Organometallic Chemistry Tools for Building Biologically Relevant Nanoscale Systems.

The recent emergence of organometallic chemistry for modification of biomolecular nanostructures has begun to rewrite the long-standing assumption among practitioners that small-molecule organometallics are fundamentally incompatible with biological systems. This Perspective sets out to clarify some of the existing misconceptions by focusing on the growing organometallic toolbox for biomolecular modification. Specifically, we highlight key organometallic transformations in constructing complex biologically relevant systems on the nanomolecular scale, and the organometallic synthesis of hybrid nanomaterials composed of classical nanomaterial components combined with biologically relevant species.

Organometallic Oxidative Addition Complexes for -Arylation of Free Cysteines.

Development of bioconjugation strategies to efficiently modify biomolecules is of key importance for fundamental and translational scientific studies. Cysteine -arylation is an approach which is becoming more popular due to generally rapid kinetics and high chemoselectivity, as well as the strong covalently bonded -aryl linkage created in these processes. Organometallic approaches to cysteine -arylation have been explored that feature many advantages compared to their more traditional organic counterparts.

Ultrafast Au(III)-Mediated Arylation of Cysteine.

Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down to picomolar concentrations and allow for the rapid construction of complex heterostructures from peptides, proteins, and oligonucleotides. This work showcases how organometallic chemistry can be interfaced with biomolecules and lead to a range of reactivities that are largely unmatched by classical organic chemistry tools.

Organometallic -arylation Reagents for Rapid PEGylation of Biomolecules.

Bioconjugation techniques for biomolecule-polymer conjugation are numerous; however, slow kinetics and steric challenges generally necessitate excess reagents or long reaction times. Organometallic transformations are known to circumvent these issues; yet, harsh reaction conditions, incompatibility in aqueous media, and substrate promiscuity often limit their use in a biological context. The work reported herein demonstrates a facile and benign organometallic Au(III) -arylation approach that enables the synthesis of poly(ethylene glycol) monomethyl ether (mPEG)-protein conjugates with high efficiency.

Simple steps to enable reproducibility: culture conditions affecting Chlamydomonas growth and elemental composition.

Even subtle modifications in growth conditions elicit acclimation responses affecting the molecular and elemental makeup of organisms, both in the laboratory and in natural habitats. We systematically explored the effect of temperature, pH, nutrient availability, culture density, and access to CO and O in laboratory-grown algal cultures on growth rate, the ionome, and the ability to accumulate Fe. We found algal cells accumulate Fe in alkaline conditions, even more so when excess Fe is present, coinciding with a reduced growth rate.

An Organometallic Strategy for Cysteine Borylation.

Synthetic bioconjugation at cysteine (Cys) residues in peptides and proteins has emerged as a powerful tool in chemistry. Soft nucleophilicity of the sulfur in Cys renders an exquisite chemoselectivity with which various functional groups can be placed onto this residue under benign conditions. While a variety of reactions have been successful at producing Cys-based bioconjugates, the majority of these feature sulfur-carbon bonds.

Preparation of Biomolecule-Polymer Conjugates by Grafting-From Using ATRP, RAFT, or ROMP.

Biomolecule-polymer conjugates are constructs that take advantage of the functional or otherwise beneficial traits inherent to biomolecules and combine them with synthetic polymers possessing specially tailored properties. The rapid development of novel biomolecule-polymer conjugates based on proteins, peptides, or nucleic acids has ushered in a variety of unique materials, which exhibit functional attributes including thermo-responsiveness, exceptional stability, and specialized specificity. Key to the synthesis of new biomolecule-polymer hybrids is the use of controlled polymerization techniques coupled with either grafting-from, grafting-to, or grafting-through methodology, each of which exhibit distinct advantages and/or disadvantages.

Regulating Transition-Metal Catalysis through Interference by Short RNAs.

Herein we report the discovery of a Au -DNA hybrid catalyst that is compatible with biological media and whose reactivity can be regulated by small complementary nucleic acid sequences. The development of this catalytic system was enabled by the discovery of a novel Au -mediated base pair. We found that Au binds DNA containing C-T mismatches.