Damian G. Allis

Molybdophosphonate clusters as building blocks in the oxomolybdate-organodiphosphonate/cobalt(II)-organoimine system: structural influences of secondary metal coordination preferences and diphosphonate tether lengths.

Hydrothermal conditions have been used in the preparation of a series of organic-inorganic hybrid materials of the cobalt-molybdophosphonate family. The reactions of MoO(3), cobalt(II) acetate or cobalt(II) acetylacetonate, tetra-2-pyridylpyrazine (tpyprz), and organodiphosphonic acids H(2)O(3)P(CH(2))nPO(3)H(2) (n = 1-5 and 9) of varying tether lengths yielded compounds of the general type {Co(2)(tpyprz)(H(2)O)(m)}4+/MoxOy{O(3)P(CH(2))(n)PO(3)}z. The recurring theme of the structural chemistry is the incorporation of {Mo(5)O(15)(O(3)PR)(2)}(4-) clusters as molecular building blocks observed in the structures of nine phases (compounds 2-9 and 11). The structural consequences of variations in reaction conditions are most apparent in the series with propylene diphosphonate, where four unique structures 4-7 are observed, including two distinct three-dimensional architectures for compounds 5 and 6 whose formulations differ only in the number of water molecules of crystallization. With pentyldiphosphonate, a second phase 10 is obtained which exhibits a unique cluster building block, the hexamolybdate [Mo(6)O(18){O(3)P(CH(2))(5)PO(3)}](4-). In the case of methylenediphosphonic acid, a third structural motif, the trinuclear {(Mo(3)O(8))(O(3)PCH(2)PO(3))}2- subunit, is observed in compound 1. The structural chemistry of compounds 1-11 of this study is quite distinct from that of the {Ni(2)(tpyprz)(H(2)O)(m)}(4+)/Mo(x)O(y){O(3)P(CH(2))(n)PO(3)}z family, as well as that of the copper-based family. The structural diversity of this general class of materials reflects the coordination preferences of the M(II) sites, the extent of aqua ligation to the M(II) sites, the participation of both phosphate oxygen atoms and molybdate oxo-groups in linking to the M(II) sites, and the variability in the number of attachment sites at the molybdophosphonate clusters. Since the charge densities at the peripheral oxygen atoms of the clusters are quite uniform, the attachment of {M(2)(tpyprz)}(4+) subunits to the molybdophosphonates appears to be largely determined by steric, coulombic, and packing factors, as shown by extensive density functional theory calculations.

Synthesis and stabilization—advances in organoalkaline earth metal chemistry

The last decade has seen an impressive growth in alkaline earth metal chemistry, with applications ranging from synthetic organic and polymer chemistry to materials science. As a consequence, alkaline earth metal chemistry has made a leap from obscurity into the spotlight of modern organometallic chemistry. Much of this rapid development was made possible by the establishment of novel synthetic procedures that allowed facile access to the target compounds, as many conventional synthetic routes posed and continue to pose significant limitations. Novel approaches have allowed the preparation of a multitude of compounds, initiating progress not thought possible just five years ago. Examination of the new compounds delineates several factors responsible for their structure and function. Key elements in the coordination, aggregation behavior, and reactivity of these systems have been linked to secondary interactions, including M-Cpi, M-Npi, M-F, and M-H(agostic) interactions. This feature article will provide a very brief overview of established synthetic procedures, including a brief discussion on specific shortcomings. This will be followed by a detailed presentation of novel methodologies that are the core of the rapid development of alkaline earth metal chemistry. The second part of the article will be concerned with the analysis of various secondary interactions and their role in the further development of this rapidly emerging field of chemistry.

Vitamin B12 in drug delivery: breaking through the barriers to a B12 bioconjugate pharmaceutical

Importance of the field: Vitamin B12 (B12) is a rare and vital micronutrient for which mammals have developed a complex and highly efficient dietary uptake system. This uptake pathway consists of a series of proteins and receptors, and has been utilized to deliver several bioactive and/or imaging molecules from 99mTc to insulin. Areas covered in this review: The current field of B12-based drug delivery is reviewed, including recent highlights surrounding the very pathway itself. What the reader will gain: Despite over 30 years of work, no B12-based drug delivery conjugate has reached the market-place, hampered by issues such as limited uptake capacity, gastrointestinal degradation of the conjugate or high background uptake by healthy tissues. Variability in dose response among individuals, especially across ageing populations and slow oral uptake (several hours), has also slowed development and interest. Take home message: This review is intended to stress again the great potential, as yet not fully realized, for B12-based therapeutics, tumor imaging and oral drug delivery. This review discusses recent reports that demonstrate that the issues noted above can be overcome and need not be seen as negating the great potential of B12 in the drug delivery field.

Cryogenic Terahertz Spectrum of (+)-Methamphetamine Hydrochloride and Assignment Using Solid-State Density Functional Theory

The cryogenic terahertz spectrum of (+)-methamphetamine hydrochloride from 10.0 to 100.0 cm(-1) is presented, as is the complete structural analysis and vibrational assignment of the compound using solid-state density functional theory. This cryogenic investigation reveals multiple spectral features that were not previously reported in room-temperature terahertz studies of the title compound. Modeling of the compound employed eight density functionals utilizing both solid-state and isolated-molecule methods. The results clearly indicate the necessity of solid-state simulations for the accurate assignment of solid-state THz spectra. Assignment of the observed spectral features to specific atomic motions is based on the BP density functional, which provided the best-fit solid-state simulation of the experimental spectrum. The seven experimental spectral features are the result of thirteen infrared-active vibrational modes predicted at a BP/DNP level of theory with more than 90% of the total spectral intensity associated with external crystal vibrations.

Polyhedral-based nonlinear optical materials. Part 1. Theoretical investigation of some new high nonlinear optical response compounds involving carboranes and charged aromatic donors and acceptors

A calculational investigation using semiempirical methods of the molecular and electronic structures, along with the nonlinear optical responses, of a series of compounds in which icosahedral carborane polyhedra bridge charged aromatic donor and acceptor moieties, specifically tropyl (C7H7 ) and cyclopentadienyl (C5H5 ) groups, found that these molecules show exceptionally large calculated second-order responses. These compounds were found to give calculated first hyperpolarizabilities (b) ranging from 8.6 to 1226.010 30 cm 5 esu 1 at 0.5 eV excitation energy. These nonlinear optical responses are understood within the framework of the two-state model using molecular orbital and electronic structure considerations.

Investigation of (1R,2S)‐(−)‐Ephedrine by Cryogenic Terahertz Spectroscopy and Solid‐State Density Functional Theory

The terahertz (THz) spectrum of the pharmaceutical (1R,2S)-(-)-ephedrine from 8.0 to 100.0 cm(-1) is investigated at liquid-nitrogen (78.4 K) temperature. The spectrum exhibits several distinct features in this range that are characteristic of the crystal form of the compound. A complete structural analysis and vibrational assignment of the experimental spectrum is performed using solid-state density functional theory (DFT) and cryogenic single-crystal X-ray diffraction. Theoretical modeling of the compound includes an array of density functionals and basis sets with the final assignment of the THz spectrum performed at a PW91/6-311G(d,p) level of theory, which provides excellent solid-state simulation agreement with experiment. The solid-state analysis indicates that the seven experimental spectral features observed at low temperature consist of 13 IR-active vibrational modes. Of these modes, nine are external crystal vibrations and provide approximately 57% of the predicted spectral intensity. This study demonstrates that the THz spectra of complex pharmaceuticals may be well reproduced by solid-state DFT calculations and that inclusion of the crystalline environment is necessary for realistic and accurate simulations.

Exploring the Implications of Vitamin B12 Conjugation to Insulin on Insulin Receptor Binding

The dynamic behavior of insulin in solution and its binding geometry with the insulin receptor (IR) have been the focus of experimental and computational studies. We investigated how the structure of an orally deliverable insulin changes in solution after vitamin B12 conjugation and its effect on IR binding capacity. In vitro immunoelectron microscopy confirms conjugate activity, IR binding, and cellular uptake.

Examination of Phencyclidine Hydrochloride via Cryogenic Terahertz Spectroscopy, Solid-State Density Functional Theory, and X-ray Diffraction

The terahertz (THz) spectrum of phencyclidine hydrochloride from 7.0 to 100.0 cm(-1) has been measured at cryogenic (78.4 K) temperature. The complete structural analysis and vibrational assignment of the compound have been performed employing solid-state density functional theory utilizing eight generalized gradient approximation density functionals and both solid-state and isolated-molecule methods. The structural results and the simulated spectra display the substantial improvement obtained by using solid-state simulations to accurately assign and interpret solid-state THz spectra. A complete assignment of the spectral features in the measured THz spectrum has been completed at a VWN-BP/DNP level of theory, with the VWN-BP density functional providing the best-fit solid-state simulation of the experimentally observed spectrum. The cryogenic THz spectrum contains eight spectral features that, at the VWN-BP/DNP level, consist of 15 infrared-active vibrational modes. Of the calculated modes, external crystal vibrations are predicted to account for 42% of the total spectral intensity.

Experimental and theoretical studies of tetramethoxy-p-benzoquinone: infrared spectra, structural and lithium insertion properties

In the search for low-polluting electrode materials for batteries, the use of redox-active organic compounds represents a promising alternative to conventional metal-based systems. In this article we report a combined experimental and theoretical study of tetramethoxy-p-benzoquinone (TMQ). In carbonate-based electrolytes, electrochemical behaviour of this compound is characterized by a reversible insertion process located at approximately 2.85 V vs. Li+/Li0. This relatively high potential reactivity, coupled with our effort to develop computational methodologies in the field of organic electrode materials, prompted us to complement these experimental data with theoretical studies performed using density functional theory (DFT). Single crystals of TMQ were synthesized and thoroughly characterized showing that this quinonic species crystallised in the P21/n space group. The experimental crystal structure of TMQ was then used to assess various DFT methods. The structural features and vibrational spectra were thus predicted by using as a whole five common density functionals (PBE, LDA, revPBE, PBEsol, B3PW91) with and without a semi-empirical correction to account for the van der Waals interactions using either Grimmes (DFT-D2) or Tkatchenko–Scheffler (TS) scheme. The most reliable combination of the DFT functional and the explicit dispersion correction was chosen to study the Li-intercalated molecular crystal (LiTMQ) with the view of indentifying Li insertion sites. A very close agreement with the experiment was found for the average voltage by using the most stable relaxed hypothetical LiTMQ structure. Additionally, a comparison of vibrational spectra gained either for TMQ molecule and its dimer in gas phase or through periodic calculation was undertaken with respect to the experimentally measured infrared spectra. The topological features of the bonds were also investigated in conjunction with estimates of net atomic charges to gain insight into the effect of chemical bonding and intermolecular interaction on Li intercalation. Finally, π-electron delocalization of both quinone and alkali salts of p-semiquinone were determined using the Harmonic Oscillator model of Aromaticity (HOMA) or aromatic fluctuation index (FLU) calculations.

Density Functional Dependence in the Theoretical Analysis of the Terahertz Spectrum of the Illicit Drug MDMA (Ecstasy)

In this paper, the experimental terahertz (THz) spectrum of the illicit drug 3, 4-methylenedioxymethamphetamine hydrochloride (MDMA.HCl, C11H16O2N+·Cl-) has been rigorously modeled using solid-state density functional theory (DFT). The compound MDMA.HCl is more widely known by the street name ¿Ecstasy¿ and is a commonly abused drug. The first-principles simulation and assignment of the experimental THz absorption features is a key step in the validation of the spectrum for use in spectral databases for illicit compound sensing. This theoretical study includes the use of an array of generalized gradient approximation density functionals in order to provide a thorough understanding of the performance of the various functionals in the simulation of this crystalline drug. Of the seven studied functionals, the BP functional yielded superior agreement with the experimental data in terms of intramolecular structure, and in the position and intensity of spectral features.