Demographic and Socioeconomic Factors in Prospective Retina-Focused Clinical Trial Screening and Enrollment.

Historically marginalized populations are disproportionately affected by many diseases that commonly affect the retina, yet they have been traditionally underrepresented in prospective clinical trials. This study explores whether this disparity affects the clinical trial enrollment process in the retina field and aims to inform future trial recruitment and enrollment. Age, gender, race, ethnicity, preferred language, insurance status, social security number (SSN) status, and median household income (estimated using street address and zip code) for patients referred to at least one prospective, retina-focused clinical trial at a large, urban, retina-based practice were retrospectively extracted using electronic medical records. Data were collected for the 12-month period from 1 January 2022, through 31 December 2022. Recruitment status was categorized as Enrolled, Declined, Communication (defined as patients who were not contacted, were contacted with no response, were waiting for a follow-up, or were scheduled for screening following a clinical trial referral.), and Did Not Qualify (DNQ). Univariable and multivariable analyses were used to determine significant relationships between the Enrolled and Declined groups. Among the 1477 patients, the mean age was 68.5 years old, 647 (43.9%) were male, 900 (61.7%) were White, 139 (9.5%) were Black, and 275 (18.7%) were Hispanic. The distribution of recruitment status was: 635 (43.0%) Enrolled, 232 (15.7%) Declined, 290 (19.6%) Communication, and 320 (21.7%) DNQ. In comparing socioeconomic factors between the Enrolled and Declined groups, significant odds ratios were observed for age (p < 0.02, odds ratio (OR) = 0.98, 95% confidence interval (CI) [0.97, 1.00]), and between patients who preferred English versus Spanish (p = 0.004, OR = 0.35, 95% CI [0.17, 0.72]. Significant differences between the Enrolled and Declined groups were also observed for age (p < 0.05), ethnicity (p = 0.01), preferred language (p < 0.05), insurance status (p = 0.001), and SSN status (p < 0.001). These factors may contribute to patient participation in retina-focused clinical trials. An awareness of these demographic and socioeconomic disparities may be valuable to consider when attempting to make clinical trial enrollment an equitable process for all patients, and strategies may be useful to help address these challenges.

Loss to Follow-Up Among Patients With Proliferative Diabetic Retinopathy in Clinical Practice.

PURPOSE: To determine the proportion of patients with proliferative diabetic retinopathy (PDR) who were counted as loss to follow-up (LTFU) patients and to investigate predictive factors. DESIGN: Retrospective cohort study. METHODS: Information was collected for 4,423 patients with PDR between April 30, 2012, and April 30, 2017. Two definitions of LTFU were used. Complete LTFU referred to the population who never returned to care within the study period. Interval LTFU referred to the population who did not adhere to clinical recommendations and missed scheduled appointments, resulting in intervals longer than 6 months or 1 year between 2 appointments. Age, average gross income, and insurance were assessed as potential predictors of interval LTFU. RESULTS: Among 4,423 patients with PDR, 2,407 (54.4%) and 2,320 (52.4%) were complete LTFU at 6 months and 1 year, respectively; 782 (17.7%) and 468 (10.6%) patients were interval LTFU for 6 months and 1 year, respectively. Age and average gross income were not found to be significant predictors of interval LTFU. Compared to self-pay, government and private insurance patients were more likely to be interval LTFU at 6 months (government, P = .035; private, P = .005). Private insurance patients were also more likely to be interval LTFU at 1 year (P = .003). CONCLUSIONS: The identified complete LTFU rates were notably high and warrant further study. More than 1 of 6 patients were interval LTFU for at least 6 months, and 1 of 10 patients was interval LTFU for more than 1 year. Insurance status was significant in determining interval LTFU status. Consistent with other analyses, these results indicate that compliance with clinical appointments among patients with PDR is a substantial clinical challenge.

CHOROIDAL NEOVASCULARIZATION SECONDARY TO ALEXANDRITE LASER EXPOSURE.

PURPOSE: To report macular photic trauma after accidental occupational exposure to a 750-nm Alexandrite laser and management of secondary choroidal neovascularization. METHODS: Institutional review board-approved retrospective case report. RESULTS: A 30-year-old woman presented with immediate vision loss in her left eye after direct inadvertent exposure to a single discharge from an occupational 750-nm Alexandrite laser used for laser hair removal. Baseline Snellen visual acuity was 20/40 in the involved left eye. One week after the initial exposure, the patient experienced subjective visual decline to 20/50, was treated with oral prednisone, and then developed a subretinal hemorrhage (SRH) in the setting of choroidal neovascularization 2 weeks later, or 3 weeks after initial trauma. The patient subsequently received 5 intravitreal ranibizumab injections over 25 weeks with resolution of the SRH. Final visual acuity was 20/50. CONCLUSION: The present case documents development and management of subretinal hemorrhage associated with choroidal neovascularization following macular photic trauma after accidental occupational to a 750-nm Alexandrite laser.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION: Role of Prophylactic Topical Ophthalmic Antibiotics.

PURPOSE: To determine the rate of postintravitreal injection endophthalmitis and to assess microbiological features and outcomes with and without the use of peri-intravitreal injection topical ophthalmic antibiotics. METHODS: Consecutive series of endophthalmitis cases retrospectively identified after intravitreal injection at a multicenter, retina-only referral practice (Retina Consultants of Houston) from January 1, 2011 to December 31, 2014. Prophylactic peri-intravitreal injection topical antibiotics were routinely used during the initial 12-month period (January 1, 2011-December 31, 2011) and not used in the final 24-month period (January 1, 2013-December 31, 2014). Main outcome measures were incidence of endophthalmitis, microbiology results, treatment strategies, and visual outcomes. RESULTS: Of 90,339 intravitreal injections, 30 cases of endophthalmitis were identified (endophthalmitis rate = 0.033%; 95% confidence interval, 0.021-0.045%; or approximately 1 of 3,011 intravitreal injections). The most common organisms isolated were coagulase-negative staphylococci (n = 10, 33%), followed by Streptococcus mitis (n = 2, 7%). Fourteen cases (47%) were culture negative. Peri-intravitreal injection topical antibiotic prophylaxis did not decrease the rate of endophthalmitis (0.035% [95% CI, 0.007-0.064%] with antibiotic use versus 0.021% [95% CI, 0.008-0.033%] without antibiotic use; P = 0.261). CONCLUSION: The risk of endophthalmitis after intravitreal injection remains low, with coagulase-negative staphylococci and Streptococcus mitis the most common bacterial isolates identified. Prophylactic peri-intravitreal injection topical ophthalmic antibiotic use did not decrease the endophthalmitis rate.

The chemoselective reactions of tyrosine-containing G-protein-coupled receptor peptides with [Cp*Rh(H2O)3](OTf)2, including 2D NMR structures and the biological consequences.

The bioconjugation of organometallic complexes with peptides has proven to be a novel approach for drug discovery. We report the facile and chemoselective reaction of tyrosine-containing G-protein-coupled receptor (GPCR) peptides with [Cp*Rh(H(2)O)(3)](OTf)(2), in water, at room temperature, and at pH 5-6. We have focused on three important GPCR peptides; namely, [Tyr(1)]-leu-enkephalin, [Tyr(4)]-neurotensin(8-13), and [Tyr(3)]-octreotide, each of which has a different position for the tyrosine residue, together with competing functionalities. Importantly, all other functional groups present, i.e., amino, carboxyl, disulfide, phenyl, and indole, were not prominent sites of reactivity by the Cp*Rh tris aqua complex. Furthermore, the influence of the Cp*Rh moiety on the structure of [Tyr(3)]-octreotide was characterized by 2D NMR, resulting in the first representative structure of an organometallic-peptide complex. The biological consequences of these Cp*Rh-peptide complexes, with respect to GPCR binding and growth inhibition of MCF7 and HT29 cancer cells, will be presented for [(η(6)-Cp*Rh-Tyr(1))-leu-enkephalin](OTf)(2) and [(η(6)-Cp*Rh-Tyr(3))-octreotide](OTf)(2).

Fluoroponytailed crown ethers and quaternary ammonium salts as solid-liquid phase transfer catalysts in organic synthesis.

Fluorous derivatives of dibenzo-18-crown-6 ether were prepared, and then successfully applied in representative solid-liquid phase transfer catalysis reactions, which were performed in standard organic solvents, such as chlorobenzene and toluene, as well as in fluorous solvents, such as perfluoro-1,3-dimethylcyclohexane. It was clearly shown that properly designed fluoroponytailed crown ethers could promote the disintegration of the crystal lattice of alkali salts, and transfer anions from the solid surface into an apolar, non-coordinating perfluorocarbon phase, for phase transfer catalysis reactions in organic synthesis. Furthermore, 3,5-bis(perfluorooctyl)benzyl bromide and triethylamine were reacted under mild conditions to provide an analogue of the versatile phase transfer catalyst, benzyltriethylammonium chloride, containing two fluoroponytails. This fluoroponytailed quaternary ammonium salt was also successfully employed as a catalyst in a variety of organic reactions conducted under solid-liquid phase transfer catalysis conditions, without a perfluorocarbon phase. Thus, being both hydrophobic and lipophobic, fluorous crown ethers and ammonium salts, could be rapidly recovered in quantitative yields, and reused without loss of activity, over several reaction cycles.

Synthetic and mechanistic pathways of cis and trans-hydroxytamoxifen drug derivatives reacting with Cp*Rh complexes that involve η1-N, η2-N,O, η1-O, and η6 bonding modes, via a novel N-π rearrangement; relative binding affinities and computer docking studies of cis and trans-η6-Cp*Rh-hydroxytamoxifen complexes at the estrogen, ERα and ERß receptors, and growth inhibition to breast cancer cells.

The reactions of the breast cancer drug metabolite derivatives of tamoxifen, cis and trans-hydroxytamoxifen, cis-1 and trans-2, with [Cp*Rh(L)(3)](2+) complexes (L = H(2)O or MeOH), in CH(2)Cl(2) and CH(3)OH solvents, initially provided the kinetic η(1)-N complexes, cis-4 (OTf(-), CH(3)OH) and trans-5 (OTf(-), CH(3)OH), which underwent a novel, regioselective, intramolecular N-π rearrangement to give the cis and trans-η(6)-phenol substituted complexes, cis-6 and trans-7, via η(2)-N,O, η(1)-O, and ether aromatic ring η(6) intermediates. Recent density functional theory (DFT) calculations showed a preferred ground state for η(1)-N; η(2)-N,O; η(1)-O; and the η(6) complexes, including the prominent roles of the triflate anion (OTf(-)), and solvent molecules (CH(2)Cl(2) and CH(3)OH), and provided further steric, electronic, and thermodynamic data on the mechanism of the N-π rearrangement. The η(6) complex, cis-6, was shown to be an antagonist for ERα estrogen receptor binding, in a competition experiment with the female hormone, estradiol; therefore, computer docking studies of this biologically active complex at the estrogen receptors, ERα and ERß, also provided information on the binding modes and thermodynamic parameters, while bioassay results provided growth inhibition data on both hormone dependent and independent breast cancer cell lines.

Use of nepafenac (Nevanac) in combination with intravitreal anti-VEGF agents in the treatment of recalcitrant exudative macular degeneration requiring monthly injections.

PURPOSE: The purpose of this study is to determine the efficacy of combining topical nepafenac with monthly intravitreal injections of ranibizumab or bevacizumab in the treatment of recalcitrant exudative macular degeneration. METHODS: This was a retrospective, consecutive case series of patients with exudative macular degeneration requiring maintenance therapy of antivascular endothelial growth factor ( anti-VEGF) injections at least every 6 weeks, who were started on topical nepafenac. Despite frequent anti-VEGF dosing, all patients included in the study had persistence of any combination of the following: intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Patients underwent pinhole visual acuity, clinical exam, and optical coherence tomography (OCT) at baseline and every follow-up visit. Response to therapy was graded by reviewing quantitative and qualitative OCT data, and statistical analysis was done with paired Student's t-test. RESULTS: Twenty-five patients (average age 77; 14 male and 11 female) were reviewed; the mean number of previous injections was 17.4 (range 3-31). Baseline mean visual acuity was 20/55, and final mean visual acuity after 3 months of treatment was 20/51 (P = 0.13). Monthly mean central foveal thickness measurements were 248, 250, 257, and 247 µm (P = 0.53) at baseline, 1, 2, and 3 months, respectively. By the end of the 3-month time point, qualitative OCT findings on 13 patients treated with nepafenac were classified as stable, 10 as better, and 2 as worse. CONCLUSIONS: There was no significant change in visual acuity or quantitative OCT measurements, but there appeared to be a mild trend toward improved anatomy and qualitative OCT findings when topical nepafenac was added to monthly anti-VEGF injections in patients with persistent intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Further prospective studies with longer follow-up may be warranted.

Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

PURPOSE: While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. METHODS: Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. RESULTS: Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. CONCLUSION: Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

Lucentis using Visudyne study: determining the threshold-dose fluence of verteporfin photodynamic therapy combined with intravitreal ranibizumab for exudative macular degeneration.

PURPOSE: Combination verteporfin photodynamic therapy (vPDT) and antivascular endothelial growth factor (anti-VEGF) therapy may decrease the need for injections while maintaining visual acuity in exudative age-related macular degeneration. This pilot study was designed to determine the threshold fluence dose of vPDT (the dose required to demonstrate an effect on choroidal perfusion) combined with ranibizumab. METHODS: Seven patients were randomized to sham vPDT (two patients), 20% fluence vPDT (two patients), or 40% fluence vPDT (three patients) in combination with three-monthly intravitreal 0.5 mg ranibizumab injections. Intravitreal ranibizumab was reinjected if disease activity was seen on fluorescein angiography, optical coherence tomography, or clinical examination. Indocyanine green-determined choroidal hypoperfusion was graded in a masked fashion. RESULTS: Patients with 20% vPDT had mild hypoperfusion defects at seven days that resolved by week 4 (threshold dose); patients with 40% fluence vPDT had marked hypoperfusion at seven days that persisted as long as 12 months. Recruitment was stopped after limited efficacy was observed. One patient with 20% fluence vPDT lost 19 letters at one year; no other patient lost or gained >10 letters. Central retinal thickness decreased in six of seven patients, but ranibizumab injections did not decrease. CONCLUSION: This pilot study shows that the threshold fluence dose of vPDT (when combined with ranibizumab) is approximately 20% standard fluence, and that mild and transient choroidal hypoperfusion can occur. Forty percent fluence vPDT causes a more prolonged and striking hypoperfusion. Despite hypoperfusion, no decrease in visual acuity or injections required was noted, suggesting that even higher fluence levels of vPDT may be necessary to decrease the number of anti-VEGF injections.

A DFT study on the mechanism of a novel, regioselective, intramolecular N-pi rearrangement of cis and trans-eta1-N-Cp*Rh-hydroxytamoxifen complexes to their eta6 derivatives; potential breast cancer pharmaceuticals, and fluorescent probes.

The previously reported reactions of cis and trans-hydroxytamoxifen drug derivatives, 1 and 2, with [Cp*Rh(L)(3)](2+) complexes (L = H(2)O, CH(3)OH), initially provided the kinetically controled eta(1)-N complexes, 4(OTf, CH(3)OH) and 5(OTf, CH(3)OH), which underwent a novel, intramolecular, regioselective N-pi rearrangement to provide the eta(6) complexes, 6 and 7. A dramatic solvent effect was also observed on the rate of this N-pi rearrangement in CH(3)OH or CH(2)Cl(2). Therefore, a DFT study was conducted that provided further mechanistic and thermodynamic data on this N-pi rearrangement. The preferred structures of both the eta(1)-N and eta(6) complexes in the two solvents were determined, and a thorough analysis of their geometries and electronic structures has been provided. The influence of the solvent on the N-pi rearrangement was studied by including the solvent both implicitly using a PCM model, and explicitly by introducing the counterion and/or the solvent molecules into the inner and outer coordination spheres of the complexes. It was shown that the triflate (OTf(-)) counterion was strongly bound in the inner coordination sphere of the eta(1)-N complexes, 4(OTf) and 5(OTf), and in the outer sphere of the coordinatively saturated eta(6) complexes, 6 and 7, especially in non-polar media. The cleavage of the ionic Cp*Rh-OTf bond was found to be the rate-limiting step in the N-pi rearrangement. The thermodynamic results suggested that the eta(6) complexes were more stable than the eta(1)-N complexes in CH(2)Cl(2) and in CH(3)OH at elevated temperatures. The opposite relationship for the stabilities of the eta(1)-N complexes was found in CH(3)OH at room temperature, thus corroborating the experimental results that the N-pi rearrangement did not occur, under these conditions. A plausible mechanistic pathway for the N-pi rearrangement was proposed from our extensive DFT studies, that included several important intermediates and transition states, and provided a unique view of this novel transformation.

Selected clinical comparisons of spectral domain and time domain optical coherence tomography.

The authors report four cases where spectral domain optical coherence tomography (SD-OCT) imaged pathology not captured by time domain optical coherence tomography (TD-OCT). These cases include one of angioid streaks, two of juxtafoveal telangiectasia, and one of age-related macular degeneration. In each case, the improved images provided by SD-OCT changed either the management of the patient or the counseling of their disease process.

Studies on the reactivity of organometallic Ru-, Rh- and Os-pta complexes with DNA model compounds.

The reactions of arene-metal complexes (arene=p-cymene, benzene or pentamethylcyclopentadienyl, metal=Ru, Rh or Os), including 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decanephosphine (pta) and chloro co-ligands, with 9-methylguanine, adenine, and a series of nucleosides were studied in water to ascertain the binding modes. The products were characterized by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Tandem mass spectrometry was found to provide excellent information on preferential binding sites. In general, the N7 position on guanine (the most basic site) was found to be the preferred donor atom for coordination to the metal complexes. The X-ray structures of the precursor complexes, [(eta5-C10H15)RhCl(pta-Me)2]Cl2, [(eta6-C10H14)OsCl(pta)2]Cl, and [(eta6-C6H6)OsCl2(CH3CN)], are also reported.

Long-term stability of circumferential silicone sponge scleral buckling exoplants.

PURPOSE: The historical extrusion/explantation rate of silicone sponge scleral buckle exoplants is 3.5 to 24.4%. This contrasts with the published 0.6 to 1.2% explantation rate of solid silicone elements. Previously reported silicone sponge exoplants studies were noncircumferential (quadrantic or multiple). This study was undertaken to assess the long-term stability of 360 degrees circumferentially placed 3 x 5 mm silicone sponge exoplants. METHODS: Interventional case series of 840 consecutive circumferentially placed 3 x 5 mm silicone sponge exoplants. A retrospective review of operative reports and patient charts was performed. RESULTS: A total of 552 patients had documented follow-up over 1 year. Median follow-up was 32.8 months. Six patients underwent removal of the scleral buckling element (two for diplopia, one acute postoperative infection, and three for extrusion). Median time to removal was 7.3 months. Extenuating circumstances contributed to two of the three extrusions. Of the entire series, fewer than 1% of patients required removal of the silicone sponge implant. Excluding patients with less than 1 year of documented follow-up, the long-term infection/extrusion rate was 0.7%. CONCLUSIONS: Circumferentially placed silicone scleral buckling sponge elements are very stable and are well tolerated. The explantation/extrusion rate is comparable to published solid silicone element series.

Fluorocarbon soluble copper(II) carboxylate complexes with nonfluoroponytailed nitrogen ligands as precatalysts for the oxidation of alkenols and alcohols under fluorous biphasic or thermomorphic modes: structural and mechanistic aspects.

This fluorous biphasic catalysis (FBC) contribution was focused on the synthesis and characterization of new fluorous soluble R(f)-Cu(II) carboxylate complexes containing nonfluoroponytailed ligands and defines their role as precatalysts for the FBC oxidation of alkenols and alcohols in the presence of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)/O(2). In this FBC approach, we have utilized the phase-switching technique of Vincent et al. (J. Am. Chem. Soc. 2002, 124, 12942) to solubilize the nonfluoroponytailed ligands, N-1,4,7-Me(3)TACN, 2, and N-1,4,7-pentamethyldiethylenetriamine (PMDETA), 3, by reaction with a fluorous solvent-soluble copper (II) dimeric complex, [Cu({C(8)F(17)(CH(2))(2)}(2)CHCO(2))(2)](2), 1. Moreover, the reaction of nonfluoroponytailed ligands 2 and 3 with 1 afforded new perfluoroheptane-soluble Cu(II) complexes, [Cu({C(8)F(17)(CH(2))(2)}(2)CHCO(2))(2)(2)], 4, and [Cu({C(8)F(17)(CH(2))(2)}(2)CHCO(2))(2) (3)], 5, respectively. The known Cu(II) complex, 1, was further characterized by electron paramagnetic resonance (EPR) spectroscopy confirming its dimeric structure, while 4 and 5 were characterized by elemental analysis, IR, diffuse reflectance UV-vis, and EPR spectroscopy. Furthermore, 1, 4, and 5 were evaluated as precatalysts for alkenol and alcohol oxidation. The oxidation reactions of alkenols and alcohols in the presence of TEMPO/O(2) proceeded under FBC conditions for 1, 4, and 5, but 1-octanol was unreactive under single-phase FBC conditions at 90 degrees C with TEMPO/O(2). The thermomorphic property of 5, soluble in chlorobenzene/toluene at 90 degrees C but insoluble at room temperature, was also evaluated in the selective oxidation of p-nitrobenzyl alcohol to p-nitrobenzaldehyde. Plausible mechanisms concerning these FBC/thermomorphic oxidation reactions will be discussed.

Polyfluorinated quaternary ammonium salts of polyoxometalate anions: fluorous biphasic oxidation catalysis with and without fluorous solvents.

[reaction: see text] Polyfluorinated quaternary ammonium cations, [CF(3)(CF(2))(7)(CH(2))(3)](3)CH(3)N(+) (R(F)N(+)), were synthesized and used as countercations for the [WZnM(2)(H(2)O)(2)(ZnW(9)O(34))(2)](12)(-) (M = Mn(II), Zn(II)) polyoxometalate. The (R(F)N(+))(12)[WZnM(2)(H(2)O)(2)(ZnW(9)O(34))(2)] compounds were fluorous biphasic catalysts for alcohol and alkenol oxidation, and alkene epoxidation with aqueous hydrogen peroxide. Reaction protocols with or without a fluorous solvent were tested. The catalytic activity and selectivity was affected by both the hydrophobicity of the solvent and the substrate.

Fluorous biphasic catalysis: synthesis and characterization of copper(I) and copper(II) fluoroponytailed 1,4,7-Rf-TACN and 2,2'-Rf-bipyridine complexes--their catalytic activity in the oxidation of hydrocarbons, olefins, and alcohols, including mechanistic implications.

In this contribution on fluorous biphasic catalysis (FBC), we present the synthesis and characterization of new copper complexes, and define their role, as precatalysts, in the FBC oxidation of hydrocarbons, olefins, and alcohols. Thus the previously reported, but poorly characterized, fluoroponytailed ligand, 2,2'-R(f)-bipyridine (R(f)=-(CH(2))(3)C(8)F(17)) 2, as well as the new Cu(II) fluoroponytailed carboxylate synthon complex [Cu(C(8)F(17)(CH(2))(2)CO(2))(2)] 3, will be addressed. Moreover, the reaction of previously described ligands, 1,4,7-R(f)-TACN 1, or 2,2'-R(f)-bipyridine 2 with 3 afforded new perfluoroheptane-soluble Cu(II) complexes, [Cu(C(8)F(17)(CH(2))(2)CO(2))(2)(R(f)-tacn)] 4 and [Cu(C(8)F(17)(CH(2))(2)CO(2))(2)(R(f)-bpy)] 5, respectively. The reaction of 1 with [Cu(CH(3)CN)(4)]PF(6) or [CuCl] provided new Cu(I) complexes, which could be isolated and fully characterized as [Cu(R(f)-tacn)X']X, in which X=PF(6) (6) or X'=Cl (7) (soluble in perfluoroheptane). The Cu(II) and Cu(I) complexes, 4-7, were characterized by elemental analysis, mass spectrometry, and IR, diffuse reflectance UV/Vis, and EPR spectroscopies; complex 7 was also characterized by (1)H and (19)F[(1)H] NMR spectroscopy. Complexes 4 and 5, as well as 6 and 7 generated in situ, were evaluated as precatalysts for hydrocarbon and olefin functionalization. The oxidation reactions of these substrates in the presence of the necessary oxidants, tert-butyl hydroperoxide (TBHP) and oxygen gas, proceeded under FBC conditions for 5, 7, and Cu(I) salts with 2. However, the complexes with ligand 2 could not be recycled, owing to significant ligand dissociation. The Cu(II) complex 4, with the ligand 1, provide the oxidation of 4-nitrobenzyl alcohol to 4-nitrobenzaldehyde under single-phase FBC conditions at 90 degrees C with TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxy) and O(2); the precatalyst 4, can be utilized for an additional four catalytic cycles without loss of activity. Plausible mechanisms concerning these FBC oxidation reactions will be discussed.

Biomimetic Oxidation Studies. 11. Alkane Functionalization in Aqueous Solution Utilizing in Situ Formed [Fe(2)O(eta(1)-H(2)O)(eta(1)-OAc)(TPA)(2)](3+), as an MMO Model Precatalyst, Embedded in Surface-Derivatized Silica and Contained in Micelles.

The biomimetic, methane monooxygenase enzyme (MMO) precatalyst, [Fe(2)O(eta(1)-H(2)O)(eta(1)-OAc)(TPA)(2)](3+) (TPA = tris[(2-pyridyl)methyl]amine), 1, formed in situ at pH 4.2 from [Fe(2)O(&mgr;-OAc)(TPA)(2)](3+), 2, was embedded in an amorphous silicate surface modified by a combination of hydrophilic poly(ethylene oxide) and hydrophobic poly(propylene oxide). The resulting catalytic assembly was found to be a biomimetic model for the MMO active site within a hydrophobic macroenvironment, allowing alkane functionalization with tert-butyl hydroperoxide (TBHP)/O(2) in an aqueous reaction medium (pH 4.2). For example, cyclohexane was oxidized to a mixture of cyclohexanone, cyclohexanol, and cyclohexyl-tert-butyl peroxide, in a ratio of approximately 3:1:2. The balance between poly(ethylene oxide) and poly(propylene oxide), tethered on the silica surface, was crucial for maximizing the catalytic activity. The silica-based catalytic assembly showed reactivity somewhat higher in comparison to an aqueous micelle system utilizing the surfactant, cetyltrimethylammonium hydrogen sulfate at its critical micelle concentration, in which functionalization of cyclohexane with TBHP/O(2) in the presence of 1 was also studied at pH 4.2 and was found to provide similar products: cyclohexanol, cyclohexanone, and cyclohexyl-tert-butyl peroxide, in a ratio of approximately 2:3:1. Moreover, the mechanism for both the silica-based catalytic assembly and the aqueous micelle system was found to occur via the Haber-Weiss process, in which redox chemistry between 1 and TBHP provides both the t-BuO(*)() and t-BuOO(*)()( )()radicals. The t-BuO(*)()( )()radical initiates the C-H functionalization reaction to form the carbon radical, followed by O(2) trapping, to provide cyclohexyl hydroperoxide, which produces the cyclohexanol and cyclohexanone in the presence of 1, whereas the coupling product emanates from t-BuOO(*)() and cyclohexyl radicals. A discussion concerning both approaches for alkane functionalization in water will be presented.