Stabilizing Effect of a 4c/6e Hypervalent Bond in Dinitrodiphenyl Disulfides and Their Thermochemical Properties: Experimental and Computational Approach.

Thermochemical properties and intramolecular interactions of 2,2'-dinitrodiphenyl disulfide (2DNDPDS) and 4,4'-dinitrodiphenyl disulfide (4DNDPDS) were determined and analyzed. Their standard molar formation enthalpies in the gas phase (ΔfHm°(g)'s) were experimentally determined; theoretically, they were computed using the G4 composite method and atomization reactions. Specifically, ΔfHm°(g)'s were obtained by combining formation enthalpies in the condensed phase and enthalpies of phase change. Formation enthalpies in the condensed phase were determined experimentally through combustion energies, which in turn were found by means of a rotatory bomb combustion calorimeter. Sublimation enthalpies were derived from thermogravimetric experiments, measuring the rate of mass loss and using Langmuir and Clausius-Clapeyron equations. Fusion enthalpies and heat capacities of the solid and liquid phases were measured as functions of temperature by differential scanning calorimetry, and the heat capacities of the gas phase were calculated via molecular orbital calculations. Theoretical and experimental ΔfHm°(g)'s differed by <5.5kJ·mol-1, and isomerization enthalpies are discussed. In addition, using theoretical tools [natural bond orbitals (NBO) and quantum theory of atoms in molecules (QTAIM)], intramolecular interactions were analyzed. An uncommon hypervalent four-center six-electron interaction of type O···S-S···O was found in 2DNDPDS. This hypervalent interaction, in addition to the extent of conjugation between the aryl and NO2 moieties and the formation of intramolecular C-H···S hydrogen bonds, counteracts the repulsion caused by steric repulsions. Hydrogen bonding was confirmed through geometric parameters as well as QTAIM.

Electronic Structure Effects Related to the Origin of the Remarkable Near-Infrared Absorption of Blastochloris viridis' Light Harvesting 1-Reaction Center Complex.

Various photosynthetic organisms have evolved to absorb light in different regions of the visible light spectrum, thus adapting to the various lighting conditions available on Earth. While most of these autotrophic organisms absorb wavelengths around the 700-800 nm region, some are capable of red-shifted absorptions above this range, but none as remarkably as Blastochloris viridis whose main absorption is observed at 1015 nm, approximately 220 nm (0.34 eV) lower in energy than their main constituent pigments, BChl-b, whose main absorption is observed at 795 nm. The structure of its light harvesting 1-reaction center was recently elucidated by cryo-EM; however, the electronic structure details behind this red-shifted absorption remain unattended. We used hybrid quantum mechanics/molecular mechanics (QM/MM) calculations to optimize one of the active centers and performed classical molecular dynamics (MD) simulations to sample conformations beyond the optimized structure. We did excited state calculations with the time-dependent density functional theory method at the CAM-B3LYP/cc-pVDZ level of theory. We reproduced the near IR absorption by sequentially modifying the number of components involved in our systems using representative structures from the calculated MD ensemble. Natural transition orbital analysis reveals the participation of the BChl-b fragments to the main transition in the native structure and the structures obtained from the QM/MM and MD simulations. H-bonding pigment-protein interactions play a role on the conformation stabilization and orientation; however, the bacteriochlorin ring conformations and the exciton delocalization are the most relevant factors to explain the red-shifting phenomenon.

Accelerated Dimerization of α,ß-Unsaturated D-Xylo-Hexofurano-5-ulose Derivatives through Asynchronous Hetero-Diels-Alder Reaction.

While some hetero-Diels-Alder (HDA) reactions are accelerated by either carbonyl or phosphate groups attached directly to the heterodiene moiety, the alkyl or aryl groups, on the other hand, have minimal influence. However, in this article, we demonstrate that aryl groups have a significant effect on the spontaneous dimerization reaction of α,ß-unsaturated D-xylo-hexofurano-5-ulose derivatives to their respective pyrano adducts via intermolecular HDA reaction. Experimental and computational studies provide strong evidence that dimerization follows the Woodward-Katz two-stage mechanism reaction (asynchronous process), from which the aryl/aryl π-stacking interaction is mainly responsible for the rate-determining step (RDS) and electrostatic interaction for the second bond formation. Since the latter interaction is highly affected by dipolar moment, 5-ulose derivative having a strong electron-withdrawing group (R = CN; µ = 14.3 D) is spontaneously dimerized more than 15 times faster than 5-ulose that possesses an electron-donating group (R = OMe; µ = 2.1 D).

Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations: The Isoelectric Points of Amino Acids as a Case Study.

Theoretical calculation of equilibrium dissociation constants is a very computationally demanding and time-consuming process since it requires an extremely accurate computation of the solvation free energy changes for each of the species involved. By correlating the minimum surface electrostatic potential (VS,min) on the nitrogen atom of several aliphatic amino groups-calculated at the density functional theory (DFT) ωB97X-D/cc-pVDZ level of theory-we obtained regression models for each kind of substitution pattern from which we interpolate their corresponding pKb values with remarkable accuracy: primary R2 = 0.9519; secondary R2 = 0.9112; and tertiary R2 = 0.8172 (N = 20 for each family). These models were validated with tests sets (N = 5) with mean absolute error (MAE) values of 0.1213 (primary), 0.4407 (secondary), and 0.3057 (tertiary). Combining this ansatz with another previously reported by our group to estimate pKa values [Caballero-García, G.; et al. Molecules 2019, 24(1), 79] we are able to reproduce the isoelectric points of 13 amino acids with no titrable side chains with MAE = 0.4636 pI units.

Porphyrin Supramolecular Arrays Formed by Weakly Interacting Meso-Functional Groups on Au(111).

The formation of a binary porphyrinic self-assembled system between meso-tetrakis(4-carboxyphenyl) porphyrin (TCPP) and meso-tetrakis(4-dimethyl amino) porphyrin (TDAP) was easily designed through non-covalent interactions in solution and adsorbed on a gold substrate. It was found that non-covalent interactions and geometrical conformations between porphyrins allow their self-assembly into a well-defined arrangement, which was confirmed by UV-Vis spectroscopy, electrochemistry, atomic force microscopy and density functional theory (DFT) studies.

Transition-Metal-Free Deconstructive Lactamization of Piperidines.

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp3 )-C(sp3 ) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3-alkoxyamino-2-piperidones, which were prepared from piperidines through a dual C(sp3 )-H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3-alkoxyamino-2-piperidones to 3-keto-2-piperidones, followed by a regioselective Baeyer-Villiger oxidation to give N-carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.

Can an n(O) → π* Interaction Provide Thermodynamic Stability to Naturally Occurring Cephalosporolides?

The stereocontrolled synthesis of naturally occurring products containing a 5,5-spiroketal molecular structure represents a major synthetic problem. Moreover, in a previous work, the stereocontrolled synthesis of cephalosporolide E (ceph E), which presumably was obtained from its epimer congener (ceph F) through an acid-mediated equilibration process, was reported. Consequently, we performed a theoretical investigation to provide relevant information regarding the title question, and it was found that the higher thermodynamic stability of ceph E, relative to ceph F, is caused by an n → π* interaction between a lone electron pair of the oxygen atom of the spiroketal ring (nO) and the antibonding orbital of the carbonyl group (π*C=O). Although similar stereoelectronic interactions have been disclosed in other molecular structures, its presence in ceph E, and very likely in other related naturally occurring products, represents a novel nonanomeric stabilizing effect that should be introduced into the chemical literature.

Calculation of VS,max and Its Use as a Descriptor for the Theoretical Calculation of pKa Values for Carboxylic Acids.

The theoretical calculation of pKa values for Brønsted acids is a challenging task that involves sophisticated and time-consuming methods. Therefore, heuristic approaches are efficient and appealing methodologies to approximate these values. Herein, we used the maximum surface electrostatic potential (VS,max) on the acidic hydrogen atoms of carboxylic acids to describe the H-bond interaction with water (the same descriptor that is used to characterize σ-bonded complexes) and correlate the results with experimental pKa values to obtain a predictive model for other carboxylic acids. We benchmarked six different methods, all including an implicit solvation model (water): Five density functionals and the Møller⁻Plesset second order perturbation theory in combination with six different basis sets for a total of thirty-six levels of theory. The ωB97X-D/cc-pVDZ level of theory stood out as the best one for consistently reproducing the reported pKa values, with a predictive power of 98% correlation in a test set of ten other carboxylic acids.

The Intramolecular Hydrogen Bond N-H···S in 2,2'-Diaminodiphenyl Disulfide: Experimental and Computational Thermochemistry.

The intramolecular hydrogen bond of the N-H···S type has been investigated sparingly by thermochemical and computational methods. In order to study this interaction, the standard molar enthalpies of formation in gaseous phase of diphenyl disulfide, 2,2'-diaminodiphenyl disulfide and 4,4'-diaminodiphenyl disulfide at T = 298.15 K were determined by experimental thermochemical methods and computational calculations. The experimental enthalpies of formation in gas-phase were obtained from enthalpies of formation in crystalline phase and enthalpies of sublimation. Enthalpies of formation in crystalline phase were obtained using rotatory bomb combustion calorimetry. By thermogravimetry, enthalpies of vaporization were obtained, and by combining them with enthalpies of fusion, the enthalpies of sublimation were calculated. The Gaussian-4 procedure and the atomization method were applied to obtain enthalpies of formation in gas-phase of the compounds under study. Theoretical and experimental values are in good agreement. Through natural bond orbital (NBO) analysis and a topological analysis of the electronic density, the intramolecular hydrogen bridge (N-H···S) in the 2,2'-diaminodiphenyl disulfide was confirmed. Finally, an enthalpic difference of 11.8 kJ·mol-1 between the 2,2'-diaminodiphenyl disulfide and 4,4'-diaminodiphenyl disulfide was found, which is attributed to the intramolecular N-H···S interaction.

Looking Inside the Intramolecular C-H∙∙∙O Hydrogen Bond in Lactams Derived from α-Methylbenzylamine.

Recently, strong evidence that supports the presence of an intramolecular C-H···O hydrogen bond in amides derived from the chiral auxiliary α-methylbenzylamine was disclosed. Due to the high importance of this chiral auxiliary in asymmetric synthesis, the inadvertent presence of this C-H···O interaction may lead to new interpretations upon stereochemical models in which this chiral auxiliary is present. Therefore, a series of lactams containing the chiral auxiliary α-methylbenzylamine (from three to eight-membered ring) were theoretically studied at the MP2/cc-pVDZ level of theory with the purpose of studying the origin and nature of the C-Hα···O interaction. NBO analysis revealed that rehybridization at C atom of the C-Hα bond (s-character at C is ~23%) and the subsequent bond polarization are the dominant effect over the orbital interaction energy n(O)→σ*C-Hα (E(2) < 2 kcal/mol), causing an important shortening of the C-Hα bond distance and an increment in the positive charge in the Hα atom.

The Stabilizing Role of the Intramolecular C-H···O Hydrogen Bond in Cyclic Amides Derived From α-Methylbenzylamine.

A series of five-, six-, seven-, and eight-membered lactams containing the chiral auxiliary α-methylbenzylamine were structurally analyzed and further studied by DFT calculations with the purpose to examine with detail the previously detected intramolecular C-H···O hydrogen-bonding interaction formed between the hydrogen atom of the α-methylbenzylamine and the carbonyl group of the cyclic amide. The main objective was to establish whether its presence does have a tangible relevance in their spatial arrangement in solution and in the solid state or is a simple and not stabilizing interaction.

ß-Oxygen effect in the Barton-McCombie deoxygenation reaction: further experimental and theoretical findings.

The chemistry of (S)-methyl xanthates derived from xylo- and ribo-furanose derivatives in the presence of the stannyl radical is investigated. Xanthate derived from ß-xylo-furanose affords exclusively a deoxygenated product; whereas, under the same reaction conditions, the α-ribo-furanose xanthate derivative produces quantitatively a hemithioacetal compound. We reasoned that in the case of the ß-xylo-furanose derivative, a favorable ß-oxygen effect in the Barton-McCombie deoxygenation reaction is operating where, according to theoretical calculations, unusual molecular orbital interactions (and not strain, as previously proposed) are present. These orbital interactions involve the SOMO (intermediary generated from the stannyl radical addition) with the σ* orbital of the bond undergoing cleavage and this with the two C-O antibonding orbitals anti oriented. Such molecular orbital interactions are not present in the α-ribo-furanose; therefore, the ß-scission is highly delayed, and due to the reversibly nature of the stannyl radical addition, the ribo-furanose xanthate is forced to take an alternative route: the homolytic substitution (S(H)2) of the sulfide sulfur by stannyl radical. This radical addition gives the alkoxythiocarbonyl radical, which is trapped by Bu3SnH before the elimination of carbonyl sulfide; subsequently, radical stannyl addition followed by radical reduction produces the hemithioacetal.