The lingering symptoms of post-COVID-19 condition (long-COVID): a prospective cohort study.

BACKGROUND: Longer-term symptoms (long COVID) may be present in seemingly recovered patients for several months and can be debilitating. AIM: To investigate the prevalence and type of symptoms in those with a prior COVID-19 diagnosis. METHODS: This prospective, longitudinal observational study commenced in July 2020 investigating the longer-term health impacts of COVID-19. Participants were recruited via public health units and media publicity. Surveys were completed upon enrolment, and at 1, 3, 6 and 12 months. Outcome measures included incidence of activity limitations and symptoms against health and vaccination status, age and gender. RESULTS: Overall, 339 participants were recruited. At 3 months after COVID-19, 66.8% reported symptoms, and 44.8% were still experiencing symptoms at 12 months. Fatigue was most common at every point (between 53.1% and 33.1%). Pain symptoms increased in relative prevalence over time, whereas respiratory/pulmonary-type symptoms decreased substantially after 3 months. Females and younger people were more likely to experience symptoms in the early stages of long COVID (P < 0.01) and those with more comorbidities in the latter stages (P < 0.001). Vaccination showed a statistically significant protective effect against symptoms (P < 0.01-0.001). CONCLUSION: Long-term COVID-19 symptoms exist among recovered patients up to 12 months after contracting the virus. Fatigue is a primary contributor, while chronic pain became more problematic after 6 months. Vaccination was a factor in preventing long-term symptoms and aiding faster recovery from symptoms. Further work exploring additional contributors to symptom prevalence would assist in developing appropriate follow-up care.

How to reduce processing times for site-specific assessments from 29 to 5 days using a common-sense approach: it does not have to be that hard.

Researchers have reported limitations with research governance processes across Australia. This study aimed to streamline research governance processes across a local health district. Four basic principles were applied to remove non-value-adding and non-risk-mitigating processes. Average processing times were reduced from 29 to 5 days and end-user satisfaction was improved, all within the same staffing levels.

Evaluation of the geriatrician in the practice model of care for dementia assessment and management in rural Australia.

OBJECTIVES: To evaluate an integrated care program expanding the physician in the practice model into geriatrics, focussing on dementia assessment and management. DESIGN: Observational descriptive study. SETTING: The rural section of a local health district in New South Wales, Australia. PARTICIPANTS: Patients attending eight general practices, in addition to practice nurses and general practitioners. INTERVENTIONS: Self-report questionnaires completed by patients, specialist general practitioners and practice nurses. Responses to open-ended questions were analysed using content analysis. Routinely collected health data of patients who took part in the program were compared with data of patients from the same institution who did not take part in the program. MAIN OUTCOME MEASURES: A number of planned reviews, actual reviews and emergency department presentations for participating patients, self-efficacy amongst general practitioners and practice nurses, and patient satisfaction and comfort levels. RESULTS: The GIP program was well received by most patients, GPs and practice nurses. Almost 90% of patients found it easier to see the specialist at their general practice. They were less likely to have planned reviews, actual reviews and emergency department presentations than patients who did not take part in the program. GPs and practice nurses expressed increased confidence in and knowledge of dementia assessment and management. CONCLUSIONS: Dementia assessment and management programs based on the physician in the practice model may be well received in similar rural settings. Larger prospective studies are needed to further examine the relationship between programs and patients' health outcomes.

Introducing an orthopaedic trauma list to a regional hospital: Improved efficiencies and patient outcomes.

PROBLEM: The lack of dedicated theatre time for orthopaedic surgeries at a small rural hospital meant that operations were regularly performed after hours as well as on weekends. DESIGN: Retrospective observational audit. SETTING: Data were collected for 317 patients admitted for trauma surgery between August 2019 and March 2020 at Shoalhaven District Memorial Hospital, which has an orthopaedic service and acts as a referral hospital for a 4561-km2 catchment on the South Coast of New South Wales. KEY MEASURES FOR IMPROVEMENT: Decreased time to surgery, length of stay and proportion of after-hours operating. STRATEGIES FOR CHANGE: To quantify patient outcomes demonstrating effectiveness of the trauma list in theatre operations at the hospital, providing evidence for adequate provision of care at the rural location A reduction in out-of-hours operations results in a significant financial saving to the hospital, as well as increased safety to patients. EFFECTS OF CHANGE: Significantly more operations were performed before 16:00 hours as well as on a weekday. Trauma list patients have a shorter length of stay (4.82 vs 7.8 days). Patients prior to the trauma list waited on average 89 hours for surgery, whereas patients on the trauma list waited only 43 hours. LESSONS LEARNT: A dedicated, twice-weekly orthopaedic trauma list is able to significantly reduce after hours and weekend surgeries. Patients placed on the trauma list had a significantly shorter length of stay and time to surgery. We therefore recommend the usage of dedicated trauma lists at small, regional sites not just to achieve cost savings but also to improve the patient journey and keep patients closer and returning to the home sooner.

Using an under-utilised rural hospital to reduce surgical waiting lists.

Objectives This study aimed to evaluate patient outcomes from a 12-month pilot program establishing specialist surgical services in a small rural (Modified Monash Model, MM4) hospital on the south coast of NSW. Methods Suitable patients for ambulatory surgery were selected based on strict anaesthetic, surgical and social criteria. Skills shortfalls among nursing staff, usually with emergency or inpatient experience, were addressed by appropriate re-training and in-service training in scrub, scout and anaesthetic duties. An anonymous post-operative patient survey was administered during the pilot program, which assessed patient experiences and outcomes. Of 162 patients undergoing surgery during the pilot, 50 consecutive participants completed the survey. Results Of the 161 procedures during the pilot program, 100 were performed under sedation and locoregional anaesthesia and 62 under general anaesthesia. Half (n = 86, 53.4%) were complex excisions of malignant skin lesions, and of these 63% also required either a skin graft or local flap repair. Survey respondents reported adequate information and pain relief upon discharge (n = 45, 96%) and 100% were satisfied with the care received. No respondents needed to see a doctor following discharge. There were no mortality events or major issues of morbidity during the study period or subsequently, no further overnight admissions or return to theatre and no re-presentations within 48 h of operating. Two superficial surgical site infections were reported. Conclusions There is merit in drawing on underutilised resources in small rural hospitals in support of initiatives to reduce surgical waitlists. Appropriate outpatient surgeries can be safely performed with high levels of patient satisfaction.

Time is brain, so we must BEFAST: Improving stroke identification and triage in a rural emergency department.

OBJECTIVE: Shoalhaven District Memorial Hospital is a rural (MM3) secondary hospital which is over an hour travel time from the nearest tertiary centre. The objective of the present study was to pilot the implementation of the BEFAST (Balance, Eyes, Face, Arms, Speech and Time) stroke screening tool at the ED, and determine whether its usage improved timely stroke detection. METHODS: During initial implementation and training (October-December 2019), triage nurses consulted with senior medical officers before activating stroke calls. Data were collected for the subsequent 24 months (January 2020-2022), and retrospective records for confirmed strokes during a 24-month period prior to BEFAST implementation (October 2017-2019) were also collected. The main outcome measures were triage category, CT scan result time, discharge destination, length of stay (LOS) and Modified Rankin Score (MRS). RESULTS: After BEFAST implementation, patients (n = 268) were three times more likely to be triaged at category 1 or 2, and door-to-CT scan time was reduced by 20.7 min on average. More patients were discharged to their usual residence and more quickly (LOS 7.9 vs 11.1 days). MRS 90 days after stroke was less, and patients were nearly twice as likely to experience an improvement in neurological symptoms. CONCLUSIONS: Patient outcomes were improved after implementation of the BEFAST stroke triage tool. More stroke patients were identified upon presentation to the ED, and in a timely fashion. For those with a stroke diagnosis, time-critical interventions can take place earlier, allowing patients to return home sooner, and with less disability.

Adherence to therapeutic gastroscopy guidelines for acute esophageal food bolus impaction: Impact on adverse outcomes and length of stay.

Background and Aim: According to the European Society of Gastrointestinal Endoscopy (ESGE), gastroscopy should be conducted within 6 h for complete obstruction and 24 h for incomplete obstruction due to food bolus impaction. This study explores whether adults with acute esophageal food bolus (FB) impaction experience adverse outcomes when their time to esophagogastroduodenoscopy (EGD) deviates from the recommended guidelines. Methods: A retrospective review was performed on the records of 248 patients who presented at the study site between 2015 and 2022 with symptoms of FB impaction. Results: Two hundred and forty-eight patients underwent EGD for FB impaction. Grade 1 (erosion, ulceration), Grade 2 (tear), and Grade 3 (perforation) complications were present in 31.6%, 6.9%, and 0.8% of cases, respectively. Of the 134 (54.0%) patients with complete obstruction, 51 (38.1%) received EGD within the recommended 6 h. Of the 114 (46%) patients with incomplete obstructions, 93 (81.6%) received EGD within the recommended 24 h. There was no statistically significant correlation between length of stay (LOS) post-EGD and any of ingestion to presentation time, presentation to EGD time, or ingestion to EGD time. Age and complication level were greater predictors of longer LOS than presentation to EGD time. Patients who presented in hours were significantly more likely to receive EGD within the 6- and 24-h guidelines than those who presented out of hours (50.7% vs 22.0%). Conclusion: Neither time to EGD from ingestion of food bolus nor time to EGD from hospital presentation correlated with complication rate, complication severity, or length of stay post-EGD.

Evaluating soft collars in pre-hospital cervical spine immobilisation: A cohort study on neurological outcomes, patient comfort and paramedic perspectives.

OBJECTIVE: Cervical spinal immobilisation procedures often include rigid cervical collars which, despite associated complications, may provide less immobilisation than previously thought. The present study reports the incidence of worsening neurological outcomes following soft collar application, and additionally reports patient comfort, compliance with spinal immobilisation, and paramedic perspectives on usage. METHODS: This was an observational cohort study conducted in selected metropolitan and regional areas of NSW Ambulance between 1 May 2022 and 31 March 2023. Soft collars were used exclusively in place of rigid collars. The SPEED (SPinal Emergency Evaluation of Deficits) tool was used to evaluate new or worsening neurological deficits following pre-hospital soft collar application. Secondary outcomes included patient-reported comfort of the device, and paramedic assessment of efficacy. RESULTS: Overall, 2098 soft collars were applied, of which 74 patients (3.5%) were subsequently found to have a cervical spine injury. Eight patients had a spinal cord injury, of which two experienced a worsening neurological deficit after soft collar application. In both instances, comprehensive case reviews determined that this was unlikely to have been attributable to the soft collar. The majority of patients found the soft collar comfortable, and they were well-tolerated by patients who generally complied with immobility directions. Paramedics found the collar easy to apply, and felt it assisted in minimising patient movement. CONCLUSIONS: Pre-hospital use of soft collars does not appear to increase the risk of significant injury. Patients found these devices relatively comfortable, and clinicians reported overall ease of use with good patient compliance with immobility directives.

Appendicectomy pathway: Insights from electronic medical records of a local health district in Australia.

BACKGROUND: This study aims to identify the common pathways of appendicectomy, the most common emergency surgery in Australia's public hospitals and any variations within a regional public health district in New South Wales, Australia. METHODS: We analyzed the electronic medical records of 3,943 patients who underwent appendicectomy between January 2014 and July 2020 at 2 hospitals in the Illawarra Shoalhaven Local Health District, New South Wales, Australia, using the PM2 approach for surgical pathway identification and subsequent statistical analyses. RESULTS: Among 3,943 patients, 3,606 (91.5%) followed an 11-step main pathway: (1) emergency department admission, (2) surgery booking, (3) anesthesia start, (4) operating room entry, (5) surgery start, (6) surgery end, (7) anesthesia end, (8) operating room discharge, (9) postanesthesia care unit admission, (10) postanesthesia care unit discharge, and (11) hospital discharge. The median length of stay was 48.13 hours (interquartile range 32.74). The main pathway differed from either variation 1 (n = 246, 6.2%) or variation 2 (n = 30, 0.8%) only in the timing and location of anesthesia administration or conclusion. Variation 3 (n = 26, 0.7%) included patients who underwent appendicectomy twice, whereas variation 4 (n = 25, 0.6%) included patients booked for surgery before emergency department admission through community doctor referrals. Thirteen exceptional cases experienced combinations of the aforementioned pathways. The length of stay and phase durations varied between the main pathway and these variations. CONCLUSION: The appendicectomy pathway was largely standardized across the studied hospitals, with the location of anesthesia administration or conclusion affecting specific stages but not the overall length of stay. Only a complex 2-surgery pathway increased length of stay.

Emergency short stay area improves access and flow in a rural hospital.

OBJECTIVES: Shoalhaven District Memorial Hospital is a rural (MM3) 150-bed hospital in Nowra, New South Wales, whose ED has evolved to a FACEM-led model of care (MOC). It has never had an emergency short stay area (ESSA). The objective of the present study was to pilot an ESSA and determine whether this MOC would increase the operational performance of the ED. METHODS: An ESSA was designed and delivered by emergency medicine medical, nursing and allied health practitioners. The study period was July-December 2021, with a seasonally matched retrospective cohort of records extracted for comparison (July-December 2020). Both took place within the context of the ongoing COVID-19 pandemic. The primary outcome measured was percentage of admitted patients meeting Emergency Treatment Performance (ETP). Secondary outcomes included discharge ETP, overall ED and inpatient length of stay (LOS), mortality and representation rates. RESULTS: The admission ETP for patients after the implementation of the ESSA significantly increased, from 13.9% to 31.6% (χ2 = 288, P < 0.001). Discharge ETP significantly declined. There was no effect improvement on overall ETP. There was no change to mortality or representation rates. Average admission LOS decreased. CONCLUSIONS: The introduction of the ESSA significantly improved the ETP of admitted patients. Ongoing refinement of the ESSA admission processes, as well as the lifting of certain COVID-19 restrictions, could show even greater improvements in this and other areas. Ongoing research in this field is necessary, as well as a more detailed cost-benefit analysis.

An unusually flexible expanded hexaamine cage and its Cu(II) complexes: variable coordination modes and incomplete encapsulation.

The bicyclic hexaamine "cage" ligand Me(8)tricosaneN(6) (1,5,5,9,13,13,20,20-octamethyl-3,7,11,15,18,22-hexaazabicyclo[7.7.7]tricosane) is capable of encapsulating octahedral metal ions, yet its expanded cavity allows the complexed metal to adopt a variety of geometries comprising either hexadentate or pentadentate coordination of the ligand. When complexed to Cu(II) the lability of the metal results in a dynamic equilibrium in solution between hexadentate- and pentadentate-coordinated complexes of Me(8)tricosaneN(6). Both [Cu(Me(8)tricosaneN(6))](ClO(4))(2) (6-coordinate) and [Cu(Me(8)tricosaneN(6))](S(2)O(6)) (5-coordinate) have been characterized structurally. In weak acid (pH 1) a singly protonated complex [Cu(HMe(8)tricosaneN(6))](3+) has been isolated that finds the ligand binding as a pentadentate with the uncoordinated amine being protonated. vis-NIR and electron paramagnetic resonance (EPR) spectroscopy show that the predominant solution structure of [Cu(Me(8)tricosaneN(6))](2+) at neutral pH comprises a five-coordinate, square pyramidal complex. Cyclic voltammetry of the square pyramidal [Cu(Me(8)tricosaneN(6))](2+) complex reveals a reversible Cu(II/I) couple. All of these structural, spectroscopic, and electrochemical features contrast with the smaller cavity and well studied "sarcophagine" (sar, 3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane) Cu(II) complexes which are invariably hexadentate coordinated in neutral solution and cannot stabilize a Cu(I) form.

Increasing use of intraoperative cholangiogram in Australia: is it evidence-based?

BACKGROUND: The role of routine intraoperative cholangiograms (IOCs) for prevention of bile duct injury (BDI) is contentious. There are recent reports of limited utility of IOC in preventing BDI. In Australia, IOCs are used more frequently than internationally. This study aimed to evaluate the rate of IOC use in Australia and explore potential changes in practice in light of evolving evidence for the utility of IOC. METHODS: Data were collated using service item numbers in Medicare Benefits Scheme records on the Australian Government Medicare website, for services claimed between 1 January 2001 and 31 December 2019. These data were used to analyse trends in rates of IOC, cholecystectomy and BDI repair. Data were age-standardized to account for changes in the population over time. RESULTS: The number of IOCs claimed increased by 31.8% and cholecystectomies by 7.0% over the study period. Age-standardized service rates per 100 000 persons increased by 5.5 and 32.6, respectively. Rates of IOC per 100 000 cholecystectomies steadily increased across the study period, while BDI repair rates remained low and erratic. CONCLUSION: Increasing use of IOC over the last 20 years reflects a trend towards routine rather than selective IOC; however, there is little discernible change in the number of BDIs requiring repair procedures. This suggests that routine IOC use to prevent or minimize BDI is unwarranted. Further investigation is required into the selective IOC use in high-risk patients rather than mandatory use in all patients.

A new class of quadruplex DNA-binding nickel Schiff base complexes.

We have prepared six new nickel Schiff base complexes via reactions of substituted benzophenones with different diamines in the presence of nickel(ii). These new complexes were then reacted with 1-(2-choroethyl)piperidine to afford a further six novel nickel(ii) Schiff base complexes bearing pendant ethylpiperidine groups. The complexes bearing the ethylpiperidine moieties had greater solubility in water, and were therefore suitable for use in DNA binding experiments. ESI mass spectra of solutions containing 4 and the parallel, tetramolecular quadruplex Q4, contained ions attributable to formation of non-covalent complexes. In contrast, no ions from non-covalent complexes were observed when the experiments were repeated using 4 and either a double stranded DNA (dsDNA) molecule (D2), or parallel Q1, a unimolecular quadruplex DNA (qDNA). The ESI-MS binding study also revealed that 14 has a significant ability to form non-covalent complexes with qDNA, but does not interact to the same extent with D2. This is supported by the large changes to the ellipticity of bands observed in the circular dichroism spectra of two different unimolecular qDNA molecules (c-kit1 and Q1), including the latter annealed under conditions designed to induce formation of alternative topologies (antiparallel and hybrid). In Fluorescent Indicator Displacement (FID) assays conducted using the new nickel complexes, 14 gave the lowest values of DC50 for experiments conducted with Q1 and Q4. Furthermore, 14 showed greater stabilisation of an antiparallel qDNA molecule in FRET assays than when the other new complexes were examined. These results highlight the potential of 14 as a lead complex for future structure/DNA binding investigations. This is reinforced by the results obtained from cytotoxicity studies performed using four of the nickel complexes, including 14, and Chinese hamster lung cancer (V79) cells, which gave IC50 values between 4 and 12 µM. These complexes were also shown to have the ability to induce apoptosis in the same cancer cell line.

Effect of structure variations on the quadruplex DNA binding ability of nickel Schiff base complexes.

Two different series of nickel Schiff base complexes were prepared as part of a study aimed at discovering new compounds with high affinity and selectivity for quadruplex DNA (qDNA). The new complexes were prepared by modification of a literature method for synthesising N,N'-bis-(4-((1-(2-ethyl)piperidine)-oxy)salicylidene)phenylenediaminenickel(ii) (complex (1)). For Series 1 complexes, the phenylenediamine head group of the literature complex was replaced with ethylenediamine, phenanthrenediamine, R,R- and S,S-diaminocyclohexane. These complexes, as well as an asymmetric molecule featuring a naphthalene moiety on one side and a single ethyl piperidinyl salicylidene group on the other, were prepared in order to examine the effect of varying the number and position of aromatic groups on DNA binding. Series 2 complexes were isomers of those in Series 1, in which pendant ethyl piperidine groups were located at different positions. All new complexes were characterised by 1D and 2D NMR spectroscopic methods alongside microanalysis and ESI-MS. In addition, the solid state structures of eight new complexes were determined using single crystal X-ray diffraction methods. N,N'-Bis-(4-((1-(2-ethyl)piperidine)oxy)-salicylidine)diaminophenanthrenenickel(ii) (9), was shown by ESI-MS, CD spectroscopy and UV melting studies to exhibit a greater affinity towards, and ability to stabilise, dsDNA than all other complexes in the first series. ESI-MS revealed (9) to have a strong tendency to form a 1 : 1 complex with the tetramolecular, parallel qDNA molecule Q4, however it exhibited low affinity towards the parallel unimolecular qDNA molecule Q1. The enantiomeric complexes (5) and (7), featuring R,R- and S,S-diaminocyclohexane moieties, respectively, showed similar binding profiles towards all DNA molecules investigated, whereas the asymmetric complex (11), exhibited very low DNA affinity in all cases. Series 2 complexes showed very similar DNA affinity and selectivity to their isomeric counterparts in Series 1. For example, (14) and (15), both of which contain a phenylenediamine head group, showed higher affinity towards D2, Q1 and Q4, than any of the other Series 2 complexes. In addition, complex (21), which contains a meso-1,2-diphenylethylenediamine moiety, interacted strongly with Q4, but not D2 or Q1. This observation was very similar to that made previously for the isomeric complex (3).

Synthesis and characterisation of nickel Schiff base complexes containing the meso-1,2-diphenylethylenediamine moiety: selective interactions with a tetramolecular DNA quadruplex.

As part of a program of preparing metal complexes which exhibit unique affinities towards different DNA structures, we have synthesised the novel Schiff base complex N,N'-bis-4-(hydroxysalicylidine)meso-diphenylethylenediaminenickel(ii) (), via the reaction of meso-1,2-diphenylethylenediamine and 2,4-dihydroxybenzaldehyde. This compound was subsequently reacted with 1-(2-chloroethyl)piperidine or 1-(2-chloropropyl)piperidine, to afford the alkylated complexes N,N'-bis-(4-((1-(2-ethyl)piperidine)oxy)salicylidine)meso-1,2-diphenylethylenediaminenickel(ii) () and N,N'-bis-(4-((1-(3-propyl)piperidine)oxy)-salicylidine)meso-1,2-diphenylethylenediaminenickel(ii) (), respectively. These complexes were characterised by microanalysis and X-ray crystallography in the solid state, and in solution by (1)H and (13)C NMR spectroscopy. Electrospray ionisation mass spectrometry (ESI-MS) was used to confirm the identity of () and (). The affinities of () and () towards a discrete 16 mer duplex DNA molecule, and examples of both tetramolecular and unimolecular DNA quadruplexes, was explored using a variety of techniques. In addition, the affinity of two other complexes () and (), towards the same DNA molecules was examined. Complexes () and () were prepared by methods analogous to those which afforded () and (), however 1,2-phenylenediamine was used instead of meso-1,2-diphenylethylenediamine in the initial step of the synthetic procedure. The results of ESI-MS and DNA melting temperature measurements suggest that () and () exhibit a lower affinity than () and () towards the 16 mer duplex DNA molecule, while circular dichroism (CD) spectroscopy suggested that none of the four complexes had a major effect on the conformation of the nucleic acid. In contrast, ESI-MS and CD spectroscopy suggested that both () and () show significant binding to a tetramolecular DNA quadruplex. The results of ESI-MS and Fluorescence Resonance Energy Transfer (FRET) assays indicated that () and () did not bind as tightly to a unimolecular DNA quadruplex, although both complexes had a major effect on the CD spectrum of the latter. These results highlight that the presence of the meso-1,2-diphenylethylenediamine moiety in metal complexes of this type may provide a general method for instilling selectivity for some DNA quadruplexes over dsDNA.

Does cytotoxicity of metallointercalators correlate with cellular uptake or DNA affinity?

The cytotoxicity of the metallointercalators, [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1R,2R-diaminocyclohexane)](2+) ([56MERR]) and [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1S,2S-diaminocyclohexane)](2+) ([56MESS]), towards A549 human lung cancer cells was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) value obtained following exposure of A549 cells to [56MESS] for 4 h was approximately three times smaller than that obtained when [56MERR] was administered under the same conditions, indicating that the former complex displayed greater cytotoxicity. Both IC(50) values were greater than that obtained after exposure of A549 cells to cisplatin, demonstrating that the latter compound was the most cytotoxic of the three examined. Microprobe synchrotron radiation X-ray fluorescence (SR-XRF) analyses of metallointercalator-treated A549 cells showed that platinum became localised in DNA-rich regions of the nucleus. In contrast, when the same cells were treated with cisplatin the metal became distributed throughout the cell. Determination of the maximum concentration of platinum present inside the cells using graphite furnace atomic absorption spectrophotometry (GFAAS) of platinum-treated cells suggested that there was greater uptake of [56MERR] compared to [56MESS] by the A549 cells, and that platinum uptake did not account for the greater toxicity of [56MESS], as assessed by the MTT assay. Electrospray ionization mass spectrometric (ESI-MS) and circular dichroism (CD) spectroscopic studies of solutions containing either [56MERR] or [56MESS], and a duplex hexadecamer molecule, showed the two metallointercalators displayed very similar affinity towards the nucleic acid. Overall these results indicate that the difference in cytotoxicity of the two platinum metallointercalators is probably the result of variations in their interactions with other cellular components.

A comparison of the binding of metal complexes to duplex and quadruplex DNA.

Electrospray ionisation mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy were used to compare the binding of mononuclear nickel, ruthenium and platinum complexes to double stranded DNA (dsDNA) and quadruplex DNA (qDNA). CD studies provided evidence for the binding of intact complexes of all three metal ions to qDNA. ESI mass spectra of solutions containing platinum or ruthenium complexes and qDNA showed evidence for the formation of non-covalent complexes consisting of intact metal molecules bound to DNA. However, the corresponding spectra of solutions containing nickel complexes principally contained ions consisting of fragments of the initial nickel molecule bound to qDNA. In contrast ESI mass spectra of solutions containing nickel, ruthenium or platinum complexes and dsDNA only showed the presence of ions attributable to intact metal molecules bound to DNA. The fragmentation observed in mass spectral studies of solutions containing nickel complexes and qDNA is attributable to the lower thermodynamic stability of the former metal complexes relative to those containing platinum or ruthenium, as well as the slightly harsher instrumental conditions required to obtain spectra of qDNA. This conclusion is supported by the results of tandem mass spectral studies, which showed that ions consisting of intact nickel complexes bound to qDNA readily undergo fragmentation by loss of one of the ligands initially bound to the metal. The ESI-MS results also demonstrate that the binding affinity of each of the platinum and ruthenium complexes towards qDNA is significantly less than that towards dsDNA.