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Related Concept Videos

Complexation Equilibria: The Chelate Effect01:19

Complexation Equilibria: The Chelate Effect

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In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Complexation Equilibria: Factors Influencing Stability of Complexes01:09

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In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
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Formation of Complex Ions03:45

Formation of Complex Ions

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A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
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Complexation Equilibria: Overview01:23

Complexation Equilibria: Overview

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Complexation reactions take place when dative or coordinate covalent bonds form between metal ions and ligands. The compounds formed in these reactions are called coordination compounds. The number of bonds formed between the metal ion and the ligands is called its coordination number. Generally, most metal ions in an aqueous solution are solvated by water molecules and thus exist as aqua complexes.
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Complexometric Titration: Ligands00:43

Complexometric Titration: Ligands

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Different monodentate and polydentate ligands are used as complexing agents in complexometric titration reactions. The formation of complexes by mono- and bidentate ligands involves two or more intermediate steps, limiting their use as complexing agents. In comparison, polydentate ligands can form complexes with metal ions in a single-step process, facilitating sharper end points. This means polydentate ligands, such as amino carboxylic acid derivatives, are most commonly employed in...
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Updated: Jan 7, 2026

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
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Conformation-Dependent Complexation Interactions for a SMARCA2 PROTAC and Cyclodextrin.

Matthew N O'Brien Laramy1, José G Napolitano1, Yuhui Zhou2

  • 1Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

Molecular Pharmaceutics
|December 20, 2025
PubMed
Summary
This summary is machine-generated.

Protein degraders, or proteolysis targeting chimeras (PROTACs), exhibit unique conformational properties influencing their solubility. Understanding these PROTAC conformations is key for effective formulation and drug development.

Keywords:
PROTACsSMARCA2conformationcyclodextrinprotein degraderssolubilitytargeted protein degradation

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Exploring Protein-Glycan Interactions: Advances in Nuclear Magnetic Resonance
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Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Pharmaceutical Sciences

Background:

  • Bivalent protein degraders, known as proteolysis targeting chimeras (PROTACs), represent a novel therapeutic approach.
  • PROTACs possess unique physicochemical and structural characteristics that can impede biopharmaceutical properties like solubility, complicating drug development.
  • Limited research exists on formulation strategies specifically tailored for PROTACs to address these challenges.

Purpose of the Study:

  • To investigate the solubilization mechanisms of a VHL-based PROTAC (A515) targeting SMARCA2.
  • To elucidate the role of molecular conformation and stereochemistry in PROTAC solubility and formulation.

Main Methods:

  • Utilized Nuclear Magnetic Resonance (NMR) spectroscopy techniques.
  • Employed isothermal titration calorimetry (ITC).
  • Conducted quantitative solubility measurements.

Main Results:

  • A515 exists in two distinct conformational populations in aqueous solution, differing in amide group rotation (trans-proline and cis-proline isomers).
  • The trans-proline isomer adopts open conformations with larger hydrodynamic size, while the cis-proline isomer forms condensed conformations with smaller hydrodynamic size.
  • The solubilization efficiency of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) varies between these populations, influenced by the accessibility of A515's terminal regions.

Conclusions:

  • Conformation and stereochemistry play a critical, previously unreported role in the rational formulation design of PROTACs.
  • Distinct conformational populations of PROTACs exhibit differential responses to solubilizing excipients like HP-β-CD.
  • These findings provide specific considerations for formulating VHL-based PROTACs to enhance solubility.