An Osteoconductive Antibiotic Bone Eluting Putty with a Custom Polymer Matrix.

With the rising tide of antibiotic resistant bacteria, extending the longevity of the current antibiotic arsenal is becoming a necessity. Developing local, controlled release antibiotic strategies, particularly for difficult to penetrate tissues such as bone, may prove to be a better alternative. Previous efforts to develop an osteoconductive local antibiotic release device for bone were created as solid molded composites; however, intimate contact with host bone was found to be critical to support host bone regrowth; thus, an osteocondconductive antibiotic releasing bone void filling putty was developed. Furthermore, a controlled releasing polymer matrix was refined using pendant-functionalized diols to provide tailorable pharmacokinetics. In vitro pharmacokinetic and bioactivity profiles were compared for a putty formulation with an analogous composition as its molded counterpart as well as four new pendant-functionalized polymers. A best-fit analysis of polymer composition in either small cylindrical disks or larger spheres revealed that the new pendant-functionalized polymers appear to release vancomycin via both diffusion and erosion regardless of the geometry of the putty. In silico simulations, a valuable technique for diffusion mediated controlled release models, will be used to confirm and optimize this property.

Relaxation and dissociation following photoexcitation of the (µ-N2)[Mo(N[t-Bu]Ar)3]2 dinitrogen cleavage intermediate.

Frequency resolved pump-probe spectroscopy was performed on isolated (µ-N(2))[Mo(N[t-Bu]Ar)(3)](2) (Ar = 3,5-C(6)H(3)Me(2)), an intermediate formed in the reaction of Mo(N[t-Bu]Ar)(3) to bind and cleave dinitrogen. Evidence is presented for 300 fs internal conversion followed by subpicosecond vibrational cooling on the ground electronic state in competition with bond dissociation. Fast cooling following photoexcitation leads to a relatively low overall dissociation yield of 5%, in quantitative agreement with previous work [Curley, J. J.; Cooke, T. R.; Reece, S. Y.; Mueller, P.; Cummins, C. C. J. Am. Chem. Soc. 2008, 130, 9394]. Coupling of vibrational modes to the excitation and internal conversion results in a nonthermal distribution of energy following conversion, and this provides sufficient bias to allow the nitrogen cleavage reaction to compete with breaking of the Mo-NN bond despite a higher energetic barrier on the ground state.

Preparation and physical properties of early-late heterobimetallic compounds featuring Ir-M bonds (M = Ti, Zr, Hf).

Treatment of Cp*Ir N(t)Bu (1) with the appropriate metallocene equivalent is an effective route for the preparation of the heterobimetallic complexes Cp*Ir(µ-N(t)Bu)MCp(2) (2-M, M = Ti, Zr, Hf). The electronic structures of the isostructural series of compounds, 2-M, are described with reference to single-crystal X-ray, Raman, UV-vis, and cyclic voltammetry data. Density functional theory (DFT) calculations were used to aid in the interpretation of this experimental work. Treatment of the zirconium or hafnium congeners with 2,6-lutidinium triflate leads to protonation of the Ir-M bond, to afford Cp*Ir(µ-N(t)Bu)(µ-H)MCp(2)OTf (3-M, M = Zr, Hf). Compound 3-Zr was characterized by single-crystal X-ray diffraction and independently prepared by the reaction of 1 and Cp(2)Zr(H)Cl in the presence of Me(3)SiOTf. In reactions analogous to those for 2-Zr, 2-Hf reacts with S(8) and aryl azides to insert an S-atom or aryl azide fragment into the metal-metal bond, yielding Cp*Ir(µ-N(t)Bu)(µ-S)HfCp(2) (6-Hf) and Cp*Ir(µ-N(t)Bu)(N(3)Ph)HfCp(2) (4-Hf), respectively. Heating 4-Hf results in N(2) extrusion to form Cp*Ir(µ-N(t)Bu)(NPh)HfCp(2) (5-Hf). The kinetics of the latter reaction were studied to obtain activation parameters and a Hammett trend; these data are compared to those for the analogous reaction involving Ir-Zr heterobimetallics.

Nitrogen fixation to cyanide at a molybdenum center.

Facile methoxymethylation of N(2)-derived nitride NMo(N[(t)Bu]Ar)(3) provided the imido cation [MeOCH(2)NMo(N[(t)Bu]Ar)(3)](+) as its triflate salt in 88% yield. Treatment of the latter with LiN(SiMe(3))(2) provided blue methoxyketimide complex MeO(H)CNMo(N[(t)Bu]Ar)(3) in 95% yield. Conversion of the latter to the terminal cyanide complex NCMo(N[(t)Bu]Ar)(3), which was the subject of a single-crystal X-ray diffraction study, was accomplished in 51% yield upon treatment with a combination of SnCl(2) and Me(2)NSiMe(3).

Coordination-mode control of bound nitrile radical complex reactivity: intercepting end-on nitrile-Mo(III) radicals at low temperature.

Variable temperature equilibrium studies were used to derive thermodynamic data for formation of eta(1) nitrile complexes with Mo(N[(t)Bu]Ar)(3), 1. (1-AdamantylCN = AdCN: DeltaH(degrees) = -6 +/- 2 kcal mol(-1), DeltaS(degrees) = -20 +/- 7 cal mol(-1) K(-1). C(6)H(5)CN = PhCN: DeltaH(degrees) = -14.5 +/- 1.5 kcal mol(-1), DeltaS(degrees) = -40 +/- 5 cal mol(-1) K(-1). 2,4,6-(H(3)C)(3)C(6)H(2)CN = MesCN: DeltaH(degrees) = -15.4 +/- 1.5 kcal mol(-1), DeltaS(degrees) = -52 +/- 5 cal mol(-1) K(-1).) Solution calorimetric studies show that the enthalpy of formation of 1-[eta(2)-NCNMe(2)] is more exothermic (DeltaH(degrees) = -22.0 +/- 1.0 kcal mol(-1)). Rate and activation parameters for eta(1) binding of nitriles were measured by stopped flow kinetic studies (AdCN: DeltaH(on)(++) = 5 +/- 1 kcal mol(-1), DeltaS(on)(++) = -28 +/- 5 cal mol(-1) K(-1); PhCN: DeltaH(on)(++) = 5.2 +/- 0.2 kcal mol(-1), DeltaS(on)(++) = -24 +/- 1 cal mol(-1) K(-1); MesCN: DeltaH(on)(++) = 5.0 +/- 0.3 kcal mol(-1), DeltaS(on)(++) = -26 +/- 1 cal mol(-1) K(-1)). Binding of Me(2)NCN was observed to proceed by reversible formation of an intermediate complex 1-[eta(1)-NCNMe(2)] which subsequently forms 1-[eta(2)-NCNMe(2)]: DeltaH(++)(k1) = 6.4 +/- 0.4 kcal mol(-1), DeltaS(++)(k1) = -18 +/- 2 cal mol(-1) K(-1), and DeltaH(++)(k2) = 11.1 +/- 0.2 kcal mol(-1), DeltaS(++)(k2) = -7.5 +/- 0.8 cal mol(-1) K(-1). The oxidative addition of PhSSPh to 1-[eta(1)-NCPh] is a rapid second-order process with activation parameters: DeltaH(++) = 6.7 +/- 0.6 kcal mol(-1), DeltaS(++) = -27 +/- 4 cal mol(-1) K(-1). The oxidative addition of PhSSPh to 1-[eta(2)-NCNMe(2)] also followed a second-order rate law but was much slower: DeltaH(++) = 12.2 +/- 1.5 kcal mol(-1) and DeltaS(++) = -25.4 +/- 5.0 cal mol(-1) K(-1). The crystal structure of 1-[eta(1)-NC(SPh)NMe(2)] is reported. Trapping of in situ generated 1-[eta(1)-NCNMe(2)] by PhSSPh was successful at low temperatures (-80 to -40 degrees C) as studied by stopped flow methods. If 1-[eta(1)-NCNMe(2)] is not intercepted before isomerization to 1-[eta(2)-NCNMe(2)] no oxidative addition occurs at low temperatures. The structures of key intermediates have been studied by density functional theory, confirming partial radical character of the carbon atom in eta(1)-bound nitriles. A complete reaction profile for reversible ligand binding, eta(1) to eta(2) isomerization, and oxidative addition of PhSSPh has been assembled and gives a clear picture of ligand reactivity as a function of hapticity in this system.

A terminal molybdenum arsenide complex synthesized from yellow arsenic.

A terminal molybdenum arsenide complex is synthesized in one step from the reactive As(4) molecule. The properties of this complex with its arsenic atom ligand are discussed in relation to the analogous nitride and phosphide complexes.

Synthesis and reversible reductive coupling of cationic, dinitrogen-derived diazoalkane complexes.

A series of cationic diazoalkane complexes [4-RC(6)H(4)C(H)NNMo(N[t-Bu]Ar)(3)][AlCl(4)], [1-R][AlCl(4)] (R = NMe(2), Me, H, Br, CN; Ar = 3,5-C(6)H(3)Me(2)) has been prepared by treatment of the N(2)-derived diazenido complex Me(3)SiNNMo(N[t-Bu]Ar)(3) with 4-RC(6)H(4)CHO and 2 equiv of AlCl(3). The structures of [1-H][AlCl(4)] and [1-NMe(2)][AlCl(4)] were determined by X-ray crystallography. The C-N and N-N stretching modes were identified by a combined IR and Raman spectroscopy study, and other physical properties are discussed in detail. The electrochemical reduction potential for [1-R][AlCl(4)] was shown to be linear with the Hammett sigma parameter. This reduction process forms the C-C bonded dimer, mu-(4-RC(6)H(4)C(H)NN)(2)[Mo(N[t-Bu]Ar)(3)](2), that was characterized by X-ray crystallography for R = H. Possible mechanisms for the formation of this dimer are presented. Both electrochemical investigations and quantum chemical calculations are used to describe the odd-electron complex 4-RC(6)H(4)C(H)NNMo(N[t-Bu]Ar)(3), 1-R, that is an intermediate in the formation of [1-R](2). The C-C bond in [1-R](2) is redox-noninnocent and is broken upon oxidation. This reaction was used to prepare [1-H][A] (A = PF(6)(-), OTf(-)), and possible uses of this property in charge-storage devices are discussed.

Shining light on dinitrogen cleavage: structural features, redox chemistry, and photochemistry of the key intermediate bridging dinitrogen complex.

The key intermediate in dinitrogen cleavage by Mo(N[t-Bu]Ar)3, 1 (Ar = 3,5-C6H3Me2), has been characterized by a pair of single crystal X-ray structures. For the first time, the X-ray crystal structure of (mu-N2)[Mo(N[t-Bu]Ar)3]2, 2, and the product of homolytic fragmentation of the NN bond, NMo(N[t-Bu]Ar)3, are reported. The structural features of 2 are compared with previously reported EXAFS data. Moreover, contrasts are drawn between theoretical predictions concerning the structural and magnetic properties of 2 and those reported herein. In particular, it is shown that 2 exists as a triplet (S = 1) at 20 degrees C. Further insight into the bonding across the MoNNMo core of the molecule is obtained by the synthesis and structural characterization of the one- and two-electron oxidized congeners, (mu-N2)[Mo(N[t-Bu]Ar)3]2[B(Ar(F))4], 2[B(Ar(F))4] (Ar(F) = 3,5-C6H3(CF3)2) and (mu-N2)[Mo(N[t-Bu]Ar)3]2[B(Ar(F))4]2, 2[B(Ar(F))4]2, respectively. Bonding in these three molecules is discussed in view of X-ray crystallography, Raman spectroscopy, electronic absorption spectroscopy, and density functional theory. Combining X-ray crystallography data with Raman spectroscopy studies allows the NN bond polarization energy and NN internuclear distance to be correlated in three states of charge across the MoNNMo core. For 2[B(Ar(F))4], bonding is symmetric about the mu-N2 ligand and the NN polarization is Raman active; therefore, 2[B(Ar(F))4] meets the criteria of a Robin-Day class III mixed-valent compound. The redox couples that interrelate 2, 2(+), and 2(2+) are studied by cyclic voltammetry and spectroelectrochemistry. Insights into the electronic structure of 2 led to the discovery of a photochemical reaction that forms NMo(N[t-Bu]Ar)3 and Mo(N[t-Bu]Ar)3 through competing NN bond cleavage and N2 extrusion reaction pathways. The primary quantum yield was determined to be Phi(p) = 0.05, and transient absorption experiments show that the photochemical reaction is complete in less than 10 ns.

Thermodynamic, kinetic, and computational study of heavier chalcogen (S, Se, and Te) terminal multiple bonds to molybdenum, carbon, and phosphorus.

Enthalpies of chalcogen atom transfer to Mo(N[t-Bu]Ar)3, where Ar = 3,5-C6H3Me2, and to IPr (defined as bis-(2,6-isopropylphenyl)imidazol-2-ylidene) have been measured by solution calorimetry leading to bond energy estimates (kcal/mol) for EMo(N[t-Bu]Ar)3 (E = S, 115; Se, 87; Te, 64) and EIPr (E = S, 102; Se, 77; Te, 53). The enthalpy of S-atom transfer to PMo(N[ t-Bu]Ar) 3 generating SPMo(N[t-Bu]Ar)3 has been measured, yielding a value of only 78 kcal/mol. The kinetics of combination of Mo(N[t-Bu]Ar)3 with SMo(N[t-Bu]Ar)3 yielding (mu-S)[Mo(N[t-Bu]Ar)3]2 have been studied, and yield activation parameters Delta H (double dagger) = 4.7 +/- 1 kcal/mol and Delta S (double dagger) = -33 +/- 5 eu. Equilibrium studies for the same reaction yielded thermochemical parameters Delta H degrees = -18.6 +/- 3.2 kcal/mol and Delta S degrees = -56.2 +/- 10.5 eu. The large negative entropy of formation of (mu-S)[Mo(N[t-Bu]Ar)3]2 is interpreted in terms of the crowded molecular structure of this complex as revealed by X-ray crystallography. The crystal structure of Te-atom transfer agent TePCy3 is also reported. Quantum chemical calculations were used to make bond energy predictions as well as to probe terminal chalcogen bonding in terms of an energy partitioning analysis.

Observation of the A1A" state of isocyanogen.

The A1A" state of isocyanogen, CNCN, is observed using photofragment fluorescence excitation spectroscopy in a room temperature cell and in a molecular beam. The spectra are highly congested, but progressions that correspond to the Franck-Condon active C-N-C bending vibration in the excited state are evident. Linewidth measurements indicate that the excited state lifetime is <10 ps. These measurements are consistent with previous ab initio calculations, which predicted a bent excited state with a short lifetime due to predissociation. Although we do not believe that we have observed the origin band of the electronic transition, we place an upper limit of 42,523 cm(-1) on the energy of the excited state zero point level.

A cycle for organic nitrile synthesis via dinitrogen cleavage.

In the presence of NaH, the reaction between N2 and Mo(N[t-Bu]Ar)3 (Ar = 3,5-C6H3Me2) proceeds at room temperature to afford NMo(N[t-Bu]Ar)3 (95%). Lewis acidic silyl triflates (Me3SiOTf + pyridine or (i-Pr)3SiOTf) mediate a reaction between acid chlorides and NMo(N[t-Bu]Ar)3 to yield acyl imidos [RC(O)NMo(N[t-Bu]Ar)3][OTf] (R = Me, 92%; Ph, 75%; t-Bu, 64%). The reduction of [RC(O)NMo(N[t-Bu]Ar)3][OTf] by magnesium anthracene followed by treatment with Me3SiOTf affords molybdenum ketimides, R(Me3SiO)CNMo(N[t-Bu]Ar)3 (R = Me, 82%; Ph, 77%; t-Bu, 46%). Exposing R(Me3SiO)CNMo(N[t-Bu]Ar)3 to SnCl2 or ZnCl2 produces ClMo(N[t-Bu]Ar)3 (71-93% for SnCl2) and RCN (97-99%). Magnesium metal reduces ClMo(N[t-Bu]Ar)3 to Mo(N[t-Bu]Ar)3 (74%), completing a synthetic cycle. New strategies for the functionalization of sterically hindered nitrides and nitrile extrusion from d2 ketimides are presented in the context of a new route for derivatizing N2.