtBu coordination. While the overall stabilization of CeIV by the siloxy ligand is evident, significant extra stabilization is gained if the siloxy ligand coordinates in a chelating fashion, which is further supported by DFT calculations. Natural bond orbital (NBO) analysis indicates an enhanced donation of the siloxy ligand electron density into the unfilled CeIV 6s, 4f, and 5d orbitals. CeIV to CeIII reduction readily occurs when homoleptic complex Ce[OSi(OtBu)3]4 is treated with cobaltocene, affording the separated ion pair [Ce{OSi(OtBu)3}4][CoCp2], featuring exclusive terminal siloxy bonding in the solid-state, similar to that detected for [Ce{OSi(OtBu)3}4][K(2.2.2-crypt)].
2. The peptide Z-Aib-Aib-Aib-L-Ala-OtBu
Renate Gessmann, Hans Brückner, Kyriacos Petratos Acta Crystallogr C Struct Chem. 2014 Apr;70(Pt 4):405-7. doi: 10.1107/S2053229614005567. Epub 2014 Mar 21.
The title peptide, N-benzyloxycarbonyl-α-aminoisobutyryl-α-aminoisobutyryl-α-aminoisobutyryl-L-alanine tert-butyl ester or Z-Aib-Aib-Aib-L-Ala-OtBu (Aib is α-aminoisobutyric acid, Z is benzyloxycarbonyl and OtBu indicates the tert-butyl ester), C27H42N4O7, is a left-handed helix with a right-handed conformation in the fourth residue, which is the only chiral residue. There are two 4→1 intramolecular hydrogen bonds in the structure. In the lattice, molecules are hydrogen bonded to form columns along the c axis.
3. Hybrid Arborescent Polypeptide-Based Unimolecular Micelles: Synthesis, Characterization, and Drug Encapsulation
Basma Mahi, Mario Gauthier, Nikos Hadjichristidis Biomacromolecules. 2022 Jun 13;23(6):2441-2458. doi: 10.1021/acs.biomac.2c00202. Epub 2022 May 19.
This paper reports novel hybrid arborescent polypeptides based on poly(γ-benzyl l-glutamate)-co-poly(γ-tert-butyl l-glutamate)-g-polysarcosine [P(BG-co-Glu(OtBu))-g-PSar]. The synthesis is launched by ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl l-glutamate (BG-NCA) and γ-tert-butyl l-glutamate (Glu(OtBu)-NCA) to synthesize a random copolymer P(BG-co-Glu(OtBu)) serving as a precursor for the arborescent system, followed by deprotection of the tert-butyl (tBu) groups to afford free COOH moieties serving as coupling sites. Two copolymerization reactions were carried out to afford the side chains. One type of side chain was a random copolymer P(BG-co-Glu(OtBu)), while the other type was a triblock copolymer PGlu(OtBu)-b-PBG-b-PGlu(OtBu). The peptide coupling reactions were conducted between the COOH moieties on the precursor and the terminus amine on the chain end of the P(BG-co-Glu(OtBu)) random copolymer or the PGlu(OtBu)-b-PBG-b-PGlu(OtBu) triblock copolymer to obtain G0 polymers. Afterward, hydrolyzing the tBu moieties of the G0 substrates yielded randomly functionalized G0 and end-functionalized G0. Randomly functionalized G0 was used as a substrate for the next generation G1 (randomly functionalized and end-functionalized G1 after deprotection) or coated with polysarcosine (PSar) to gain G0-g-PSar. The G0 substrate prepared with the triblock copolymer PGlu(OtBu)-b-PBG-b-PGlu(OtBu) was only grafted with PSar after deprotection, resulting in G0-eg-PSar. Depending on the functionality mode of the G1 substrate, the PSar coating yielded two different graft polymers, G1-g-PSar and G1-eg-PSar, for randomly functionalized and end-functionalized G1, respectively. The PSar hydrophilic shell was decorated with the sequence of (arginine, glycine, and aspartic acid) tripeptides (RGD) as a targeting ligand to improve the potentiality of the arborescent unimolecular micelles as drug carriers. Preparative size exclusion chromatography (SEC) was used to fractionate these complex macromolecular architectures. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Raman spectroscopy, and SEC were used for molecular characterization of all intermediate and final products and dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) for micellar characterization. A comparison between randomly grafted (g) and end-grafted (eg) unimolecular micelles demonstrates that the former has an undefined core-shell structure, unlike its end-grafted analog. In addition, this study has proved that decoration of the shell with RGD contributed to avoiding micelle aggregation but limited chemotherapy agent encapsulation. However, more than their naked analog, the sustained release was noticeable in decorated micelles. Doxorubicin was utilized as a chemotherapy model, and loading was achieved successfully by physical entrapment.
