Synthesis of 1,2-Disubstituted Adamantane Derivatives by Construction of the Adamantane Framework.

This review summarizes achievements in the synthesis of 1,2-disubstituted adamantane derivatives by the construction of the tricyclic framework either by total synthesis or by ring expansion/contraction reactions of corresponding adamantane homologues. It is intended to complement reviews focusing on the preparation of 1,2-disubstituted derivatives by C-H functionalization methods.

The fate and behavior of petroleum biomarkers in diluted bitumen and conventional crude oil exposed to natural sunlight in simulated seawater.

Given that the physicochemical properties of diluted bitumen (dilbit) can differ from those of conventional crude oil, understanding the fate and behavior of this petroleum product in the environment becomes vital. This study involves the analysis of the photolytic behavior of some representative petroleum biomarkers, bicyclic sesquiterpanes (BSs), admantanes (ADs), diamantanes (DAs), and mono- and triaromatic steranes (MASs and TASs), by exposing Cold Lake Blend (CLB) and Alberta Sweet Mixed Blend (MSW) to winter and summer insolation after being spilled onto artificial brines. Aromatic steranes in all control samples remained relatively stable, whereas the biomarkers of BSs, ADs, and DAs were less stable. Similar to the exhaustive loss of the C10-C17 alkanes, 91%-99% of BSs, ADs, and DAs were lost after five days of insolation, especially in summer. Both MASs and TASs were lost gradually in most scenarios, although both of them were lost faster in MSW than observed for CLB. The removal of MASs and TASs did not differ significantly from each other, although their loss was less than observed for PAHs having similar number of rings and greater than for the C21-C33n-alkanes. Therefore, photooxidation, not evaporation or biodegradation, was the main factor responsible for oxidizing these aromatic steranes. However, biomarkers of BSs, ADs and DAs were mostly lost through evaporation. Therefore, aromatic steranes have the potential to be utilized to evaluate the photolytic behavior of petroleum hydrocarbons, while BSs, ADs, and DAs should not be used for this purpose.

Preparation and characterization of non-aromatic ether self-assemblies on a HOPG surface.

On-surface self-assemblies of aromatic organic molecules have been widely investigated, but the characterization of analogous self-assemblies consisting of fully sp3-hybridized molecules remains challenging. The possible on-surface orientations of alkyl molecules not exclusively comprised of long alkyl chains are difficult to distinguish because of their inherently low symmetry and non-planar nature. Here, we present a detailed study of diamondoid ethers, structurally rigid and fully saturated molecules, which form uniform 2D monolayers on a highly oriented pyrolytic graphite (HOPG) surface. Using scanning tunneling microscopy, various computational tools, and x-ray structural analysis, we identified the most favorable on-surface orientations of these rigid ethers and accounted for the forces driving the self-organization process. The influence of the oxygen atom and London dispersion interactions were found to be responsible for the formation of the observed highly ordered 2D ether assemblies. Our findings provide insight into the on-surface properties and behavior of non-aromatic organic compounds and broaden our understanding of the phenomena characteristic of monolayers consisting of non-planar molecules.

Opening of the Diamondoid Cage upon Ionization Probed by Infrared Spectra of the Amantadine Cation Solvated by Ar, N2 , and H2 O.

Radical cations of diamondoids, a fundamental class of very stable cyclic hydrocarbon molecules, play an important role in their functionalization reactions and the chemistry of the interstellar medium. Herein, we characterize the structure, energy, and intermolecular interaction of clusters of the amantadine radical cation (Ama+ , 1-aminoadamantane) with solvent molecules of different interaction strength by infrared photodissociation (IRPD) spectroscopy of mass-selected Ama+ Ln clusters, with L=Ar (n≤3) and L=N2 and H2 O (n=1), and dispersion-corrected density functional theory calculations (B3LYP-D3/cc-pVTZ). Three isomers of Ama+ generated by electron ionization are identified by the vibrational properties of their rather different NH2 groups. The ligands bind preferentially to the acidic NH2 protons, and the strength of the NH…L ionic H-bonds are probed by the solvation-induced red-shifts in the NH stretch modes. The three Ama+ isomers include the most abundant canonical cage isomer (I) produced by vertical ionization, which is separated by appreciable barriers from two bicyclic distonic iminium ions obtained from cage-opening (primary radical II) and subsequent 1,2 H-shift (tertiary radical III), the latter of which is the global minimum on the Ama+ potential energy surface. The effect of solvation on the energetics of the potential energy profile revealed by the calculations is consistent with the observed relative abundance of the three isomers. Comparison to the adamantane cation indicates that substitution of H by the electron-donating NH2 group substantially lowers the barriers for the isomerization reaction.

The Role of Packing, Dispersion, Electrostatics, and Solvation in High-Affinity Complexes of Cucurbit[n]urils with Uncharged Polar Guests.

The rationalization of non-covalent binding trends is both of fundamental interest and provides new design concepts for biomimetic molecular systems. Cucurbit[n]urils (CBn) are known for a long time as the strongest synthetic binders for a wide range of (bio)organic compounds in water. However, their host-guest binding mechanism remains ambiguous despite their symmetric and simple macrocyclic structure and the wealth of literature reports. We herein report experimental thermodynamic binding parameters (ΔG, ΔH, TΔS) for CB7 and CB8 with a set of hydroxylated adamantanes, di-, and triamantanes as uncharged, rigid, and spherical/ellipsoidal guests. Binding geometries and binding energy decomposition were obtained from high-level theory computations. This study reveals that neither London dispersion interactions, nor electronic energies or entropic factors are decisive, selectivity-controlling factors for CBn complexes. In contrast, peculiar host-related solvation effects were identified as the major factor for rationalizing the unique behavior and record-affinity characteristics of cucurbit[n]urils.

Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents.

Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical, chemical, optical and biological properties, making them significant active moiety carriers for biomedical application. These are known as the most 'captivating' crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era. Alongside, it becomes increasingly important to find, ascertain and circumvent the negative aspects associated with nanodiamonds. Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry. To take advantage of nanodiamond potential in drug delivery, focus has to be laid on its purity, surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment. This review emphasizes on the basic properties, synthesis techniques, surface modification techniques, toxicity issues and biomedical applications of nanodiamonds. For the development of nanodiamonds as an effective dosage form, researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces.

Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents / 药物分析学报

Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical, chemical, optical and biological properties, making them significant active moiety carriers for biomedical application. These are known as the most'captivating' crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era. Alongside, it becomes increasingly important to find, ascertain and circumvent the negative aspects associated with nano-diamonds. Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry. To take advantage of nanodiamond potential in drug delivery, focus has to be laid on its purity, surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment. This review emphasizes on the basic properties, synthesis techniques, surface modification techniques, toxicity issues and biomedical applications of nanodiamonds. For the devel-opment of nanodiamonds as an effective dosage form, researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces.

A green approach for the extraction of diamondoids from petroleum source rock.

Extraction of adamantanes and diamantanes from petroleum source rock using nonionic surfactant was investigated and the optimum conditions for yields of the diamondoids were determined. The conventionally used accelerated solvent extraction method was compared to an innovative microwave-assisted nonionic surfactant extraction (MANSE). A three-level full factorial design of experiment (DoE) was adopted for the optimization of MANSE, involving solvent concentration, extraction temperature as well as extraction time. In-tube extraction (ITEX-2) using TENAX TA as sorbent in combination with gas chromatography-mass spectrometry (GC-MS) was used to determine the diamondoids in the extract. The results revealed that solvent concentration, extraction temperature and time have significant effects on extraction yields of the diamondoids. 0.04 M was the optimum surfactant concentration for extraction of both, adamantane and diamantane. The highest yields of the diamondoids were obtained at extraction temperature of 80 °C. The optimum extraction time for both adamantane and diamantane was 10 min. In comparison with the accelerated solvent extraction method, the results showed that MANSE is more efficient. This study has revealed that MANSE is a robust and efficient environmentally benign sample preparation method for geochemical evaluation of petroleum source rock.

In silico Complexes of Amino Acids and Diamondoids.

We report on the specific interaction of a small diamond-like molecule, known as diamondoid, with single amino-acids forming nano/bio molecular complexes. Using time-dependent density-functional theory calculations we have studied two different relative configurations of three prototypical amino acids, phenylalanine, tyrosine, and tryptophan, with the diamondoid. The optical and charge-transfer properties of these complexes exhibit amino acid and topology specific features which can be directly utilized for in the direction of novel biomolecule detection schemes.

Diamondoid Amino Acid-Based Peptide Kinase†A Inhibitor Analogues.

The incorporation of diamondoid amino acids (DAAs) into peptide-like drugs is a general strategy to improve lipophilicity, membrane permeability, and metabolic stability of peptidomimetic pharmaceuticals. We designed and synthesized five novel peptidic DAA-containing kinase inhibitors of protein kinase A using a sophisticated molecular dynamics protocol and solid-phase peptide synthesis. By means of a thermophoresis binding assay, NMR, and crystal structure analysis, we determined the influence of the DAAs on the secondary structure and binding affinity in comparison to the native protein kinase inhibitor, which is purely composed of proteinogenic amino acids. Affinity and binding pose are largely conserved. One variant showed 6.5-fold potency improvement, most likely related to its increased side chain lipophilicity. A second variant exhibited slightly decreased affinity presumably due to loss of hydrogen-bond contacts to surrounding water molecules of the first solvation shell.

London Dispersion Directs On-Surface Self-Assembly of [121]Tetramantane Molecules.

London dispersion (LD) acts between all atoms and molecules in nature, but the role of LD interactions in the self-assembly of molecular layers is still poorly understood. In this study, direct visualization of single molecules using atomic force microscopy with CO-functionalized tips revealed the exact adsorption structures of bulky and highly polarizable [121]tetramantane molecules on Au(111) and Cu(111) surfaces. We determined the absolute molecular orientations of the completely sp3-hybridized tetramantanes on metal surfaces. Moreover, we demonstrate how LD drives this on-surface self-assembly of [121]tetramantane hydrocarbons, resulting in the formation of a highly ordered 2D lattice. Our experimental findings were underpinned by a systematic computational study, which allowed us to quantify the energies associated with LD interactions and to analyze intermolecular close contacts and attractions in detail.

Type-dependent identification of DNA nucleobases by using diamondoids.

The possibility of distinguishing between DNA nucleobases of different sizes is manifested here through quantum-mechanical simulations. By using derivatives of small, modified diamond clusters, known as diamondoids, it is possible to separate the pyrimidines (cytosine and thymine) from the larger purines (adenine and guanine), according to the collective electronic and binding properties of these DNA nucleobases and the diamondoid. The latter acts as a probe with which these properties can be examined in detail. Short single-stranded DNA is built up from single nucleobases to reveal the effect of each DNA unit on the sensing abilities of the diamondoid probe. Several ways of orienting the nucleobases, nucleosides, nucleotides, and short single-stranded DNA are investigated; these lead to quite different electronic properties and may or may not enhance the possibility of separating the DNA nucleobases. For the optimum orientation, that is, one that promotes stronger hydrogen bonding of the diamondoid to the short DNA strand, it is found that the electronic band gaps of a purine strand lie in a completely different range to the band gaps of a pyrimidine strand. This difference can be over 1 eV, which is measurable and shows the potential of using diamondoids and their derivatives in biosensing devices.

Self-assembly of diamondoid molecules and derivatives (MD simulations and DFT calculations).

We report self-assembly and phase transition behavior of lower diamondoid molecules and their primary derivatives using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. Two lower diamondoids (adamantane and diamantane), three adamantane derivatives (amantadine, memantine and rimantadine) and two artificial molecules (ADM·Na and DIM·Na) are studied separately in 125-molecule simulation systems. We performed DFT calculations to optimize their molecular geometries and obtained atomic electronic charges for the corresponding MD simulation, by which we predicted self-assembly structures and simulation trajectories for the seven different diamondoids and derivatives. Our radial distribution function and structure factor studies showed clear phase transitions and self-assemblies for the seven diamondoids and derivatives.