Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE) in military service members: a prospective, observational study protocol.

BACKGROUND: Non-battle related musculoskeletal injuries (MSKI) are one of the primary medical issues diminishing Service member medical readiness. The MSKI problem is challenging because it is difficult to assess all of the factors that increase MSKI risk and influence post-MSKI outcomes. Currently, there are no high-throughput, clinically-feasible, and comprehensive assessments to generate patient-centric data for informing pre- and post-MSKI risk assessment and mitigation strategies. The objective of the "Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE)" study is to develop a comprehensive suite of clinical assessments to identify the patient-specific factors contributing to MSKI risks and undesired post-MSKI outcomes. METHODS: This is a phased approach, multi-center prospective, observational study (ClinicalTrials.gov number: NCT05111925) to identify physical and psychosocial factors contributing to greater MSKI risk and undesired post-MSKI outcomes, and to identify and validate a minimal set of assessments to personalize risk mitigation and rehabilitation strategies. In Phase I, one cohort (n = 560) will identify the physical and psychosocial factors contributing to greater MSKI risks (single assessment), while a second cohort (n = 780) will identify the post-MSKI physical and psychosocial factors contributing to undesired post-MSKI outcomes (serial assessments at enrollment, 4 weeks post-enrollment, 12 weeks post-enrollment). All participants will complete comprehensive movement assessments captured via a semi-automated markerless motion capture system and instrumented walkway, joint range of motion assessments, psychosocial measures, and self-reported physical fitness performance and MSKI history. We will follow participants for 6 months. We will identify the minimum set of clinical assessments that provide requisite data to personalize MSKI risk mitigation and rehabilitation strategies, and in Phase II validate our optimized assessments in new cohorts. DISCUSSION: The results of this investigation will provide clinically relevant data to efficiently inform MSKI risk mitigation and rehabilitation programs, thereby helping to advance medical care and retain Service members on active duty status. TRIAL REGISTRATION: PREPARE was prospectively registered on ClinicalTrials.gov (NCT05111925) on 5 NOV 2021, prior to study commencement.

The crippled brain that prolonged the Civil War: General Joseph Hooker's concussions at Chancellorsville.

President Lincoln appointed General Joseph Hooker to command the Army of the Potomac in January 1863. In April 1863, Hooker had 130,000 men compared to the Confederate Army's 60,000. The Union forces had more food, clothing, and ammunition. On a decisive day of the Chancellorsville campaign, as Hooker stood on his headquarters porch, a cannonball struck the pillar against which he was leaning. He was hurled to the floor, stunned and senseless. Unconsciousness followed a lucid interval, requiring rest, when another cannonball struck near him. Half of the army was not thrust into battle, resulting in retreat, because Hooker was not capable of commanding. Hooker's army missed the opportune time to attack; the order was never received because Hooker suffered a traumatic brain injury. Under current military protocol, Hooker would not be allowed to return to participation. During this crucial period a reporter stated, "the precious hour passed, while our army was without a head." The Chancellorsville campaign resulted in Union retreat. Hooker's disabling traumatic brain injury prevented him from giving orders and changing the battle's outcome. Had the general not sustained a concussion, the Civil War probably would have ended earlier.

Observation of a Cu(II)(2) (µ-1,2-peroxo)/Cu(III)(2) (µ-oxo)(2) equilibrium and its implications for copper-dioxygen reactivity.

Synthesis of small-molecule Cu2 O2 adducts has provided insight into the related biological systems and their reactivity patterns including the interconversion of the Cu(II) 2 (µ-η(2) :η(2) -peroxo) and Cu(III) 2 (µ-oxo)2 isomers. In this study, absorption spectroscopy, kinetics, and resonance Raman data show that the oxygenated product of [(BQPA)Cu(I) ](+) initially yields an "end-on peroxo" species, that subsequently converts to the thermodynamically more stable "bis-µ-oxo" isomer (Keq =3.2 at -90 °C). Calibration of density functional theory calculations to these experimental data suggest that the electrophilic reactivity previously ascribed to end-on peroxo species is in fact a result of an accessible bis-µ-oxo isomer, an electrophilic Cu2 O2 isomer in contrast to the nucleophilic reactivity of binuclear Cu(II) end-on peroxo species. This study is the first report of the interconversion of an end-on peroxo to bis-µ-oxo species in transition metal-dioxygen chemistry.

Musculoskeletal Injury Risk Stratification: A Traffic Light System for Military Service Members.

Risk factor identification is a critical first step in informing musculoskeletal injury (MSKI) risk mitigation strategies. This investigation aimed to determine if a self-reported MSKI risk assessment can accurately identify military service members at greater MSKI risk and determine whether a traffic light model can differentiate service members' MSKI risks. A retrospective cohort study was conducted using existing self-reported MSKI risk assessment data and MSKI data from the Military Health System. A total of 2520 military service members (2219 males: age 23.49 ± 5.17 y, BMI 25.11 ± 2.94 kg/m2; and 301 females: age 24.23 ± 5.85 y, BMI 25.59 ± 3.20 kg/m2, respectively) completed the MSKI risk assessment during in-processing. The risk assessment consisted of 16 self-report items regarding demographics, general health, physical fitness, and pain experienced during movement screens. These 16 data points were converted to 11 variables of interest. For each variable, service members were dichotomized as at risk or not at risk. Nine of the 11 variables were associated with a greater MSKI risk and were thus considered as risk factors for the traffic light model. Each traffic light model included three color codes (i.e., green, amber, and red) to designate risk (i.e., low, moderate, and high). Four traffic light models were generated to examine the risk and overall precision of different cut-off values for the amber and red categories. In all four models, service members categorized as amber [hazard ratio (HR) = 1.38-1.70] or red (HR = 2.67-5.82) were at a greater MSKI risk. The traffic light model may help prioritize service members who require individualized orthopedic care and MSKI risk mitigation plans.

Treatment Trends and Inpatient Mortality in Isolated Severe Traumatic Brain Injury Using the National Trauma Data Bank.

BACKGROUND: Severe traumatic brain injury (TBI) remains a leading cause of morbidity and mortality. Despite recommendations from the Brain Trauma Foundation, there is wide variability in treatment paradigms for severe TBI. We aimed to elucidate the variability of treatment, particularly neurosurgical procedures and how it affects mortality. METHODS: Adult patients (<65 years old) with a severe isolated TBI who were treated at an American College of Surgeons level I trauma center were identified in the National Trauma Data Bank for the years 2007-2016. International Classification of Diseases, Ninth Revision procedure codes were used to identify primary treatment approaches: intracranial pressure (ICP) monitoring and cranial surgery (craniotomy/craniectomy). RESULTS: Among 25,327 patients with severe isolated TBI, 14.0% underwent ICP and 18.0% underwent cranial surgery. ICP monitoring reduced the odds of mortality (odds ratio 0.89, 95% confidence interval [0.81, 0.98]), but not the extent of cranial surgery (odds ratio 0.71, 95% confidence interval [0.65, 0.77]). CONCLUSIONS: Brain Trauma Foundation guidelines recommend placement of an ICP monitor for severe TBI; however, only 14% of patients with isolated, severe TBI underwent ICP monitoring in 2007-2016. ICP monitoring and cranial surgery decrease the odds of inpatient mortality in patients with severe TBI.

Novel Lateral Approach for MIS Sacroiliac Joint Arthrodesis: An Assessment of Feasibility and Outcomes.

OBJECTIVE: The prevalence of physicians experiencing work-related musculoskeletal disorders is high. Traditionally, minimally invasive surgery (MIS) sacroiliac joint (SIJ) fusions are performed with the patient oriented in the prone position, with an incision made inferior to the iliac crest. However, a novel technique that orients the patient in the lateral decubitus position has the potential of significantly enhancing ergonomics and ease of approach. The primary objectives of this study were to quantify surgical parameters, describe this 'lateral-decubitus MIS' technique, and identify imaging angle parameters that predict feasibility. METHODS: A prospective cohort of patients who underwent MIS SIJ arthrodesis in the lateral decubitus position was evaluated at a single institution between 2017 and 2020. Medians and ranges of intraoperative blood loss, operative time, revision rate, infection, and total radiation dose were recorded. Sacral inlet and outlet angles were defined and collected to assess for operative candidacy. RESULTS: Thirty-nine cases were identified in 34 patients who underwent the technique with an age range of 31-78 years. Median blood loss was 22.5 mL, operating room time was 32.5 minutes, and radiation dose was 30.9 rads. Average sacral inlet was 24.51° and average sacral outlet was 65.44°. Median length of stay was 0.94 days. No cases were aborted or required revision. A total of 93% of study participants reported improvement in pain. Operative parameters were comparable to the traditional prone approach. CONCLUSIONS: The aim was to provide an insight into outcomes and metrics observed from pioneering this style of procedure. A future study comparing traditional perioperative parameters together with surgical ergonomics is needed.

Free Tissue Transfer for Repair of Chronic Esophageal Perforations.

OBJECTIVE: Anterior cervical discectomy and fusion have become a common intervention for cervical spine stabilization. However, complications can cause life-threatening morbidity. Among them, esophageal perforation is associated with severe morbidity, including dysphagia, malnutrition, and infection with the potential development of mediastinitis. Presentation is variable but often results in chronic morbidity. Herein we examine our experiences in the management of esophageal perforation with microvascular free tissue transfer. STUDY DESIGN: Retrospective review from January 2013 to September 2020. SETTING: Single academic tertiary care center. METHODS: This study comprised all patients (age, 41-73 years) undergoing free tissue transfer for the repair of chronic esophageal perforation secondary to anterior cervical discectomy and fusion at an academic tertiary care center. Four patients underwent repair via vastus lateralis myofascial onlay grafting for defects ≤2 cm in greatest dimension, while 1 patient underwent a fasciocutaneous radial forearm free flap repair of an 11 × 5-cm defect. RESULTS: Defect location ranged from hypopharynx to cervical esophagus. Mean operative time was 6.2 hours; the average length of stay for all patients was 6.6 days. Of 5 patients, 1 required additional hardware placement for spine stabilization. All patients underwent gastrostomy tube placement to bypass the surgical site during healing, and all eventually resumed an oral diet postoperatively. Recurrent fistula occurred in 1 of 5 patients. No flap failures were encountered in the study population. CONCLUSION: Vastus lateralis myofascial onlay grafting and fasciocutaneous radial forearm free flap are robust, relatively low-morbidity interventions with a high success rate for definitive repair of chronic esophageal perforation. Repair should be undertaken in concert with a spine surgeon for management of the cervical spine.

Pituitary Metastatic Composite Tumors: A Case Report with Next-Generation Sequencing and Review of the Literature.

BACKGROUND: While pituitary tumors are well understood, little research has been done on metastasis from primary tumors into pituitary adenomas, also known as composite tumors. Because only 34 cases of composite tumors have been reported to date, we hope to better characterize these tumors by reviewing cases reported in the literature and reviewed our own documented case, which includes next-generation sequencing. Case Presentation. A 74-year-old man presented to the emergency department with left vision loss for 3 months. He had a history of colon cancer treated with colectomy and clear cell renal carcinoma treated with left nephrectomy. A preoperative MRI demonstrated growth of a peripherally enhancing, centrally necrotic mass with sellar expansion measuring 5.7 × 3.1 × 3.0 cm. Given these findings, an endoscopic endonasal transsphenoidal resection was performed. Histological assessment revealed a composite tumor: one neoplasm was a nonfunctioning pituitary adenoma, and another neoplasm was a clear cell carcinoma. Next-generation sequencing demonstrated that the tumors shared mutations in VHL and Notch2. The patient died 2 months later from systemic metastatic cancer. CONCLUSION: From our literature review, most metastatic lesions in these composite tumors originated from neoplasms of the lung and kidney. Approximately 63% patients presented with ophthalmoplegia as the initial symptom while 23% displayed hormonal abnormalities. Postoperative mortality had a median of 3.5 months. In our patient, the presence of VHL and Notch2 mutations in both tumors highlights the possibility of using next-generation sequencing to help identify therapeutic targets even in complex composite neoplasms.

Neurosurgical management of perineural metastases: A case series and review of the literature.

BACKGROUND: Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and underreported, phenomenon. Adding complexity to reaching a diagnosis and treating perineural spread (PNS) is the finding that patients may have no known primary tumor, history of skin cancer, and/or incidental PNI in the primary tumor. These delays in diagnosis and treatment are further compounded by an already slow disease process and often require multidisciplinary care with combinations of stereotactic radiosurgery, surgical resection, and novel treatments such as checkpoint inhibitors. METHODS: Six patients with metastatic cancer to the cranial nerves who underwent Gamma Knife radiosurgery (GKRS) treatment were chosen for retrospective analysis. This information included age, gender, any past surgeries (both stereotactic and regular surgery), dose of radiation and volume of the tumor treated in the GKRS, date of PNS, comorbidities, the patient follow-up, and pre- and post-GKRS imaging. The goal of the follow-up with radiographing imaging was to assess the efficacy of GKSS. RESULTS: The clinical course of six patients with PNS is presented. Patients followed variable courses with mixed outcomes: two patients remain living, one was lost to follow-up, and three expired with a median survival of 12 months from date of diagnosis. Patients at our institution are ideally followed for life. CONCLUSION: Given the morbidity and mortality of PNS of cancer, time is limited, and further understanding is required to improve outcomes. Here, we provide a case series of patients with PNS treated with stereotactic radiosurgery, discuss their clinical courses, and review the known literature.

X-ray absorption spectroscopic and theoretical studies on (L)2[Cu2(S2)n]2+ complexes: disulfide versus disulfide(*1-) bonding.

Cu K-, Cu L-, and S K-edge X-ray absorption spectroscopic (XAS) data have been combined with density functional theory (DFT) calculations on [{(TMPA)Cu}2S2](ClO4)2 (1), [{Cu[HB(3,5-Pr(i)2pz)3]}2(S2)] (2), and [{(TMEDA)Cu}2(S2)2](OTf)2 (3) to obtain a quantitative description of their ground state wavefunctions. The Cu L-edge intensities give 63 and 37% Cu d-character in the ground state of 1 and 2, respectively, whereas the S K-pre-edge intensities reflect 20 and 48% S character in their ground states, respectively. These data indicate a more than 2-fold increase in the total disulfide bonding character in 2 relative to 1. The increase in the number of Cu-S bonds in 2 (mu-eta(2):eta(2) S2(2-) bridge) compared to 1 ((mu-eta(1):eta(1) S2(2-) bridge) dominantly determines the large increase in covalency and Cu-disulfide bond strength in 2. Cu K- and L- and S K-pre-edge energy positions directly demonstrate the Cu(II)/(S2(-))2 nature of 3. The two disulfide(*1-)'s in 3 undergo strong bonding interactions that destabilize the resultant filled antibonding pi* orbitals of the (S2(-))2 fragment relative to the Cu 3d levels. This leads to an inverted bonding scheme in 3 with dominantly ligand-based holes in its ground state, consistent with its description as a dicopper(II)-bis-disulfide(*1-) complex.

Conservative treatment of a proximal full-thickness biceps brachii muscle tear in a special operations soldier.

BACKGROUND: A transection of the short head of the biceps brachii muscle is an uncommon injury seen among outpatient sports physical therapy clinics. The highest rate of occurrence and the majority of literature that discusses this specific injury are related to US military parachuting. The purpose of this case report is to outline the episode of care from 2 days after the injury through 6 months of conservative treatment, which consisted of therapeutic exercise, manual therapy, and cryotherapy, within an outpatient sports physical therapy clinic in a military setting. CASE DESCRIPTION: This case report outlines the initial evaluation, diagnostic imaging, treatment, and 6-month follow-up measures for a 23-year-old male patient who sustained a static line injury resulting in a full-thickness tear of his biceps brachii muscle and a partial tear of the coracobrachialis muscle. OUTCOMES: The individual described in this case report reported having no functional limitations in regard to his job and leisure activities or any pain at his 6-month follow-up, with a score of 0% noted on his Shortened Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH). Isokinetic testing revealed a 39.1% decrease in elbow flexion peak torque and a 60.8% decrease in elbow flexion total work output at this same follow-up interval. DISCUSSION: In determining the appropriate course of treatment for this injury type, conservative physical therapy intervention should be considered as a viable treatment option, as there have been no decisive studies to suggest superior outcomes with other methods such as surgical correction. It is further recommended that research be conducted in an effort to prevent such injuries from occurring, as this mechanism of injury has proven to be much higher among the US military population compared with other military populations.

Sulfur K-edge spectroscopic investigation of second coordination sphere effects in oxomolybdenum-thiolates: relationship to molybdenum-cysteine covalency and electron transfer in sulfite oxidase.

Second-coordination sphere effects such as hydrogen bonding and steric constraints that provide for specific geometric configurations play a critical role in tuning the electronic structure of metalloenzyme active sites and thus have a significant effect on their catalytic efficiency. Crystallographic characterization of vertebrate and plant sulfite oxidase (SO) suggests that an average O(oxo)-Mo-S(Cys)-C dihedral angle of approximately 77 degrees exists at the active site of these enzymes. This angle is slightly more acute (approximately 72 degrees) in the bacterial sulfite dehydrogenase (SDH) from Starkeya novella. Here we report the synthesis, crystallographic, and electronic structural characterization of Tp*MoO(mba) (where Tp* = (3,5-dimethyltrispyrazol-1-yl)borate; mba = 2-mercaptobenzyl alcohol), the first oxomolybdenum monothiolate to possess an O(ax)-Mo-S(thiolate)-C dihedral angle of approximately 90 degrees . Sulfur X-ray absorption spectroscopy clearly shows that O(ax)-Mo-S(thiolate)-C dihedral angles near 90 degrees effectively eliminate covalency contributions to the Mo(xy) redox orbital from the thiolate sulfur. Sulfur K-pre-edge X-ray absorption spectroscopy intensity ratios for the spin-allowed S(1s) --> Sv(p) + Mo(xy) and S(1s) --> Sv(p) + Mo(xz,yz) transitions have been calibrated by a direct comparison of theory with experiment to yield thiolate Sv(p) orbital contributions, c(j)(2), to the Mo(xy) redox orbital and the Mo(xz,yz) orbital set. Furthermore, these intensity ratios are related to a second coordination sphere structural parameter, the O(oxo)-Mo-S(thiolate)-C dihedral angle. The relationship between Mo-S(thiolate) and Mo-S(dithiolene) covalency in oxomolydenum systems is discussed, particularly with respect to electron-transfer regeneration in SO.

Voltammetric measurements at the surface of cotton: absorption and catalase reactivity of a dinuclear manganese complex.

Voltammetric measurements at the surface of cotton fabric were conducted after impregnating the surface of the textile with graphite flakes. The resulting conducting surface contact was connected to a conventional basal plane pyrolytic graphite substrate electrode and employed both in stagnant solution and in rotating disc voltammetry mode. Diffusion through the immobilized cotton sample (inter-fiber) is probed with the aqueous Fe(CN)6(4-/3-) redox system. With a small amount of platinum immobilized at the cotton surface, catalase reactivity toward hydrogen peroxide was observed and used to further quantify the diffusion (intra- and inter-fiber) into the reactive zone at the graphite-cotton interface. A well-known catalase model system, the dinuclear manganese metal complex [Mn(IV)2(micro-O)3L2](PF6)2 (with L=1,4,7-trimethyl-1,4,7-triazacyclononane), is investigated in aqueous 0.1 M carbonate buffer at pH 9.8 in contact with cotton fabric. Absorption of the metal complex is monitored and quantified by voltammetric methods. A Langmurian binding constant of approximately K=2x103 M-1 was determined. Voltammetric measurements of the adsorbed metal complex reveal strong absorption and chemically irreversible reduction characteristics similar to those observed in solution. In the presence of hydrogen peroxide, catalyst coverage dependent anodic catalase activity was observed approximately following the rate law rate=k[catalyst]surface[H2O2]solution and with k=3x104 dm3 s-1 mol-1. The catalyst reactivity was modified by the presence of cotton.

Tridentate copper ligand influences on heme-peroxo-copper formation and properties: reduced, superoxo, and mu-peroxo iron/copper complexes.

In cytochrome c oxidase synthetic modeling studies, we recently reported a new mu-eta2:eta2-peroxo binding mode in the heteronuclear heme/copper complex [(2L)Fe(III)-(O2(2-))-CuII]+ (6) which is effected by tridentate copper chelation (J. Am. Chem. Soc. 2004, 126, 12716). To establish fundamental coordination and O2-reactivity chemistry, we have studied and describe here (i) the structure and dioxygen reactivity of the copper-free compound (2L)FeII (1), (ii) detailed spectroscopic properties of 6 in comparisons with those of known mu-eta2:eta1 heme-peroxo-copper complexes, (iii) formation of 6 from the reactions of [(2L)FeIICuI]+ (3) and dioxygen by stopped-flow kinetics, and (iv) reactivities of 6 with CO and PPh3. In the absence of copper, 1 serves as a myoglobin model compound possessing a pyridine-bound five-coordinate iron(II)-porphyrinate which undergoes reversible dioxygen binding. Oxygenation of 3 below -60 degrees C generates the heme-peroxo-copper complex 6 with strong antiferromagnetic coupling between high-spin iron(III) and copper(II) to yield an S = 2 spin system. Stopped-flow kinetics in CH2Cl2/6% EtCN show that dioxygen reacts with iron(II) first to form a heme-superoxide moiety, [(EtCN)(2L)FeIII-(O2-)...CuI(EtCN)]+ (5), which further reacts with Cu(I) to generate 6. Compared to those properties of a known mu-eta2:eta1-heme-peroxo-copper complex, 6 has a significantly diminished resonance Raman nu(O-O) stretching frequency at 747 cm(-1) and distinctive visible absorptions at 485, 541, and 572 nm, all of which seem to be characteristics of a mu-eta2:eta2-heme-peroxo-copper system. Addition of CO or PPh3 to 6 yields a bis-CO adduct of 3 or a PPh(3) adduct of 5, the latter with a remaining FeIII-(O2-) moiety.

Spectroscopy and bonding in side-on and end-on Cu2(S2) cores: comparison to peroxide analogues.

Spectroscopic methods combined with density functional calculations were used to study the disulfide-Cu(II) bonding interactions in the side-on micro -eta(2):eta(2)-bridged Cu(2)(S(2)) complex, [[Cu(II)[HB(3,5-Pr(i)(2)pz)(3)]](2)(S(2))], and the end-on trans- micro -1,2-bridged Cu(2)(S(2)) complex, [[Cu(II)(TMPA)](2)(S(2))](2+), in correlation to their peroxide structural analogues. Resonance Raman shows weaker S-S bonds and stronger Cu-S bonds in the disulfide complexes relative to the O-O and Cu-O bonds in the peroxide analogues. The weaker S-S bonds come from the more limited interaction between the S 3p orbitals relative to that of the O 2s/p hybrid orbitals. The stronger Cu-S bonds result from the more covalent Cu-disulfide interactions relative to the Cu-peroxide interactions. This is consistent with the higher energy of the disulfide valence level relative to that of the peroxide. The ground states of the side-on Cu(2)(S(2))/Cu(2)(O(2)) complexes are more covalent than those of the end-on Cu(2)(S(2))/Cu(2)(O(2)) complexes. This derives from the larger sigma-donor interactions in the side-on micro -eta(2):eta(2) structure, which has four Cu-disulfide/peroxide bonds, relative to the end-on trans- micro -1,2 structure, which forms two bonds to the Cu. The larger disulfide/peroxide sigma-donor interactions in the side-on complexes are reflected in their more intense higher energy disulfide/peroxide to Cu charge transfer transitions in the absorption spectra. The large ground-state covalencies of the side-on complexes result in significant nuclear distortions in the ligand-to-metal charge transfer excited states, which give rise to the strong resonance Raman enhancements of the metal-ligand and intraligand vibrations. Particularly, the large covalency of the Cu-disulfide interaction in the side-on Cu(2)(S(2)) complex leads to a different rR enhancement profile, relative to the peroxide analogues, reflecting a S-S bond distortion in the opposite directions in the disulfide/peroxide pi(sigma) to Cu charge transfer excited states. A ligand sigma back-bonding interaction exists only in the side-on complexes, and there is more sigma mixing in the side-on Cu(2)(S(2)) complex than in the side-on Cu(2)(O(2)) complex. This sigma back-bonding is shown to significantly weaken the S-S/O-O bond relative to that of the analogous end-on complex, leading to the low nu(S)(-)(S)/nu(O)(-)(O) vibrational frequencies observed in the resonance Raman spectra of the side-on complexes.

Nature of the oxomolybdenum-thiolate pi-bond: implications for Mo-S bonding in sulfite oxidase and xanthine oxidase.

The electronic structure of cis,trans-(L-N(2)S(2))MoO(X) (where L-N(2)S(2) = N,N'-dimethyl-N,N'-bis(2-mercaptophenyl)ethylenediamine and X = Cl, SCH(2)C(6)H(5), SC(6)H(4)-OCH(3), or SC(6)H(4)CF(3)) has been probed by electronic absorption, magnetic circular dichroism, and resonance Raman spectroscopies to determine the nature of oxomolybdenum-thiolate bonding in complexes possessing three equatorial sulfur ligands. One of the phenyl mercaptide sulfur donors of the tetradentate L-N(2)S(2) chelating ligand, denoted S(180), coordinates to molybdenum in the equatorial plane such that the OMo-S(180)-C(phenyl) dihedral angle is approximately 180 degrees, resulting in a highly covalent pi-bonding interaction between an S(180) p orbital and the molybdenum d(xy) orbital. This highly covalent bonding scheme is the origin of an intense low-energy S --> Mo d(xy) bonding-to-antibonding LMCT transition (E(max) approximately 16000 cm(-)(1), epsilon approximately 4000 M(-)(1) cm(-)(1)). Spectroscopically calibrated bonding calculations performed at the DFT level of theory reveal that S(180) contributes approximately 22% to the HOMO, which is predominantly a pi antibonding molecular orbital between Mo d(xy) and the S(180) p orbital oriented in the same plane. The second sulfur donor of the L-N(2)S(2) ligand is essentially nonbonding with Mo d(xy) due to an OMo-S-C(phenyl) dihedral angle of approximately 90 degrees. Because the formal Mo d(xy) orbital is the electroactive or redox orbital, these Mo d(xy)-S 3p interactions are important with respect to defining key covalency contributions to the reduction potential in monooxomolybdenum thiolates, including the one- and two-electron reduced forms of sulfite oxidase. Interestingly, the highly covalent Mo-S(180) pi bonding interaction observed in these complexes is analogous to the well-known Cu-S(Cys) pi bond in type 1 blue copper proteins, which display electronic absorption and resonance Raman spectra that are remarkably similar to these monooxomolybdenum thiolate complexes. Finally, the presence of a covalent Mo-S pi interaction oriented orthogonal to the MOO bond is discussed with respect to electron-transfer regeneration in sulfite oxidase and Mo=S(sulfido) bonding in xanthine oxidase.

Reaction of elemental sulfur with a copper(I) complex forming a trans-mu-1,2 end-on disulfide complex: new directions in copper-sulfur chemistry.

Elemental sulfur (S8) was found to react with [(TMPA)CuI(CH3CN)]+ to form the trans-mu-1,2 end-on disulfide complex [(TMPA)Cu-S-S-Cu(TMPA)]2+. The X-ray structure of this centrosymmetric disulfide complex shows a Cu(1)-S(1) bond length of 2.280(2) A and a S(1)-S(1A) bond length of 2.044(4) A.

Heme/Cu/O2 reactivity: change in FeIII-(O2 2-)-CuII unit peroxo binding geometry effected by tridentate copper chelation.

A new heme-peroxo-copper complex structural type with mu-eta2:eta2 peroxo ligation has been generated utilizing a heterobinucleating ligand with bis(2-(2-pyridyl)ethyl)amine tridentate chelate for copper. Oxygenation of [(2L)FeIICuI]+ (1) at -80 degrees C in CH2Cl2/6%EtCN, 1 (lambdamax, 426, 530 nm) produces [(2L)FeIII-(O22-)-CuII)]+ (3) (lambdamax, 419, 488, 544, 575 nm). Stopped-flow kinetic/spectroscopic probing reveals that a superoxo complex, [(2L)FeIII-(O2-)...CuI(NCEt)]+ (2) (lambdamax = 544 nm), initially forms, k1 = 5.23 +/- 0.09 x 104 M-1 s-1 (-105 degrees C). Subsequent intramolecular reaction of the copper(I) ion in 2 occurs with k2 = 2.74 +/- 0.04 x 101 s-1 (-105 degrees C), producing 3. Resonance Raman spectroscopy (rR) confirms the peroxo assignment for 3; nu(O-O) = 747 cm-1 (Delta(18O2) = -40 cm-1). In an 16O-18O mixed isotope experiment a single band is observed at 730 cm-1. The low nu(O-O) value and the absence of a splitting of the 730 cm-1 band are indicative of a symmetrical binding of the peroxide group in a side-on mu-eta2:eta2 geometry. This conclusion is supported by X-ray absorption spectroscopy on 3. Copper K-edge EXAFS indicates a five-coordinate metal center: 2 N, 2.028(7) A; 2 O, 1.898(7) A; 1 N, 2.171(12) A. An outer-sphere Fe scatterer is found at 3.62(1) A. The iron center K-edge EXAFS fits to either a five- or six-coordinate metal center: 4 N(pyrrole), approximately 2.1 A; 1,2 O, approximately 1.9 A. A preedge feature (Fe(1s) --> Fe(3d) transition) at 7113.2(2) eV resembles that obtained for a eta2-peroxo ferric heme complex, being weaker and at approximately 1.5 eV lower energy than those found in five-coordinate (P)FeIII-X (in C4v symmetry) complexes. Arguments based on rR properties of relevant peroxo compounds also effectively point to the copper(II) ion in 3 as being side-on bound, leading to the very low O-O stretching frequency observed in comparison to those of heme-peroxo species or heme-peroxo-copper complexes with a tetradentate copper chelate. These investigations derive from interest in establishing relevant and/or fundamental O2 chemistry at heme-copper centers, in relation to heme-copper oxidase active-site chemistry.