Decoding the Reaction Mechanism of the Cyclocondensation of Ethyl acetate 2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl) polyazaheterocycle and Ethylenediamine using Bond Evolution Theory

The bonding evolution theory has been used to investigate the flow of electron density along the reaction pathways of ethyl acetate 2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl) polyazaheterocycle (1) and ethylenediamine (2). This reaction has three channels (1-3) and each one takes place via three or four steps. DFT results reveal that channel 2, which goes through imine intermediate is by far the most favorable one, and the main product 3 is more stable than 4 and 5, showing that this reaction is under kinetic and thermodynamic control, in clear agreement with the experimental outcomes. The BET analysis allows identifying unambiguously the main chemical events happening along channel 2. For this reaction channel, the mechanism along the first step (TS2-a) is described by a series of four structural stability domains (SSDs), while five SSDs are required for the second (TS2-b) and the third (TS2-c) one. The first step can be summarized as follow, the appearance of V(N1,C6) basin illustrating the formation of N1-C6 bond (SSD-II), the splitting of N1-H1 bond, followed by the restoration of the nitrogen N1 lone pair (SSD-III), and finally, the formation of the last O1-H1 bond (SSD-IV). For the second step, the formation of hydroxide ion is noted, consequent of the disappearance of V(C6,O7) basin, the transformation of C6-N1 single bond into double one (SSD-IV). Finally, the appearance of V(O7,H2) basin leading to the elimination of water molecule within the last domain. Overall, for the three reaction steps, the formation of the N-C bond appears always before the O-H one.

Jack D. Dunitz (1923–2021): a chemists’ crystallographer

Jack D. Dunitz (1923–2021) was Professor of Chemical Crystallography at the Swiss Federal Institute of Technology, Zurich. He received his degrees from Glasgow University, was at the ETH Zurich since 1957, and retired in 1990. His research interests included crystal structure analysis as a tool for solving chemical problems, polymorphism, solid state reactions, and a broad area of structural variations during chemical events under the umbrella term of structure correlation.

Using Dissipative Particle Dynamics to Model Effects of Chemical Reactions Occurring within Hydrogels

Computational models that reveal the structural response of polymer gels to changing, dissolved reactive chemical species would provide useful information about dynamically evolving environments. However, it remains challenging to devise one computational approach that can capture all the interconnected chemical events and responsive structural changes involved in this multi-stage, multi-component process. Here, we augment the dissipative particle dynamics (DPD) method to simulate the reaction of a gel with diffusing, dissolved chemicals to form kinetically stable complexes, which in turn cause concentration-dependent deformation of the gel. Using this model, we also examine how the addition of new chemical stimuli and subsequent reactions cause the gel to exhibit additional concentration-dependent structural changes. Through these DPD simulations, we show that the gel forms multiple latent states (not just the “on/off”) that indicate changes in the chemical composition of the fluidic environment. Hence, the gel can actuate a range of motion within the system, not just movements corresponding to the equilibrated swollen or collapsed states. Moreover, the system can be used as a sensor, since the structure of the layer effectively indicates the presence of chemical stimuli.

Nuclear Singlet Relaxation by Chemical Exchange

The population imbalance between nuclear singlet states and triplet states of strongly coupled spin-1/2 pairs, also known as nuclear singlet order, is well protected against several common relaxation mechanisms. We study the nuclear singlet relaxation of 13C pairs in aqueous solutions of 1,2-13C2 squarate, over a range of pH values. The 13C singlet order is accessed by introducing 18O nuclei in order to break the chemical equivalence. The squarate dianion is in chemical equilibrium with hydrogen-squarate (SqH−) and squaric acid (SqH2) characterised by the dissociation constants pKa1 = 1:5 and pKa2 = 3:4. Surprisingly, we observe a striking increase in the singlet decay time constants TS when the pH of the solution exceeds ~ 10, which is far above the acid-base equilibrium points. We derive general rate expressions for chemical-exchange-induced nuclear singlet relaxation and provide a qualitative explanation of the TS behaviour of the squarate dianion. We identify a kinetic contribution to the singlet relaxation rate constant which depends explicitly on kinetic rate constants. Qualitative agreement is achieved between the theory and the experimental data. This study shows that infrequent chemical events may have a strong effect on the relaxation of nuclear singlet order.

The Mechanism of Rubisco Catalyzed Carboxylation Reaction: Chemical Aspects Involving Acid-Base Chemistry and Functioning of the Molecular Machine

In recent years, a great deal of attention has been paid by the scientific community to improving the efficiency of photosynthetic carbon assimilation, plant growth and biomass production in order to achieve a higher crop productivity. Therefore, the primary carboxylase enzyme of the photosynthetic process Rubisco has received considerable attention focused on many aspects of the enzyme function including protein structure, protein engineering and assembly, enzyme activation and kinetics. Based on its fundamental role in carbon assimilation Rubisco is also targeted by the CO2-fertilization effect, which is the increased rate of photosynthesis due to increasing atmospheric CO2-concentration. The aim of this review is to provide a framework, as complete as possible, of the mechanism of the RuBP carboxylation/hydration reaction including description of chemical events occurring at the enzyme “activating” and “catalytic” sites (which involve Broensted acid-base reactions) and the functioning of the complex molecular machine. Important research results achieved over the last few years providing substantial advancement in understanding the enzyme functioning will be discussed.

Helium in diamonds unravels over a billion years of craton metasomatism

Chemical events involving deep carbon- and water-rich fluids impact the continental lithosphere over its history. Diamonds are a by-product of such episodic fluid infiltrations, and entrapment of these fluids as microinclusions in lithospheric diamonds provide unique opportunities to investigate their nature. However, until now, direct constraints on the timing of such events have not been available. Here we report three alteration events in the southwest Kaapvaal lithosphere using U-Th-He geochronology of fluid-bearing diamonds, and constrain the upper limit of He diffusivity (to D ≈ 1.8 × 10−19 cm2 s−1), thus providing a means to directly place both upper and lower age limits on these alteration episodes. The youngest, during the Cretaceous, involved highly saline fluids, indicating a relationship with late-Mesozoic kimberlite eruptions. Remnants of two preceding events, by a Paleozoic silicic fluid and a Proterozoic carbonatitic fluid, are also encapsulated in Kaapvaal diamonds and are likely coeval with major surface tectonic events (e.g. the Damara and Namaqua–Natal orogenies).

Unraveling the energetic significance of chemical events in enzyme catalysis via machine-learning based regression approach

The bacterial enzyme class of β-lactamases are involved in benzylpenicillin acylation reactions, which are currently being revisited using hybrid quantum mechanical molecular mechanical (QM/MM) chain-of-states pathway optimizations. Minimum energy pathways are sampled by reoptimizing pathway geometry under different representative protein environments obtained through constrained molecular dynamics simulations. Predictive potential energy surface models in the reaction space are trained with machine-learning regression techniques. Herein, using TEM-1/benzylpenicillin acylation reaction as the model system, we introduce two model-independent criteria for delineating the energetic contributions and correlations in the predicted reaction space. Both methods are demonstrated to effectively quantify the energetic contribution of each chemical process and identify the rate limiting step of enzymatic reaction with high degrees of freedom. The consistency of the current workflow is tested under seven levels of quantum chemistry theory and three non-linear machine-learning regression models. The proposed approaches are validated to provide qualitative compliance with experimental mutagenesis studies.

Solution Structure of a Europium-Nicotianamine Complex Supports That Phytosiderophores Bind Lanthanides

We report the solution structure of a europium-nicotianamine complex predicted from ab initio molecular dynamics simulations with density functional theory. Emission and excitation spectroscopy measurements show that the Eu³⁺coordination environment changes in the presence of nicotianamine, suggesting complex formation, and strongly supporting the predicted Eu³⁺-nicotianamine complex structure from computation. We used our recently optimized pseudopotentials and basis sets for lanthanides to model Eu³⁺-ligand complexes with explicit water molecules in periodic boxes, effectively simulating the solution phase. Our simulations consider possible chemical events (e.g. coordination bond formation, protonation state changes, charge transfers), as well as ligand flexibility and solvent rearrangements. Our computational approach correctly predicts the solution structure of a Eu³⁺-ethylenediaminetetraacetic acid complex within 0.05 Å of experimentally measured values, backing the fidelity of the predicted solution structure of the Eu³⁺-nicotianamine complex. Emission and excitation spectroscopy measurements were also performed on the well-known Eu³⁺-ethylenediaminetetraacetic acid complex to validate our experimental methods. The electronic structure of the Eu³⁺-nicotianamine complex is analyzed to describe electron densities and coordination bonds in greater detail. Nicotianamine is a metabolic precursor of, and structurally very similar to, phytosiderophores, which are responsible for the uptake of metals in plants. Although knowledge that nicotianamine binds europium does not determine how plants uptake rare earths from the environment, it strongly supports that phytosiderophores bind lanthanides.

Solution Structure of a Europium-Nicotianamine Complex Supports That Phytosiderophores Bind Lanthanides

We report the solution structure of a europium-nicotianamine complex predicted from ab initio molecular dynamics simulations with density functional theory. Emission and excitation spectroscopy measurements show that the Eu³⁺coordination environment changes in the presence of nicotianamine, suggesting complex formation, and strongly supporting the predicted Eu³⁺-nicotianamine complex structure from computation. We used our recently optimized pseudopotentials and basis sets for lanthanides to model Eu³⁺-ligand complexes with explicit water molecules in periodic boxes, effectively simulating the solution phase. Our simulations consider possible chemical events (e.g. coordination bond formation, protonation state changes, charge transfers), as well as ligand flexibility and solvent rearrangements. Our computational approach correctly predicts the solution structure of a Eu³⁺-ethylenediaminetetraacetic acid complex within 0.05 Å of experimentally measured values, backing the fidelity of the predicted solution structure of the Eu³⁺-nicotianamine complex. Emission and excitation spectroscopy measurements were also performed on the well-known Eu³⁺-ethylenediaminetetraacetic acid complex to validate our experimental methods. The electronic structure of the Eu³⁺-nicotianamine complex is analyzed to describe electron densities and coordination bonds in greater detail. Nicotianamine is a metabolic precursor of, and structurally very similar to, phytosiderophores, which are responsible for the uptake of metals in plants. Although knowledge that nicotianamine binds europium does not determine how plants uptake rare earths from the environment, it strongly supports that phytosiderophores bind lanthanides.