Effective Molarity Redux: Proximity as a Guiding Force in Chemistry and Biology

Abstract

The cell interior is a complex and demanding environment. An incredible variety of molecules jockey to identify the correct position–the specific interactions that promote biology that are hidden among countless unproductive options. Ensuring that the business of the cell is successful requires sophisticated mechanisms to impose temporal and spatial specificity–both on transient interactions and their eventual outcomes. Two strategies employed to regulate macromolecular interactions in a cellular context are co-localization and compartmentalization. Macromolecular interactions can be promoted and specified by localizing the partners within the same subcellular compartment, or by holding them in proximity through covalent or non-covalent interactions with proteins, lipids, or DNA– themes that are familiar to any biologist. The net result of these strategies is an increase in effective molarity: the local concentration of a reactive molecule near its reaction partners. We will focus on this general mechanism, employed by Nature and adapted in the lab, which allows delicate control in complex environments: the power of proximity to accelerate, guide, or otherwise influence the reactivity of signaling proteins and the information that they encode.

Dual‐Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic Supramolecular Wires

“…The ΔΔ G o values can be used to calculate the effective molarity (EM) for the appended ODNs on the supramolecular wire. In this case, the EM is a quantitative parameter for the evaluation of the chelate cooperative effect in DNA‐duplex formation.…”

Artificial Signal Transduction Therapy: A Futuristic Approach to Disease Treatment

“…A common feature of the systems above is their ability to bring the desired interacting partners in proximity, which increases their effective molarity [19]. Whereas this principle is frequently applied in natural signal transduction pathways, this is not the only mechanism used to transduce the signal.…”

Effective molarity in a nucleic acid-controlled reaction

“…12 The concept of “effective molarity” provides a quantitative method for expressing the extent to which enforced proximity favors a given unimolecular process over the corresponding bi-molecular counterpart. 3,9,12 Mathematically, this value is simply the rate or equilibrium constant of the unimolecular process divided by that of a bi-molecular comparator reaction (k uni s −1 /k bi M −1 •s −1 ). 3,9,12 The resulting value (obtained in units of molarity) represents the theoretical reagent concentration at which the observed (pseudo-first-order) rate or equilibrium constant of the second-order process would match that of the unimolecular process.…”

“…3,9,12 Mathematically, this value is simply the rate or equilibrium constant of the unimolecular process divided by that of a bi-molecular comparator reaction (k uni s −1 /k bi M −1 •s −1 ). 3,9,12 The resulting value (obtained in units of molarity) represents the theoretical reagent concentration at which the observed (pseudo-first-order) rate or equilibrium constant of the second-order process would match that of the unimolecular process. Effective molarities have been measured for a significant number of enzymatic processes, intramolecular organic reactions, and templated reactions involving small organic molecules.…”

“…Effective molarities have been measured for a significant number of enzymatic processes, intramolecular organic reactions, and templated reactions involving small organic molecules. 3,5,6,8,9,12 …”