4 research outputs found
Roughness of Molecular Property Landscapes and Its Impact on Modellability
In molecular discovery and drug design, structure–property
relationships and activity landscapes are often qualitatively or quantitatively
analyzed to guide the navigation of chemical space. The roughness
(or smoothness) of these molecular property landscapes is one of their
most studied geometric attributes, as it can characterize the presence
of activity cliffs, with rougher landscapes generally expected to
pose tougher optimization challenges. Here, we introduce a general,
quantitative measure for describing the roughness of molecular property
landscapes. The proposed roughness index (ROGI) is loosely inspired
by the concept of fractal dimension and strongly correlates with the
out-of-sample error achieved by machine learning models on numerous
regression tasks
<i>In silico</i> Design of Supramolecules from Their Precursors: Odd–Even Effects in Cage-Forming Reactions
We synthesize a series of imine cage
molecules where increasing
the chain length of the alkanediamine precursor results in an odd–even
alternation between [2 + 3] and [4 + 6] cage macrocycles. A computational
procedure is developed to predict the thermodynamically preferred
product and the lowest energy conformer, hence rationalizing the observed
alternation and the 3D cage structures, based on knowledge of the
precursors alone
<i>In silico</i> Design of Supramolecules from Their Precursors: Odd–Even Effects in Cage-Forming Reactions
We synthesize a series of imine cage
molecules where increasing
the chain length of the alkanediamine precursor results in an odd–even
alternation between [2 + 3] and [4 + 6] cage macrocycles. A computational
procedure is developed to predict the thermodynamically preferred
product and the lowest energy conformer, hence rationalizing the observed
alternation and the 3D cage structures, based on knowledge of the
precursors alone
Controlling the Crystallization of Porous Organic Cages: Molecular Analogs of Isoreticular Frameworks Using Shape-Specific Directing Solvents
Small structural changes in organic
molecules can have a large
influence on solid-state crystal packing, and this often thwarts attempts
to produce isostructural series of crystalline solids. For metal–organic
frameworks and covalent organic frameworks, this has been addressed
by using strong, directional intermolecular bonding to create families
of isoreticular solids. Here, we show that an organic directing solvent,
1,4-dioxane, has a dominant effect on the lattice energy for a series
of organic cage molecules. Inclusion of dioxane directs the crystal
packing for these cages away from their lowest-energy polymorphs to
form isostructural, 3-dimensional diamondoid pore channels. This is
a unique function of the size, chemical function, and geometry of
1,4-dioxane, and hence, a noncovalent auxiliary interaction assumes
the role of directional coordination bonding or covalent bonding in
extended crystalline frameworks. For a new cage, <b>CC13</b>, a dual, interpenetrating pore structure is formed that doubles
the gas uptake and the surface area in the resulting dioxane-directed
crystals