Quinolino[7,8-h]quinoline: a 'just right' ligand for beryllium(II) coordination.

We report the synthesis and crystal structure of the first quinolino[7,8-h]quinoline beryllium(II) complex of the general formula [BeL2(MeCN)Br]Br·MeCN, containing the ligand 4,9-dihydroxyquinolino[7,8-h]quinoline (L2). The Be(II) cation is a great size match for the dinitrogen binding pocket of the quinolino[7,8-h]quinoline ligand as indicated by minimal out-of-plane displacement and ligand distortion parameters.

Deep brain stimulation effects on verbal fluency dissociated by target and active contact location.

OBJECTIVE: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but it can also disrupt verbal fluency with significant costs to quality of life. The current study investigated how variability of bilateral active electrode coordinates along the superior/inferior, anterior/posterior, and lateral/medial axes in the subthalamic nucleus (STN) or the globus pallidus interna (GPi) contribute to changes in verbal fluency. We predicted that electrode location in the left hemisphere would be linked to changes in fluency, especially in the STN. METHODS: Forty PD participants treated with bilateral DBS targeting STN (n = 23) or GPi (n = 17) completed verbal fluency testing in their optimally treated state before and after DBS therapy. Normalized atlas coordinates from left and right active electrode positions along superior/inferior, anterior/posterior, and lateral/medial axes were used to predict changes in fluency postoperatively, separately for patients with STN and GPi targets. RESULTS: Consistent with prior studies, fluency significantly declined pre- to postsurgery (in both DBS targets). In STN-DBS patients, electrode position along the inferior to superior axis in the left STN was a significant predictor of fluency changes; relatively more superior left active electrode was associated with the largest fluency declines in STN. Electrode coordinates in right STN or GPi (left or right) did not predict fluency changes. INTERPRETATION: We discuss these findings in light of putative mechanisms and potential clinical impact.

Minimally Invasive Endoscopy for Acute Subdural Hematomas: A Report of 3 Cases.

BACKGROUND: Acute subdural hematomas (aSDHs) occur in approximately 10% to 20% of all closed head injury and represent a significant cause of morbidity and mortality in traumatic brain injury patients. Conventional craniotomy is an invasive intervention with the potential for excess blood loss and prolonged postoperative recovery time. OBJECTIVE: To evaluate the outcomes of minimally invasive endoscopy for evacuation of aSDHs in a pilot feasibility study. METHODS: We retrospectively reviewed the records of consecutive patients with aSDHs who underwent surgical treatment at our institution with minimally invasive endoscopy using the Apollo/Artemis Neuro Evacuation Device (Penumbra, Alameda, California) between April 2015 and July 2018. RESULTS: The study cohort comprised three patients. The Glasgow Coma Scale on admission was 15 for all 3 patients, median preoperative hematoma volume was 49.5 cm3 (range 44-67.8 cm3), median postoperative degree of hematoma evacuation was 88% (range 84%-89%), and median modified Rankin Scale at discharge was 1 (range 0-3). CONCLUSION: Endoscopic evacuation of aSDHs can be a safe and effective alternative to craniotomy in appropriately selected patients. Further studies are needed to refine the selection criteria for endoscopic aSDH evacuation and evaluate its long-term outcomes.

A reverse 230U/226Th radionuclide generator for targeted alpha therapy applications.

PURPOSE: Thorium-226 (half-life 30.6 m) is a radionuclide of interest for use in targeted alpha therapy applications. Due to its short half-life, 226Th must be provided through a radionuclide generator system from its parent 230U (20.8 d). Furthermore, as the half-life of 226Th is very short, it should be provided in a form that is directly amenable to use in biomedical applications. METHODS: A reverse radionuclide generator system was developed employing a DGA extraction chromatography column. A 230U/226Th parent/daughter solution in equilibrium is added to a DGA column in >6 M HCl. The parent 230U is eluted first in 0.1 M HNO3 followed by elution of 226Th in 0.1 M citrate buffer pH 5. RESULTS: Thorium-226 was recovered from the radionuclide generator column with >96% yield. Greater than 99.5% of the 230U parent was isolated for reuse in the generator. Long term evaluation over six weeks demonstrated consistent supply of 226Th with greater than 99.5% radionuclidic purity. The only contaminant found in the final product was 230U (<0.5%). CONCLUSIONS: The reverse radionuclide generator described herein was shown to be a feasible method for providing 226Th in high yield, purity and in a chemical form that is amenable for direct use in biomedical applications.

Deep Brain Stimulation Lead Implantation Using a Customized Rapidly Manufactured Stereotactic Fixture with Submillimetric Euclidean Accuracy.

BACKGROUND: The microTargetingTM MicrotableTM Platform is a novel stereotactic system that can be more rapidly fabricated than currently available 3D-printed alternatives. We present the first case series of patients who underwent deep brain stimulation (DBS) surgery guided by this platform and demonstrate its in vivo accuracy. METHODS: Ten patients underwent DBS at a single institution by the senior author and 15 leads were placed. The mean age was 69.1 years; four were female. The ventralis intermedius nucleus was targeted for patients with essential tremor and the subthalamic nucleus was targeted for patients with Parkinson's disease. RESULTS: Nine DBS leads in 6 patients were appropriately imaged to enable measurement of accuracy. The mean Euclidean electrode placement error (EPE) was 0.97 ± 0.37 mm, and the mean radial error was 0.80 ± 0.41 mm (n = 9). In the subset of CT scans performed greater than 1 month postoperatively (n = 3), the mean Euclidean EPE was 0.75 ± 0.17 mm and the mean radial error was 0.69 ± 0.17 mm. There were no surgical complications. CONCLUSION: The MicrotableTM platform is capable of submillimetric accuracy in patients undergoing stereotactic surgery. It has achieved clinical efficacy in our patients without surgical complications and has demonstrated the potential for superior accuracy compared to both traditional stereotactic frames and other common frameless systems.

Advancing Chelation Chemistry for Actinium and Other +3 f-Elements, Am, Cm, and La.

A major chemical challenge facing implementation of 225Ac in targeted alpha therapy-an emerging technology that has potential for treatment of disease-is identifying an 225Ac chelator that is compatible with in vivo applications. It is unclear how to tailor a chelator for Ac binding because Ac coordination chemistry is poorly defined. Most Ac chemistry is inferred from radiochemical experiments carried out on microscopic scales. Of the few Ac compounds that have been characterized spectroscopically, success has only been reported for simple inorganic ligands. Toward advancing understanding in Ac chelation chemistry, we have developed a method for characterizing Ac complexes that contain highly complex chelating agents using small quantities (µg) of 227Ac. We successfully characterized the chelation of Ac3+ by DOTP8- using EXAFS, NMR, and DFT techniques. To develop confidence and credibility in the Ac results, comparisons with +3 cations (Am, Cm, and La) that could be handled on the mg scale were carried out. We discovered that all M3+ cations (M = Ac, Am, Cm, La) were completely encapsulated within the binding pocket of the DOTP8- macrocycle. The computational results highlighted the stability of the M(DOTP)5- complexes.

Minimally Invasive Surgery for Spontaneous Cerebellar Hemorrhage: A Multicenter Study.

BACKGROUND: Spontaneous intracranial hemorrhage (ICH) of the cerebellum can be life threatening because of mass effect on the brainstem and fourth ventricle. Suboccipital craniectomy is currently the treatment of choice for cerebellar ICH evacuation. Minimally invasive surgery (MIS) is currently being investigated for the treatment of supratentorial ICH. However, its utility for cerebellar ICH is unknown. The aim of this multicenter, retrospective cohort study is to evaluate the outcomes of MIS for cerebellar ICH. METHODS: We retrospectively reviewed the records of all patients with cerebellar ICH who underwent MIS using either the Apollo or Artemis Neuro Evacuation Device (Penumbra Inc., Alameda, California, USA) at 3 institutions from May 2015 to July 2018. Data from each contributing center were deidentified and pooled for analysis. RESULTS: The study cohort comprised 6 patients with a median age of 62.5 years. The median pre- and postoperative Glasgow Coma Scale scores were 10.5 and 15, respectively. The median degree of hematoma evacuation was 97.5% (range, 79%-100%). There were no procedural complications, but 1 patient required subsequent craniectomy (retreatment rate 17%). The median discharge modified Rankin scale score was 4, including 3 patients who improved to functional independence at follow-up durations of 3 months. Two patients died from medical complications (mortality rate 33%). CONCLUSIONS: MIS could represent a reasonable alternative to conventional surgery for the treatment of appropriately selected patients with cerebellar ICH. However, further studies are needed to clarify the perioperative and long-term risk to benefit profiles of this technique.

Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins.

Protactinium-230 ( t1/2 = 17.4 d) is the parent isotope of 230U ( t1/2 = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT). Column chromatographic methods have been developed to separate no-carrier-added 230Pa from proton irradiated thorium targets and accompanying fission products. Results reported within demonstrate the use of novel sulfur bearing chromatographic extraction resins for the selective separation of protactinium. The recovery yield of 230Pa was 93 ± 4% employing a R3P═S type commercially available resin and 88 ± 4% employing a DGTA (diglycothioamide) containing custom synthesized extraction chromatographic resin. The radiochemical purity of the recovered 230Pa was measured via high purity germanium γ-ray spectroscopy to be >99.5% with the remaining radioactive contaminant being 95Nb due to its similar chemistry to protactinium. Measured equilibrium distribution coefficients for protactinium, thorium, uranium, niobium, radium, and actinium on both the R3P═S type and the DGTA resin in hydrochloric acid media are reported, to the best of our knowledge, for the first time.

Synthesis and radiometric evaluation of diglycolamide functionalized mesoporous silica for the chromatographic separation of actinides Th, Pa and U.

The separation of Th, Pa, and U is of high importance in many applications including nuclear power, nuclear waste, environmental and geochemistry, nuclear forensics and nuclear medicine. Diglycolamide (DGA)-based resins have shown the ability to separate many elements, however, these resins consist of non-covalent impregnation of the DGA molecules on the resin backbone resulting in co-elution of the extraction molecule during separation cycles, therefore limiting their long-term and repeated use. Covalently binding the DGA molecules onto silica is one way to overcome this issue. Herein, measured equilibrium distribution coefficients of normal extraction chromatographic DGA resin and a covalently bound form (KIT-6-N-DGA sorbent) are reported. Several differences are observed between the two systems, the most significant being observed for uranium, which demonstrated significantly lower sorption behavior on KIT-6-N-DGA. These results indicate that U can effectively be separated from Th and Pa using KIT-6-N-DGA, a task that could not be completed with the use of normal DGA alone.

Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations.

Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting. Numerous studies have demonstrated the in vitro and in vivo efficacy of the targeted α-therapy. Radium-223 (223Ra) dichloride (Xofigo®) is the first α-emitter to have received FDA approval for the treatment of prostate cancer with metastatic bone lesions. There is a significant increase in the number of clinical trials in oncology using several radionuclides such as Actinium-225 (225Ac), Bismuth-213 (213Bi), Lead-212 (212Pb), Astatine (211At) or Radium-223 (223Ra) assessing their safety and preliminary activity. This review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.

Exposing an "Intangible" Cognitive Skill among Collegiate Football Players: Enhanced Interference Control.

American football is played in a chaotic visual environment filled with relevant and distracting information. We investigated the hypothesis that collegiate football players show exceptional skill at shielding their response execution from the interfering effects of distraction (interference control). The performances of 280 football players from National Collegiate Athletic Association Division I football programs were compared to age-matched controls in a variant of the Eriksen flanker task (Eriksen and Eriksen, 1974). This task quantifies the magnitude of interference produced by visual distraction on split-second response execution. Overall, football athletes and age controls showed similar mean reaction times (RTs) and accuracy rates. However, football athletes were more proficient at shielding their response execution speed from the interfering effects of distraction (i.e., smaller flanker effect costs on RT). Offensive and defensive players showed smaller interference costs compared to controls, but defensive players showed the smallest costs. All defensive positions and one offensive position showed statistically smaller interference effects when compared directly to age controls. These data reveal a clear cognitive advantage among football athletes at executing motor responses in the face of distraction, the existence and magnitude of which vary by position. Individual differences in cognitive control may have important implications for both player selection and development to improve interference control capabilities during play.

Chromatographic separation of the theranostic radionuclide 111Ag from a proton irradiated thorium matrix.

Column chromatographic methods have been developed to separate no-carrier-added 111Ag from proton irradiated thorium targets and associated fission products as an ancillary process to an existing 225Ac separation design. Herein we report the separation of 111Ag both prior and subsequent to 225Ac recovery using CL resin, a solvent impregnated resin (SIR) that carries an organic solution of alkyl phosphine sulfides (R3P = S) and alkyl phosphine oxides (R3P = O). The recovery yield of 111Ag was 93 ± 9% with a radiochemical purity of 99.9% (prior) and 87 ± 9% with a radiochemical purity of 99.9% (subsequent to) 225Ac recovery. Both processes were successfully performed with insignificant impacts on 225Ac yields or quality. Measured equilibrium distribution coefficients for silver and ruthenium (a residual contaminant) on CL resin in hydrochloric and nitric acid media are reported, to the best of our knowledge, for the first time. Additionally, measured cross sections for the production of 111Ag and 110mAg for the 232Th(p,f)110m,111Ag reactions are reported within.

Separation of 103Ru from a proton irradiated thorium matrix: A potential source of Auger therapy radionuclide 103mRh.

Ruthenium-103 is the parent isotope of 103mRh (t1/2 56.1 min), an isotope of interest for Auger electron therapy. During the proton irradiation of thorium targets, large amounts of 103Ru are generated through proton induced fission. The development of a two part chemical separation process to isolate 103Ru in high yield and purity from a proton irradiated thorium matrix on an analytical scale is described herein. The first part employed an anion exchange column to remove cationic actinide/lanthanide impurities along with the majority of the transition metal fission products. Secondly, an extraction chromatographic column utilizing diglycolamide functional groups was used to decontaminate 103Ru from the remaining impurities. This method resulted in a final radiochemical yield of 83 ± 5% of 103Ru with a purity of 99.9%. Additionally, measured nuclear reaction cross sections for the formation of 103Ru and 106Ru via the 232Th(p,f)103,106Ru reactions are reported within.

Radiometric evaluation of diglycolamide resins for the chromatographic separation of actinium from fission product lanthanides.

Actinium-225 is a potential Targeted Alpha Therapy (TAT) isotope. It can be generated with high energy (≥ 100MeV) proton irradiation of thorium targets. The main challenge in the chemical recovery of 225Ac lies in the separation from thorium and many fission by-products most importantly radiolanthanides. We recently developed a separation strategy based on a combination of cation exchange and extraction chromatography to isolate and purify 225Ac. In this study, actinium and lanthanide equilibrium distribution coefficients and column elution behavior for both TODGA (N,N,N',N'-tetra-n-octyldiglycolamide) and TEHDGA (N,N,N',N'-tetrakis-2-ethylhexyldiglycolamide) were determined. Density functional theory (DFT) calculations were performed and were in agreement with experimental observations providing the foundation for understanding of the selectivity for Ac and lanthanides on different DGA (diglycolamide) based resins. The results of Gibbs energy (ΔGaq) calculations confirm significantly higher selectivity of DGA based resins for LnIII over AcIII in the presence of nitrate. DFT calculations and experimental results reveal that Ac chemistry cannot be predicted from lanthanide behavior under comparable circumstances.

Simultaneous Separation of Actinium and Radium Isotopes from a Proton Irradiated Thorium Matrix.

A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.

Proton-induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development.

Scandium-44g (half-life 3.97h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175MBq (4.7mCi) batch yield of 44Ti in week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 102-103. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In summary, this method yields a 90-97% 44Ti recovery with an overall Ti/Sc separation factor of ≥106.

Synthesis and Characterization of the Actinium Aquo Ion.

Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H2O) x3+) is critical for current efforts to develop 225Ac [t1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity, many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227Ac [t1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the AcIII cation with an Ac-OH2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that AcIII was coordinated by 9 water molecules with Ac-OH2O distances ranging from 2.61 to 2.76 Å. The data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large AcIII coordination numbers and long Ac-OH2O bond distances.

Bulk production and evaluation of high specific activity 186gRe for cancer therapy using enriched 186WO3 targets in a proton beam.

INTRODUCTION: Rhenium-186g (t1/2 = 3.72 d) is a ß- emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ)186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a higher specific activity, allowing it to be used more broadly for targeted radiotherapy applications. This targets the unmet clinical need for more efficient radiotherapeutics. METHODS: A target consisting of highly enriched, pressed 186WO3 was irradiated with protons at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF) to evaluate 186gRe product yield and quality. LANL-IPF was operated in a dedicated nominal 40 MeV mode. Alkaline dissolution followed by anion exchange chromatography was used to isolate 186gRe from the target material. Phantom and radiolabeling studies were conducted with the produced 186gRe activity. RESULTS: A 186gRe batch yield of 1.38 ± 0.09 MBq/µAh or 384.9 ± 27.3 MBq/C was obtained after 16.5 h in a 205 µA average/230µA maximum current proton beam. The chemical recovery yield was 93% and radiolabeling was achieved with efficiencies ranging from 60-80%. True specific activity of 186gRe at EOB was determined via ICP-AES and amounted to 0.788 ± 0.089 GBq/µg (0.146 ± 0.017 GBq/nmol), which is approximately seven times higher than the product obtained from neutron capture in a reactor. Phantom studies show similar imaging quality to the gold standard 99mTc. CONCLUSIONS: We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity 186gRe from enriched 186WO3 targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity.

Evaluation of nitrogen-rich macrocyclic ligands for the chelation of therapeutic bismuth radioisotopes.

INTRODUCTION: The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope (213)Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi(3+), however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents. METHODS: The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), were prepared by a previously reported method and investigated here for their abilities to bind Bi radioisotopes. The commercially available and commonly used ligands 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and N-[(R)-2-amino-3-(p-isothiocyanato-phenyl)propyl]-trans-(S,S)- cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid (CHX-A''-DTPA) were also explored for comparative purposes. Radio-thin-layer chromatography (TLC) was used to measure the binding kinetics and stabilities of the complexes formed. The long-lived isotope, (207)Bi (t(1/2)=32 years), was used for these studies. Density functional theory (DFT) calculations were also employed to probe the ligand interactions with Bi(3+) and the generator parent ion Ac(3+). RESULTS: In contrast to DOTA and CHX-A''-DTPA, these nitrogen-rich macrocycles selectively chelate Bi(3+) in the presence of the parent isotope Ac(3+). Among the four tested, L(py) was found to exhibit optimal Bi(3+)-binding kinetics and complex stability. L(py) complexes Bi(3+) more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT calculations corroborate the experimentally observed selectivity of these ligands for Bi(3+) over Ac(3+). CONCLUSION: Taken together, these data implicate L(py) as a valuable chelating agent for the delivery of (213)Bi. Its selectivity for Bi(3+) and rapid and stable labeling properties warrant further investigation and biological studies.

Synthesis and characterization of nitrogen-rich macrocyclic ligands and an investigation of their coordination chemistry with lanthanum(III).

Derivatives of the ligand 1,4,7,10-tetraazacyclododecane (cyclen) containing pendant N-heterocyclic donors were prepared. The heterocycles pyridine, pyridazine, pyrimidine, and pyrazine were conjugated to cyclen to give 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), respectively. The coordination chemistry of these ligands was explored using the La(3+) ion. Accordingly, complexes of the general formula [La(L)(OTf)](OTf)2, where OTf = trifluoromethanesulfonate and L = L(py) (1), L(pyd) (2), L(pyr) (3), and L(pz) (4), were synthesized and characterized by NMR spectroscopy. Crystal structures of 1 and 2 were also determined by X-ray diffraction studies, which revealed 9-coordinate capped, twisted square-antiprismatic coordination geometries for the central La(3+) ion. The conformational dynamics of 1-4 in solution were investigated by variable-temperature NMR spectroscopy. Dynamic line-shape and Eyring analyses enabled the determination of the activation parameters for the interconversion of enantiomeric forms of the complexes. Unexpectedly, the different pendant N-heterocycles of 1-4 give rise to varying values for the enthalpies and entropies of activation for this process. Density functional theory calculations were carried out to investigate the mechanism of this enantiomeric interconversion. Computed activation parameters were consistent with those experimentally determined for 1 but differed somewhat from those of 2-4.