29 research outputs found
On the Reference Structure for the Resonance Energy of Aromatic Hydrocarbons
To use the Zagreb Group and Aihara definition of resonance
energy, it is necessary that the roots of the reference polynomial
all be real. A partial proof that they are has been obtained in three
ways. Direct solution of the reference polynomial for annulenes
shows all roots real in this case. Application of Sturm sequences
promises the complete proof in principle, but requires the proof of
inequalities which we have so far resolved only for molecules with
four or fewer atoms. A graph theoretical approach succeeds for all
conjugated hydrocarbons in which no edge is shared by two rings.
It is also suggested that the reference polynomial may be used for
discriminating planar isospectral molecules
Bio-inspired Chemical Space Exploration of Terpenoids
Many computational methods are used to expand the open-ended border of chemical spaces. Natural products and their derivatives are an important source for drug discovery, and some algorithms are devoted to rapidly generating pseudo-natural products, while their accessibility and chemical interpretation were often ignored or underestimated, thus hampering experimental synthesis in practice. Herein, a bio-inspired strategy (named TeroGen) is proposed, in which the cyclization and decoration stage of terpenoid biosynthesis were mimicked by meta-dynamics simulations and deep learning models respectively, to explore their chemical space. In the protocol of TeroGen, the synthetic accessibility is validated by reaction energetics (reaction barrier and reaction heat) based on the GFN2-xTB methods. Chemical interpretation is an intrinsic feature as the reaction pathway is bioinspired and triggered by the RMSD-PP method in conjunction with an encoder-decoder architecture. This is quite distinct from conventional library/fragment-based or rule-based strategies, by using TeroGen, new reaction routes are feasibly explored to increase the structural diversity. For example, only a rather limited number of sesterterpenoids in our training set is included in this work, but our TeroGen would predict more than 30000 sesterterpenoids and map out the reaction network with super efficiency, ten times as many as the known sesterterpenoids (less than 2500). In sum, TeroGen not only greatly expands the chemical space of terpenoids but also provides various plausible biosynthetic pathways, which are crucial clues for heterologous biosynthesis, bio-mimic and chemical synthesis of complicated terpenoids
Diastereotopically Distinct Secondary Deuterium Kinetic Isotope Effects on the Thermal Isomerization of Cyclobutene to Butadiene
Diastereotopically Distinct Secondary Deuterium Kinetic Isotope Effects on the Thermal Isomerization of Cis-hexatriene to 1,3-cyclohexadiene
Biosynthesis of Spinosyn A: A [4 + 2] or [6 + 4] Cycloaddition?
SpnF,
one of the DielsāAlderases, produces spinosyn A, and
previous work demonstrated that its sole function is to catalyze the [4 + 2] cycloaddition (Fage, C. D.; et al. Nat. Chem. Biol. 2015, 11, 256ā258). Furthermore, the potential existence of a [6 +
4] cycloaddition bifurcation from previous theoretical
calculations on the nonenzyme model (Patel, A.; et al. J.
Am. Chem. Soc. 2016, 138, 3631ā3634) shows that the
exact mechanism of SpnF becomes even more interesting as well as now
being controversial. In the present work, QMĀ(DFT)/MM MD simulations
on the full enzyme model revealed three significant residues that
collaborate with other residues to control the direction of the cycloaddition,
namely, Tyr23, Thr196, and Trp256. These residues force the substrate
into a reactive conformation that causes the cycloaddition reaction
to proceed through a [4 + 2] pathway
instead of the [6 + 4] one. The mechanistic
insights deciphered here are fundamentally important for the rational
design of DielsāAlderases and biomimetic syntheses