Staging and classification of CKD.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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\r\n\tNowadays marine propulsion systems, based on thermal machines operating under the diesel cycle, have positioned themselves as one of the main options for this type of applications. Their main comparative advantages, compared to other propulsion systems, based on thermal machines, are the low specific fuel consumption and their higher thermal efficiency. However, its main disadvantage lies in the emissions produced by combustion, such as carbon dioxide (CO2), oxide sulphur (SOx) and oxide nitrogen (NOx).
\r\n\r\n\tOver the last decade, the International Maritime Organization (IMO), has adopted a series of regulations to reduce these emissions, based on the introduction of several energy efficiency design and operational indicators for new and existing vessels.
\r\n\r\n\tIn this context, this book will focus on design and operation efficiency of ships throughout an analysis of the main propulsion systems. Starting from the use of alternative alternative fuels, to the integration of hybrid and full electric propulsion systems.
",isbn:"978-1-83969-473-8",printIsbn:"978-1-83969-472-1",pdfIsbn:"978-1-83969-474-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"579a9da63aca2172c0f0584328ae91c1",bookSignature:"Dr. Carlos Alberto Reusser",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10810.jpg",keywords:"Energy Efficiency Design Index (EEDI), Energy Efficiency Operational Indicator (EEOI), Power Take-In-Off Applications, Propulsion Systems Hybridization, Fuel Cell Applications, Multiphase Machines, Permanent Magnet Synchronous Machines, High-Efficiency Induction Machines, Power Converters for Electric Drives, Control of Hybrid Propulsion Systems, Methanol, Biofuels",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 10th 2021",dateEndSecondStepPublish:"March 10th 2021",dateEndThirdStepPublish:"May 9th 2021",dateEndFourthStepPublish:"July 28th 2021",dateEndFifthStepPublish:"September 26th 2021",remainingDaysToSecondStep:"9 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Reusser implemented an energy efficiency control strategy for the reduction in GHG emissions on the operation of marine vessels and developed several new power converter topologies for its use in marine and renewable energy applications.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"209816",title:"Dr.",name:"Carlos",middleName:"Alberto",surname:"Reusser",slug:"carlos-reusser",fullName:"Carlos Reusser",profilePictureURL:"https://mts.intechopen.com/storage/users/209816/images/system/209816.jpg",biography:"Carlos A. Reusser earned the B.Eng. degree in Naval Electrical Engineering from the Naval Polytechnic Academy in 2001, and served in the Chilean Navy for 20 years. He received the Masters in Asset Management, M.Sc. and Ph.D. degrees in Power Electronics from Universidad Tecnica Federico Santa Maria, in 2010, 2014 and 2020 respectively. From 2011-2019, was a lecturer in APOLINAV and in 2015 he became a lecturer at Universidad Tecnica Federico Santa Maria. In 2020 became Associate Professor at Pontificia Universidad Catolica de Valparaiso. His main research interests include: Electric Ship applications, Sensorless Control of Drives, Power Converters and Renewable Energies.",institutionString:"Pontificial Catholic University of Valparaiso",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Pontificial Catholic University of Valparaiso",institutionURL:null,country:{name:"Chile"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"346794",firstName:"Mia",lastName:"Miskulin",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/346794/images/15795_n.png",email:"mia@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Not only because of the frequent association between the two entities, but also because of the aggregate risk when both conditions are present in the same individual.
Despite the high prevalence, few studies are dedicated to studying CAD specifically in individuals with CKD. In fact, CKD, especially in its final stages, is a common exclusion criterion in large studies. This fact resulted in a gap in the evidence for the management of CAD, which, sometimes, results in undertreatment of CKD patients.
This chapter aims to explore the association between CAD and CKD, approaching from pathophysiology to available evidence for the treatment of these conditions.
Another scenario where there is a profound interaction between renal failure and the cardiovascular system is with regard to coronary atherosclerosis. It is known that chronic kidney disease adds risk to coronary events. The relationship between renal disease and cardiovascular mortality can be found even in the early stages of disease [1] and increases as kidney function deteriorates [2] (see Table 1 for the stages of CKD according to the National Kidney Foundation KDOQI Clinical Practice Guidelines [3]). It is also known that the population with CAD and CKD has higher mortality regardless of the treatment used for coronary disease [4].
Stages | GFR (mL/min/1.73 m2) | CKD |
---|---|---|
0 | >90 | Risk group for CKD. Absence of renal injury |
1 | >90 | Normal renal function. Presence of kidney damage |
2 | 89–60 | Discrete or functional CKD |
3 | 59–30 | Moderate or laboratory CKD |
4 | 29–15 | Severe or clinical CKD |
5 | <15 | Terminal or pre-dialytic CKD |
Staging and classification of CKD.
Several epidemiological studies have demonstrated that CKD is an independent risk factor for cardiovascular events.
The Framingham Heart Study was one of the first to associate chronic kidney disease with cardiovascular events in the general population. Of the 6233 study participants, stage 2 CKD was found in 246 men and 270 women. Of these, 81% were not diagnosed with cardiovascular disease at the start of the study. After 15 years of follow-up, there was a tendency for a higher incidence of cardiovascular events in the male population with stage 2 CKD [5]. Data from the Atherosclerosis Risk in the Communities study also confirm an increase in the risk of cardiovascular events in this same population [6]. When GFR is considered as a continuous variable, this study points to a 5–6% increase in cardiovascular risk for each loss of 10 mL/min/1.73 m2 of GFR. Go and colleagues also demonstrated, in a cohort study of 1,120,295 patients, comprised of approximately 9.6% of diabetics and 6.3% of CAD patients, a risk of death of about 1.2 times higher associated with an GFR 45–59 mL/min/1.73 m2 when compared to those with GFR ≥60 mL/min/1.73 m2 [7]. There was a growing risk as the lowest GFR was considered, culminating with a relative risk of about 5.9 in those patients with RFG <15 mL/min/1.73 m2.
There is also a worse prognosis associated with renal failure in populations with established heart disease. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) looks at the influence of GFR, even in its early stages, in a population at high risk for cardiovascular events [8]. This study accompanied patients after acute myocardial infarction complicated by systolic ventricular dysfunction or symptoms of congestive heart failure (CHF) who were randomized to either valsartan, captopril or both. After adjusting for the received treatment and comorbidities, a risk of 1.14 times greater risk for cardiovascular death was found in patients with an GFR of 60–74 mL/min/1.73 m2 (95% CI 1.02–1.27) and 1.10 times for combined events (cardiac mortality, re-infarction, CHF and stroke) when compared to the population with normal renal function. A factor that may have contributed to these findings is that the CKD population was undertreated when compared to the population with normal renal function, receiving invasive stratification (27.5% vs. 34.7%) and beta-blockers (71.9% vs. 74.7%) to a lesser extent than those with preserved renal function.
As previously described, kidney disease, even in its early stages, poses an increased risk of cardiovascular events. Even initial lesions such as a discrete fall in GFR or microalbuminuria (including patients with normal GFR) are associated with increased cardiac mortality, AMI or stroke. The main pathophysiological mechanism involved in this complex relationship appears to be endothelial dysfunction.
Endothelial dysfunction is one of the initial events of the so-called atherosclerotic gait. It is present in both small and large vessels. Reducing the bioavailability of nitric oxide (NO) is one of the main mechanisms involved in endothelial dysfunction in patients with GFR. In this context, it is important to highlight the role of asymmetric dimethyl arginine (ADMA), which is derived from protein catabolism and competitive inhibitor of NO synthase produced mainly in the endothelium, the heart and the smooth cells and is clarified by the kidneys. When in high concentrations, as in individuals with GFR, it blocks the entry of L-arginine at the cellular level, leading to a reduction in NO synthesis. This leads to increased peripheral vascular resistance, intimal hyperplasia of the vessels and consequent increase in blood pressure with remodeling of the same. Recent studies have pointed to ADMA as an independent marker of cardiovascular risk in individuals with CAD [9].
The correlation between macroalbuminuria and microalbuminuria with endothelial dysfunction measured in peripheral vessels is something that has been demonstrated and is a consequence of glomerular hyperfiltration. Thus, albuminuria has been identified not only as a consequence of the renal aggression that precedes the fall of GFR, but also as powerful marker of cardiovascular risk. Like GFR, albuminuria increases cardiovascular risk even at minimal levels. This risk increases as the albuminuria level rises, defined as normal albumin excretion (<30 mg/g), to microalbuminuria (30–300 mg/g) and, finally, with macroalbuminuria (>300 mg/g).
Several studies have demonstrated the role of albuminuria as a marker of cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial (IDNT) studied 1715 subjects with type 2 DM, hypertension and macroalbuminuria, randomizing them to receive irbesartan, amlodipine or placebo. In a post-hoc analysis of Anavekar [10], univariate analysis showed an increase in cardiovascular risk proportional to the value of albuminuria. Multivariate analysis confirmed albuminuria as an independent risk factor. The (Reduction of End Points in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) study [11] showed similar results, demonstrating a 1.92-fold higher risk of cardiovascular events in the group with albuminuria >3000 mg/g when compared to the dose group <1500 mg/g. The HOPE [12] study got a RR of 1.83 for cardiac death and 1.61 for the combined outcome of AMI or stroke in the population with albuminuria >17.7 mg/g. In addition, subsequent analyzes of HOPE suggest that albuminuria as low as 4.4 mg/g already translates into increased cardiovascular risk, suggesting that it behaves as a continuous variable [13].
Hypertension is present in most patients with CKD and atherosclerotic disease. The activation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system and sodium retention plays an important role in the development of hypertension. Recently, renalase, a regulator of cardiac function and blood pressure produced by the kidney, has been discovered. This regulator metabolizes catecholamines and has hypotensive action. Its absence may be responsible for adrenergic hyperreactivity leading to endothelial dysfunction and cardiac and vascular remodeling [9].
The activation of RAAS occurs in several ways in kidney disease. Angiotensin II stimulates NAD (P) H oxidase, leading to superoxide anion formation and contributing to endothelial dysfunction and cardiac remodeling. In addition, when angiotensin II stimulates the AT 1 receptor, there is generation of reactive oxygen species (ROS) with release of inflammatory mediators, including cytokines, adhesion molecules, PAI-1 (plasminogen activator inhibitor-1), among others. These events eventually promote the progression of atherosclerosis.
Atherosclerosis has been considered as an inflammatory condition. CKD patients are known as ‘inflamed patients’ since we have evidence of measurable inflammatory markers such as C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), factor VIIc, factor VIIIc, plasmin-antiplasmin complex, D-dimer, E-selectin, VCAM-1 and ICAM1, as well as the deleterious effects of the inflammatory process in this population [9]. The poor nutrition of these patients, evidenced by low levels of albumin, pre-albumin and transferrin, has been suggested as a possible mechanism of activation of the inflammatory process. In addition, oxidative stress, the accumulation of modified molecules after synthesis, nonenzymatic glycosylation products or other products normally cleansed by the kidney also have their role in triggering inflammation [9]. Consequently, we have alterations in the endothelium and lipoproteins leading to accelerated atherosclerosis.
CRP has been particularly studied in the chronic kidney population, being found at higher levels in the terminal CKD population than in the normal population. CRP has been shown to be an excellent marker of cardiovascular risk in this population [14, 15].
The inflammation also seems to be related to the vascular calcification process, so common in patients with CKD, markedly in those in advanced stages of the disease. Calcification may be present in the medial layer of vessels, smooth muscle cells, medial muscular arteries and valvular system. As calcification progress, the capacitance of the arterial vessels is reduced, promoting the progression of systemic arterial hypertension (SAH) and left ventricular hypertrophy (LVH). The mechanisms involved in the CKD calcification process are complex and include the passive precipitation of Ca and P in the presence of high concentrations of these ions in the extracellular, in addition to the effect of inducers of osteogenic transformation, formation of hydroxyapatite and deficiency of calcification inhibitors such as osteoprotegerin and fetuin-A. In addition, high levels of leptin, common in patients with CKD due to reduced GFR, can induce calcification via hypothalamic receptors, stimulating osteoblastic beta-adrenergic receptors, generating ROS and inducing bone morphogenetic protein-2 (BMP-2). BMPs are regulators of bone formation, acting on receptors (BMPRs) that modulate gene expression. BMP-2 and BMP-4 are promoters of calcification, while BMP-7 behaves as an inhibitor of this process. BMP-7 is expressed mainly in the kidney and its reduction is proportional to the loss of renal function (Figure 1) [9].
Atherosclerosis and calcification in renal failure. Extracted from Mizobuchi et al. [35].
The incidence of coronary disease in the CKD population is high. Gowdak and colleagues observed a 47% incidence of angiographically significant CAD among patients with terminal CKD awaiting renal transplantation [16]. Interestingly, even in the population without traditional risk factors (SAH, DM, obesity, dyslipidemia and smoking), the observed incidence of CAD was 26%, and may reach 100% among those with all risk factors mentioned above.
The best method to investigate or stratify CAD in this population is still a matter of dispute. The presence of endothelial dysfunction, LVH, hypertension and volume overload in chronic renal patients should be considered when choosing the best method.
Some studies have considered that a more aggressive strategy should be used, since the noninvasive methods do not have good accuracy in the prediction of events in this population, especially in those with terminal CKD. In an attempt to validate a strategy for diagnosis of significant CAD in a population of chronic dialysis patients, a study conducted at the Heart Institute of the Hospital das Clínicas of the USP Medical School (InCor-HCFMUSP) confirms that the documented coronary angiography and the presence of DM were good predictors of cardiovascular events. The sensitivity, specificity and positive and negative predictive values of myocardial scintigraphy with dipyridamole were 70, 74, 69 and 71%, respectively. It is worth noting that scintigraphy did not diagnose CAD in a significant number of patients with CAD confirmed by coronary angiography [16, 17]. These data confirm that the invasive strategy remains the gold standard in the diagnosis and stratification of risk in this population. It is important to remember that the use of iodinated contrast (especially in the population with discrete to moderate CRF) may worsen the renal function of these individuals, and the need for hemodialysis in cases of contrast-induced nephropathy is not uncommon. This, in addition to being an invasive, more expensive and less available method, does not authorize us to indicate routine coronary angiography for patients with CKD in the investigation and/or stratification of CAD. Clinical judgment should weigh the risk factors already mentioned to select the population that will benefit most from the invasive examination.
The use of new methods for the diagnosis of CAD, such as coronary angiotomography, calcium score and magnetic resonance imaging has also been studied in this population. In a recently published study, the calcium score applied to a population of renal transplant candidates had a good correlation with angiographic CAD for diagnosis, as well as being a good predictor of cardiovascular events when above 400 Agatston [18]. Magnetic resonance imaging has its importance mainly in the evaluation of previous infarctions, ischemia and myocardial viability in this population [19].
Treatment of coronary disease is based on optimized medical therapy associated or not with interventional procedures (surgical revascularization or angioplasty). The population with CAD and CKD has peculiarities that should not be forgotten when choosing the best therapeutic strategy.
The population of chronic renal failure with CAD is certainly a subgroup that benefits as much as possible from full clinical management because it is a group of patients with multiple comorbidities and an accelerated atherosclerosis [20]. In spite of this recommendation, the population with renal dysfunction is frequently undertreated, which surely contributes to the worse prognosis of this special population [21].
Interventional therapy in patients with chronic kidney disease with CAD seems to be beneficial in some situations, especially when we consider their high atherosclerotic load and angiographic complexity.
A retrospective study by Reddan, conducted at Duke University, analyzed 4584 patients with CAD who underwent clinical treatment, percutaneous coronary intervention (PCI) or myocardial revascularization (CABG), who were stratified according to GFR, followed and evaluated for cardiovascular events. In this study, a benefit of percutaneous treatment over clinical treatment was observed in the population with mild to moderate CRF, but not among those with terminal CKD. When comparing myocardial revascularization surgery with medical treatment, we observed that, curiously, the benefit of surgery is greater as the severity of renal failure progresses [4].
In our setting stands out a subanalysis of MASS II [22], conducted by Lopes and collaborators at InCor - HCFMUSP. In this publication, 611 patients from the original study, randomized to medical treatment, PCI or CABG, were stratified by GFR in 3 categories (RFG ≥ 90, between 89 and 60 or between 59 and 30 mL/min/1.73 m2) and classified as with normal renal function (n = 112/18%), mild (n = 349/57%) or moderate (n = 150/25%), respectively. The results point to a higher mortality among the population with moderate CRF, compared to the other two groups. In addition, it was observed that among patients with mild CRF, patients submitted to surgery had a higher survival rate free of cardiovascular events and lower mortality in 5 years compared to the population submitted to angioplasty or in exclusive medical treatment.
Lima and collaborators evaluated in a registry-type study 763 diabetic patients with CAD of the MASS group stratified according to renal function and followed for about 5 years. Of note is the high rate of CKD patients when applied clearance estimated by Cockcroft-Gault, with almost 65% of patients with some degree of CKD having clearance <90 mL/min. Even in an exclusively diabetic population, the presence of CKD was associated with higher mortality regardless of the treatment received, with survival rates of 91.1%, 89.6% and 76.2% for the preserved function, mild and moderate CKD, respectively (p = 0.001). When compared to the drug treatment, the surgical treatment was associated with lower combined event rates in the stratum with discrete CKD (86.2% versus 65.7% for CABG and TM respectively, p < 0.001) and additional revascularization in all function strata studied.
This is a population where, despite the interventional therapy chosen, there is a higher risk of morbidity and mortality when compared to the general population. A patient undergoing CABG has a 4.4-fold greater risk of in-hospital death, a 3.1-fold increase in mediastinitis, and a 2.6-fold increase in stroke than a nondialysis patient. Some studies point to the safety of angioplasty in this population, especially in single-vessel patients [23]. However, when we compare angioplasty with surgical revascularization, it seems to bring greater cardiovascular protection to these patients [24]. This can be attributed to a higher rate of restenosis in this population, which is derived from a close association with diabetes mellitus, accelerated atherosclerosis and vascular calcification [25].
Several studies in chronic coronary disease have evaluated the performance of the subpopulation of chronic renal patients in their trials. In a post-hoc analysis of the ARTS study [26], 142 patients with moderate CKD with multiarterial CAD were randomized to receive surgery or angioplasty and followed for 5 years. Regardless of the revascularization method chosen, patients with moderate CRF had more cardiovascular events (death, stroke, nonfatal AMI or additional revascularization) than the population with mild or normal renal function. When we compared the strategies, we observed that there was no significant difference in mortality (RR: 1.18, 95% CI: 0.51–2.72, p = 0.81), but a greater number of events combined in the angioplasty group (RR: 1.56, 95% CI: 1.03–2.37, p = 0.04), mainly due to additional revascularizations (29% vs. 9.6% p = 0.005).
The BARI study [27] evaluated 3608 patients (randomized and from the registry), stratifying them into two groups: with and without CRF, which was defined as baseline serum creatinine greater than 1.5 mg/dL. Of the total, 1517 patients were submitted to surgery and 2091 to angioplasty. Of these, 76 patients were considered to have chronic renal failure. This population was older and had a higher proportion of hypertensive and diabetic patients. Among patients undergoing PCI, chronic kidney disease had a higher incidence of in-hospital mortality and cardiogenic shock. In addition, this population was more susceptible to the presence of angina, hospitalizations due to cardiac reasons and less time for additional revascularization compared to the normal population. In 7 years, the population with CKD had a higher incidence of general (RR: 2.2, p < 0.001) and heart (RR: 2.8, p < 0.001) than the population with normal renal function.
Although we consider the benefit of pharmacological stents on conventional stents with regard to the lower incidence of restenosis, recent studies comparing pharmacological stents with CABG in this population show a greater benefit of the latter, especially at the expense of lower rate of additional revascularization [28]. A recent study by Marui and colleagues from the CREDO-Kyoto registry demonstrated that in 388 patients with dialytic CKD, similar incidences of general and cardiac death were observed when CABG compared with PCI in a long-term follow-up. The latter strategy, however, was associated with higher rates of AMI and additional revascularization [29].
In the post-hoc analysis of the FREEDOM study [30], comparison of interventional strategies among diabetic patients with CAD in the presence of renal dysfunction defined by estimated clearance <60 mL/min did not demonstrate superiority of CABG on PCI with first-generation pharmacological stent at MACCE rate at 5-year follow-up.
Charytan et al. [31] in a collaborative study including 10 randomized prospective studies of 3993 subjects demonstrated similar survival rates at 5 years when patients with CKD class 3–5 underwent CABG or PCI (HR 0.99, CI 0.67–1.46). However, AMI-free survival among patients with CKD class 3–5 was higher among those undergoing surgical treatment (HR: 0.49; CI: 0.29–0.82). Consistent with other studies, CABG was associated with lower rates of additional revascularization than PCI, regardless of the renal function stratum considered.
Recently, a meta-analysis by Bundhun’s et al. [32] included 18 studies involving a larger number of patients (n = 69,456, 29,239 underwent CABG and 40,217 underwent PCI). This present analysis observed a benefit of CABG in reducing mortality when compared to PCI in long-term follow-up only (OR: 0.81, 95% CI: 0.70–0.94, p = 0.007 for nondialytic, OR: 0.81, 95% CI: 0.69–096, P = 0.01 for dialytic). It is also worth mentioning a benefit in reducing additional revascularizations among those submitted to CABG in almost all studies that included this outcome. Of note, however, is the heterogeneity of the included studies, with different definitions for CKD, in addition to follow-up times ranging from 1 month to 8 years.
Off-pump CABG was also evaluated in some studies because of the theoretical benefit of a less aggressive procedure than on-pump CABG. These studies have demonstrated a lower need for blood products and dialysis in the postoperative period, shorter hospital stay in intensive care and mechanical ventilation, but with no difference in mortality in the medium term [24, 33]. Consistent with these previous results, recently published data from the Coronary Artery Bypass Grafting Surgery Off-pump Revascularization Study, comparing on-pump versus off-pump CABG, showed a reduced risk of perioperative acute renal injury associated with off-pump CABG. In spite of this, no renal protection was observed at the 1-year follow-up associated with this surgical strategy [34].
CKD has a negative impact on the prognosis of individuals with CAD regardless of the treatment. There are no peculiarities in the indication of revascularization in this population, and attention must be paid to the greater clinical and angiographic severity of this population. The drug treatment should be applied considering the potential limitations of the use of some classes among those with terminal CKD, however, avoiding at all costs under-treatment. There is still no consensus on the best therapeutic strategy for CAD (e.g. interventional versus conservative; PCI versus CABG) for those with CKD. The studies are heterogeneous and almost completeness formed by observational records, post-hoc analyses of large trials or meta-analyses. In spite of this, some clarity seems to emerge from these publications: (1) the greater the angiographic severity/severity of CKD, the greater is the benefit of surgical revascularization; (2) in the subpopulations with discrete/moderate CKD, there is no clear evidence of surgery on the other treatments; and (3) surgery is associated with less need for additional revascularization independently of the status of renal function, which suggests that this benefit is associated with the revascularization method itself, rather than the patient’s renal status.
We await the results of the ISCHEMIA-CKD study (
Stability constant of the formation of metal complexes is used to measure interaction strength of reagents. From this process, metal ion and ligand interaction formed the two types of metal complexes; one is supramolecular complexes known as host-guest complexes [1] and the other is anion-containing complexes. In the solution it provides and calculates the required information about the concentration of metal complexes.
Solubility, light, absorption conductance, partitioning behavior, conductance, and chemical reactivity are the complex characteristics which are different from their components. It is determined by various numerical and graphical methods which calculate the equilibrium constants. This is based on or related to a quantity, and this is called the complex formation function.
During the displacement process at the time of metal complex formation, some ions disappear and form a bonding between metal ions and ligands. It may be considered due to displacement of a proton from a ligand species or ions or molecules causing a drop in the pH values of the solution [2]. Irving and Rossotti developed a technique for the calculation of stability constant, and it is called potentiometric technique.
To determine the stability constant, Bjerrum has used a very simple method, and that is metal salt solubility method. For the studies of a larger different variety of polycarboxylic acid-, oxime-, phenol-containing metal complexes, Martel and Calvin used the potentiometric technique for calculating the stability constant. Those ligands [3, 4] which are uncharged are also examined, and their stability constant calculations are determined by the limitations inherent in the ligand solubility method. The limitations of the metal salt solubility method and the result of solubility methods are compared with this. M-L, MLM, and (M3) L are some types of examples of metal-ligand bonding. One thing is common, and that is these entire types metal complexes all have one ligand.
The solubility method can only usefully be applied to studies of such complexes, and it is best applied for ML; in such types of system, only ML is formed. Jacqueline Gonzalez and his co-worker propose to explore the coordination chemistry of calcium complexes. Jacqueline and et al. followed this technique for evaluate the as partial model of the manganese-calcium cluster and spectrophotometric studies of metal complexes, i.e., they were carried calcium(II)-1,4-butanediamine in acetonitrile and calcium(II)-1,2-ethylendiamine, calcium(II)-1,3-propanediamine by them.
Spectrophotometric programming of HypSpec and received data allows the determination of the formation of solubility constants. The logarithmic values, log β110 = 5.25 for calcium(II)-1,3-propanediamine, log β110 = 4.072 for calcium(II)-1,4-butanediamine, and log β110 = 4.69 for calcium(II)-1,2-ethylendiamine, are obtained for the formation constants [5]. The structure of Cimetidine and histamine H2-receptor is a chelating agent. Syed Ahmad Tirmizi has examined Ni(II) cimetidine complex spectrophotometrically and found an absorption peak maximum of 622 nm with respect to different temperatures.
Syed Ahmad Tirmizi have been used to taken 1:2 ratio of metal and cimetidine compound for the formation of metal complex and this satisfied by molar ratio data. The data, 1.40–2.4 × 108, was calculated using the continuous variation method and stability constant at room temperature, and by using the mole ratio method, this value at 40°C was 1.24–2.4 × 108. In the formation of lead(II) metal complexes with 1-(aminomethyl) cyclohexene, Thanavelan et al. found the formation of their binary and ternary complexes. Glycine,
Using the stability constant method, these ternary complexes were found out, and using the parameters such as Δ log K and log X, these ternary complex data were compared with binary complex. The potentiometric technique at room temperature (25°C) was used in the investigation of some binary complex formations by Abdelatty Mohamed Radalla. These binary complexes are formed with 3D transition metal ions like Cu2+, Ni2+, Co2+, and Zn2+ and gallic acid’s importance as a ligand and 0.10 mol dm−3 of NaNO3. Such types of aliphatic dicarboxylic acids are very important biologically. Many acid-base characters and the nature of using metal complexes have been investigated and discussed time to time by researchers [7].
The above acids (gallic and aliphatic dicarboxylic acid) were taken to determine the acidity constants. For the purpose of determining the stability constant, binary and ternary complexes were carried in the aqueous medium using the experimental conditions as stated above. The potentiometric pH-metric titration curves are inferred for the binary complexes and ternary complexes at different ratios, and formation of ternary metal complex formation was in a stepwise manner that provided an easy way to calculate stability constants for the formation of metal complexes.
The values of Δ log K, percentage of relative stabilization (% R. S.), and log X were evaluated and discussed. Now it provides the outline about the various complex species for the formation of different solvents, and using the concentration distribution, these complexes were evaluated and discussed. The conductivity measurements have ascertained for the mode of ternary chelating complexes.
A study by Kathrina and Pekar suggests that pH plays an important role in the formation of metal complexes. When epigallocatechin gallate and gallic acid combine with copper(II) to form metal complexes, the pH changes its speculation. We have been able to determine its pH in frozen and fluid state with the help of multifrequency EPR spectroscopy [8]. With the help of this spectroscopy, it is able to detect that each polyphenol exhibits the formation of three different mononuclear species. If the pH ranges 4–8 for di- or polymeric complex of Cu(II), then it conjectures such metal complexes. It is only at alkaline pH values.
The line width in fluid solutions by molecular motion exhibits an incomplete average of the parameters of anisotropy spin Hamilton. If the complexes are different, then their rotational correlation times for this also vary. The analysis of the LyCEP anisotropy of the fluid solution spectra is performed using the parameters determined by the simulation of the rigid boundary spectra. Its result suggests that pH increases its value by affecting its molecular mass. It is a polyphenol ligand complex with copper, showing the coordination of an increasing number of its molecules or increasing participation of polyphenol dimers used as ligands in the copper coordination region.
The study by Vishenkova and his co-worker [8] provides the investigation of electrochemical properties of triphenylmethane dyes using a voltammetric method with constant-current potential sweep. Malachite green (MG) and basic fuchsin (BF) have been chosen as representatives of the triphenylmethane dyes [9]. The electrochemical behavior of MG and BF on the surface of a mercury film electrode depending on pH, the nature of background electrolyte, and scan rate of potential sweep has been investigated.
Using a voltammetric method with a constant-current potential sweep examines the electrical properties of triphenylmethane dye. In order to find out the solution of MG and BF, certain registration conditions have been prescribed for it, which have proved to be quite useful. The reduction peak for the currents of MG and BF has demonstrated that it increases linearly with respect to their concentration as 9.0 × 10−5–7.0 × 10−3 mol/dm3 for MG and 6.0 × 10−5–8.0 × 10−3 mol/dm3 for BF and correlation coefficients of these values are 0.9987 for MG and 0.9961 for BF [10].
5.0 × 10−5 and 2.0 × 10−5 mol/dm3 are the values used as the detection limit of MG and BF, respectively. Stability constants are a very useful technique whose size is huge. Due to its usefulness, it has acquired an umbrella right in the fields of chemistry, biology, and medicine. No science subject is untouched by this. Stability constants of metal complexes are widely used in the various areas like pharmaceuticals as well as biological processes, separation techniques, analytical processes, etc. In the presented chapter, we have tried to explain this in detail by focusing our attention on the applications and solutions of stability of metal complexes in solution.
Stability or formation or binding constant is the type of equilibrium constant used for the formation of metal complexes in the solution. Acutely, stability constant is applicable to measure the strength of interactions between the ligands and metal ions that are involved in complex formation in the solution [11]. A generally these 1-4 equations are expressed as the following ways:
Thus
K1, K2, K3, … Kn are the equilibrium constants and these are also called stepwise stability constants. The formation of the metal-ligand-n complex may also be expressed as equilibrium constants by the following steps:
The parameters K and β are related together, and these are expressed in the following example:
Now the numerator and denominator are multiplied together with the use of [metal-ligand] [metal-ligand2], and after the rearranging we get the following equation:
Now we expressed it as the following:
From the above relation, it is clear that the overall stability constant βn is equal to the product of the successive (i.e., stepwise) stability constants, K1, K2, K3,…Kn. This in other words means that the value of stability constants for a given complex is actually made up of a number of stepwise stability constants. The term stability is used without qualification to mean that the complex exists under a suitable condition and that it is possible to store the complex for an appreciable amount of time. The term stability is commonly used because coordination compounds are stable in one reagent but dissociate or dissolve in the presence of another regent. It is also possible that the term stability can be referred as an action of heat or light or compound. The stability of complex [13] is expressed qualitatively in terms of thermodynamic stability and kinetic stability.
In a chemical reaction, chemical equilibrium is a state in which the concentration of reactants and products does not change over time. Often this condition occurs when the speed of forward reaction becomes the same as the speed of reverse reaction. It is worth noting that the velocities of the forward and backward reaction are not zero at this stage but are equal.
If hydrogen and iodine are kept together in molecular proportions in a closed process vessel at high temperature (500°C), the following action begins:
In this activity, hydrogen iodide is formed by combining hydrogen and iodine, and the amount of hydrogen iodide increases with time. In contrast to this action, if the pure hydrogen iodide gas is heated to 500°C in the reaction, the compound is dissolved by reverse action, which causes hydrogen iodide to dissolve into hydrogen and iodine, and the ratio of these products increases over time. This is expressed in the following reaction:
For the formation of metal chelates, the thermodynamic technique provides a very significant information. Thermodynamics is a very useful technique in distinguishing between enthalpic effects and entropic effects. The bond strengths are totally effected by enthalpic effect, and this does not make any difference in the whole solution in order/disorder. Based on thermodynamics the chelate effect below can be best explained. The change of standard Gibbs free energy for equilibrium constant is response:
Where:
R = gas constant
T = absolute temperature
At 25°C,
ΔG = (− 5.708 kJ mol−1) · log β.
The enthalpy term creates free energy, i.e.,
For metal complexes, thermodynamic stability and kinetic stability are two interpretations of the stability constant in the solution. If reaction moves from reactants to products, it refers to a change in its energy as shown in the above equation. But for the reactivity, kinetic stability is responsible for this system, and this refers to ligand species [14].
Stable and unstable are thermodynamic terms, while labile and inert are kinetic terms. As a rule of thumb, those complexes which react completely within about 1 minute at 25°C are considered labile, and those complexes which take longer time than this to react are considered inert. [Ni(CN)4]2− is thermodynamically stable but kinetically inert because it rapidly exchanges ligands.
The metal complexes [Co(NH3)6]3+ and such types of other complexes are kinetically inert, but these are thermodynamically unstable. We may expect the complex to decompose in the presence of acid immediately because the complex is thermodynamically unstable. The rate is of the order of 1025 for the decomposition in acidic solution. Hence, it is thermodynamically unstable. However, nothing happens to the complex when it is kept in acidic solution for several days. While considering the stability of a complex, always the condition must be specified. Under what condition, the complex which is stable or unstable must be specified such as acidic and also basic condition, temperature, reactant, etc.
A complex may be stable with respect to a particular condition but with respect to another. In brief, a stable complex need not be inert and similarly, and an unstable complex need not be labile. It is the measure of extent of formation or transformation of complex under a given set of conditions at equilibrium [15].
Thermodynamic stability has an important role in determining the bond strength between metal ligands. Some complexes are stable, but as soon as they are introduced into aqueous solution, it is seen that these complexes have an effect on stability and fall apart. For an example, we take the [Co (SCN)4]2+ complex. The ion bond of this complex is very weak and breaks down quickly to form other compounds. But when [Fe(CN)6]3− is dissolved in water, it does not test Fe3+ by any sensitive reagent, which shows that this complex is more stable in aqueous solution. So it is indicated that thermodynamic stability deals with metal-ligand bond energy, stability constant, and other thermodynamic parameters.
This example also suggests that thermodynamic stability refers to the stability and instability of complexes. The measurement of the extent to which one type of species is converted to another species can be determined by thermodynamic stability until equilibrium is achieved. For example, tetracyanonickelate is a thermodynamically stable and kinetic labile complex. But the example of hexa-amine cobalt(III) cation is just the opposite:
Thermodynamics is used to express the difference between stability and inertia. For the stable complex, large positive free energies have been obtained from ΔG0 reaction. The ΔH0, standard enthalpy change for this reaction, is related to the equilibrium constant, βn, by the well thermodynamic equation:
For similar complexes of various ions of the same charge of a particular transition series and particular ligand, ΔS0 values would not differ substantially, and hence a change in ΔH0 value would be related to change in βn values. So the order of values of ΔH0 is also the order of the βn value.
Kinetic stability is referred to the rate of reaction between the metal ions and ligand proceeds at equilibrium or used for the formation of metal complexes. To take a decision for kinetic stability of any complexes, time is a factor which plays an important role for this. It deals between the rate of reaction and what is the mechanism of this metal complex reaction.
As we discuss above in thermodynamic stability, kinetic stability is referred for the complexes at which complex is inert or labile. The term “inert” was used by Tube for the thermally stable complex and for reactive complexes the term ‘labile’ used [16]. The naturally occurring chlorophyll is the example of polydentate ligand. This complex is extremely inert due to exchange of Mg2+ ion in the aqueous media.
The nature of central atom of metal complexes, dimension, its degree of oxidation, electronic structure of these complexes, and so many other properties of complexes are affected by the stability constant. Some of the following factors described are as follows.
In the coordination chemistry, metal complexes are formed by the interaction between metal ions and ligands. For these type of compounds, metal ions are the coordination center, and the ligand or complexing agents are oriented surrounding it. These metal ions mostly are the transition elements. For the determination of stability constant, some important characteristics of these metal complexes may be as given below.
Ligands are oriented around the central metal ions in the metal complexes. The sizes of these metal ions determine the number of ligand species that will be attached or ordinated (dative covalent) in the bond formation. If the sizes of these metal ions are increased, the stability of coordination compound defiantly decreased. Zn(II) metal ions are the central atoms in their complexes, and due to their lower size (0.74A°) as compared to Cd(II) size (0.97A°), metal ions are formed more stable.
Hence, Al3+ ion has the greatest nuclear charge, but its size is the smallest, and the ion N3− has the smallest nuclear charge, and its size is the largest [17]. Inert atoms like neon do not participate in the formation of the covalent or ionic compound, and these atoms are not included in isoelectronic series; hence, it is not easy to measure the radius of this type of atoms.
The properties of stability depend on the size of the metal ion used in the complexes and the total charge thereon. If the size of these metal ions is small and the total charge is high, then their complexes will be more stable. That is, their ratio will depend on the charge/radius. This can be demonstrated through the following reaction:
An ionic charge is the electric charge of an ion which is formed by the gain (negative charge) or loss (positive charge) of one or more electrons from an atom or group of atoms. If we talk about the stability of the coordination compounds, we find that the total charge of their central metal ions affects their stability, so when we change their charge, their stability in a range of constant can be determined by propagating of error [18]. If the charge of the central metal ion is high and the size is small, the stability of the compound is high:
In general, the most stable coordination bonds can cause smaller and highly charged rations to form more stable coordination compounds.
When an electron pair attracts a central ion toward itself, a strong stability complex is formed, and this is due to electron donation from ligand → metal ion. This donation process is increasing the bond stability of metal complexes exerted the polarizing effect on certain metal ions. Li+, Na+, Mg2+, Ca2+, Al3+, etc. are such type of metal cation which is not able to attract so strongly from a highly electronegative containing stable complexes, and these atoms are O, N, F, Au, Hg, Ag, Pd, Pt, and Pb. Such type of ligands that contains P, S, As, Br and I atom are formed stable complex because these accepts electron from M → π-bonding. Hg2+, Pb2+, Cd2+, and Bi3+ metal ions are also electronegative ions which form insoluble salts of metal sulfide which are insoluble in aqueous medium.
Volatile ligands may be lost at higher temperature. This is exemplified by the loss of water by hydrates and ammonia:
The transformation of certain coordination compounds from one to another is shown as follows:
A ligand is an ion or small molecule that binds to a metal atom (in chemistry) or to a biomolecule (in biochemistry) to form a complex, such as the iron-cyanide coordination complex Prussian blue or the iron-containing blood-protein hemoglobin. The ligands are arranged in spectrochemical series which are based on the order of their field strength. It is not possible to form the entire series by studying complexes with a single metal ion; the series has been developed by overlapping different sequences obtained from spectroscopic studies [19]. The order of common ligands according to their increasing ligand field strength is
The above spectrochemical series help us to for determination of strength of ligands. The left last ligand is as weaker ligand. These weaker ligand cannot forcible binding the 3d electron and resultant outer octahedral complexes formed. It is as-
Increasing the oxidation number the value of Δ increased.
Δ increases from top to bottom.
However, when we consider the metal ion, the following two useful trends are observed:
Δ increases with increasing oxidation number.
Δ increases down a group. For the determination of stability constant, the nature of the ligand plays an important role.
The following factors described the nature of ligands.
The size and charge are two factors that affect the production of metal complexes. The less charges and small sizes of ligands are more favorable for less stable bond formation with metal and ligand. But if this condition just opposite the product of metal and ligand will be a more stable compound. So, less nuclear charge and more size= less stable complex whereas if more nuclear charge and small in size= less stable complex. We take fluoride as an example because due to their smaller size than other halide and their highest electro negativity than the other halides formed more stable complexes. So, fluoride ion complexes are more stable than the other halides:
As compared to S2− ion, O22− ions formed more stable complexes.
It is suggested by Calvin and Wilson that the metal complexes will be more stable if the basic character or strength of ligands is higher. It means that the donating power of ligands to central metal ions is high [20].
It means that the donating power of ligands to central metal ions is high. In the case of complex formation of aliphatic diamines and aromatic diamines, the stable complex is formed by aliphatic diamines, while an unstable coordination complex is formed with aromatic diamines. So, from the above discussion, we find that the stability will be grater if the e-donation power is greater.
Thus it is clear that greater basic power of electron-donating species will form always a stable complex. NH3, CN−, and F− behaved as ligands and formed stable complexes; on the other hand, these are more basic in nature.
We know that if the concentration of coordination group is higher, these coordination compounds will exist in the water as solution. It is noted that greater coordinating tendency show the water molecules than the coordinating group which is originally present. SCN− (thiocynate) ions are present in higher concentration; with the Co2+ metal ion, it formed a blue-colored complex which is stable in state, but on dilution of water medium, a pink color is generated in place of blue, or blue color complex is destroyed by [Co(H2O)6]2+, and now if we added further SCN−, the pink color will not appear:
Now it is clear that H2O and SCN− are in competition for the formation of Co(II) metal-containing complex compound. In the case of tetra-amine cupric sulfate metal complex, ammonia acts as a donor atom or ligand. If the concentration of NH3 is lower in the reaction, copper hydroxide is formed but at higher concentration formed tetra-amine cupric sulfate as in the following reaction:
For a metal ion, chelating ligand is enhanced and affinity it and this is known as chelate effect and compared it with non-chelating and monodentate ligand or the multidentate ligand is acts as chelating agent. Ethylenediamine is a simple chelating agent (Figure 1).
Structure of ethylenediamine.
Due to the bidentate nature of ethylenediamine, it forms two bonds with metal ion or central atom. Water forms a complex with Ni(II) metal ion, but due to its monodentate nature, it is not a chelating ligand (Figures 2 and 3).
Structure of chelating configuration of ethylenediamine ligand.
Structure of chelate with three ethylenediamine ligands.
The dentate cheater of ligand provides bonding strength to the metal ion or central atom, and as the number of dentate increased, the tightness also increased. This phenomenon is known as chelating effect, whereas the formation of metal complexes with these chelating ligands is called chelation:
or
Some factors are of much importance for chelation as follows.
The sizes of the chelating ring are increased as well as the stability of metal complex decreased. According to Schwarzenbach, connecting bridges form the chelating rings. The elongated ring predominates when long bridges connect to the ligand to form a long ring. It is usually observed that an increased a chelate ring size leads to a decrease in complex stability.
He interpreted this statement. The entropy of complex will be change if the size of chelating ring is increased, i.e., second donor atom is allowed by the chelating ring. As the size of chelating ring increased, the stability should be increased with entropy effect. Four-membered ring compounds are unstable, whereas five-membered are more stable. So the chelating ring increased its size and the stability of the formed metal complexes.
The number of chelating rings also decides the stability of complexes. Non-chelating metal compounds are less stable than chelating compounds. These numbers increase the thermodynamic volume, and this is also known as an entropy term. In recent years ligands capable of occupying as many as six coordination positions on a single metal ion have been described. The studies on the formation constants of coordination compounds with these ligands have been reported. The numbers of ligand or chelating agents are affecting the stability of metal complexes so as these numbers go up and down, the stability will also vary with it.
For the Ni(II) complexes with ethylenediamine as chelating agent, its log K1 value is 7.9 and if chelating agents are trine and penten, then the log K1 values are 7.9 and 19.3, respectively. If the metal ion change Zn is used in place of Ni (II), then the values of log K1 for ethylenediamine, trine, and penten are 6.0, 12.1, and 16.2, respectively. The log βMY values of metal ions are given in Table 1.
Metal ion | log βMY (25°C, I = 0.1 M) |
---|---|
Ca2+ | 11.2 |
Cu2+ | 19.8 |
Fe3+ | 24.9 |
Metal ion vs. log βMY values.
Ni(NH3)62+ is an octahedral metal complex, and at 25 °C its log β6 value is 8.3, but Ni(ethylenediamine)32+ complex is also octahedral in geometry, with 18.4 as the value of log β6. The calculated stability value of Ni(ethylenediamine)32+ 1010 times is more stable because three rings are formed as chelating rings by ethylenediamine as compared to no such ring is formed. Ethylenediaminetetraacetate (EDTA) is a hexadentate ligand that usually formed stable metal complexes due to its chelating power.
A special effect in molecules is when the atoms occupy space. This is called steric effect. Energy is needed to bring these atoms closer to each other. These electrons run away from near atoms. There can be many ways of generating it. We know the repulsion between valence electrons as the steric effect which increases the energy of the current system [21]. Favorable or unfavorable any response is created.
For example, if the static effect is greater than that of a product in a metal complex formation process, then the static increase would favor this reaction. But if the case is opposite, the skepticism will be toward retardation.
This effect will mainly depend on the conformational states, and the minimum steric interaction theory can also be considered. The effect of secondary steric is seen on receptor binding produced by an alternative such as:
Reduced access to a critical group.
Stick barrier.
Electronic resonance substitution bond by repulsion.
Population of a conformer changes due to active shielding effect.
The macrocyclic effect is exactly like the image of the chelate effect. It means the principle of both is the same. But the macrocyclic effect suggests cyclic deformation of the ligand. Macrocyclic ligands are more tainted than chelating agents. Rather, their compounds are more stable due to their cyclically constrained constriction. It requires some entropy in the body to react with the metal ion. For example, for a tetradentate cyclic ligand, we can use heme-B which forms a metal complex using Fe+2 ions in biological systems (Figure 4).
Structure of hemoglobin is the biological complex compound which contains Fe(II) metal ion.
The n-dentate chelating agents play an important role for the formation of more stable metal complexes as compared to n-unidentate ligands. But the n-dentate macrocyclic ligand gives more stable environment in the metal complexes as compared to open-chain ligands. This change is very favorable for entropy (ΔS) and enthalpy (ΔH) change.
There are so many parameters to determination of formation constants or stability constant in solution for all types of chelating agents. These numerous parameters or techniques are refractive index, conductance, temperature, distribution coefficients, refractive index, nuclear magnetic resonance volume changes, and optical activity.
Solubility products are helpful and used for the insoluble salt that metal ions formed and complexes which are also formed by metal ions and are more soluble. The formation constant is observed in presence of donor atoms by measuring increased solubility.
To determine the solubility constant, it involves the distribution of the ligands or any complex species; metal ions are present in two immiscible solvents like water and carbon tetrachloride, benzene, etc.
In this method metal ions or ligands are present in solution and on exchanger. A solid polymers containing with positive and negative ions are ion exchange resins. These are insoluble in nature. This technique is helpful to determine the metal ions in resin phase, liquid phase, or even in radioactive metal. This method is also helpful to determine the polarizing effect of metal ions on the stability of ligands like Cu(II) and Zn(II) with amino acid complex formation.
At the equilibrium free metal and ions are present in the solution, and using the different electrometric techniques as described determines its stability constant.
This method is based upon the titration method or follows its principle. A stranded acid-base solution used as titrate and which is titrated, it may be strong base or strong acid follows as potentiometrically. The concentration of solution using 103− M does not decomposed during the reaction process, and this method is useful for protonated and nonprotonated ligands.
This is the graphic method used to determine the stability constant in producing metal complex formation by plotting a polarograph between the absences of substances and the presence of substances. During the complex formation, the presence of metal ions produced a shift in the half-wave potential in the solution.
If a complex is relatively slow to form and also decomposes at measurable rate, it is possible, in favorable situations, to determine the equilibrium constant.
This involves the study of the equilibrium constant of slow complex formation reactions. The use of tracer technique is extremely useful for determining the concentrations of dissociation products of the coordination compound.
This method is based on the study of the effect of an equilibrium concentration of some ions on the function at a definite organ of a living organism. The equilibrium concentration of the ion studied may be determined by the action of this organ in systems with complex formation.
The solution of 25 ml is adopted by preparing at the 1.0 × 10−5 M ligand or 1.0 × 10−5 M concentration and 1.0 × 10−5 M for the metal ion:
The solutions containing the metal ions were considered both at a pH sufficiently high to give almost complete complexation and at a pH value selected in order to obtain an equilibrium system of ligand and complexes.
In order to avoid modification of the spectral behavior of the ligand due to pH variations, it has been verified that the range of pH considered in all cases does not affect absorbance values. Use the collected pH values adopted for the determinations as well as selected wavelengths. The ionic strengths calculated from the composition of solutions allowed activity coefficient corrections. Absorbance values were determined at wavelengths in the range 430–700 nm, every 2 nm.
For a successive metal complex formation, use this method. If ligand is protonate and the produced complex has maximum number of donate atoms of ligands, a selective light is absorbed by this complex, while for determination of stability constant, it is just known about the composition of formed species.
Bjerrum (1941) used the method stepwise addition of the ligands to coordination sphere for the formation of complex. So, complex metal–ligand-n forms as the following steps [22]. The equilibrium constants, K1, K2, K3, … Kn are called stepwise stability constants. The formation of the complex metal-ligandn may also be expressed by the following steps and equilibrium constants.
Where:
M = central metal cation
L = monodentate ligand
N = maximum coordination number for the metal ion M for the ligand
If a complex ion is slow to reach equilibrium, it is often possible to apply the method of isotopic dilution to determine the equilibrium concentration of one or more of the species. Most often radioactive isotopes are used.
This method was extensively used by Werner and others to study metal complexes. In the case of a series of complexes of Co(III) and Pt(IV), Werner assigned the correct formulae on the basis of their molar conductance values measured in freshly prepared dilute solutions. In some cases, the conductance of the solution increased with time due to a chemical change, e.g.,
It is concluded that the information presented is very important to determine the stability constant of the ligand metal complexes. Some methods like spectrophotometric method, Bjerrum’s method, distribution method, ion exchange method, electrometric techniques, and potentiometric method have a huge contribution in quantitative analysis by easily finding the stability constants of metal complexes in aqueous solutions.
All the authors thank the Library of University of Delhi for reference books, journals, etc. which helped us a lot in reviewing the chapter.
As a company committed to the wider dissemination of knowledge, IntechOpen supports the OAI Metadata Harvesting Protocol (OAI-PMH Version 2.0).
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\\n\\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
\\n\\nAs a Data Provider, metadata for published Chapters and Journal Articles are available via our interface at the base URL:http://www.intechopen.com/oai/?.
\\n\\nREQUESTS
\\n\\nYou can find out more about the Protocol by visiting the Open Archives website. For additional questions please contact us at info@intechopen.com.
\\n\\nDATABASES
\\n\\nDatabases, repositories and search engines that provide services based on metadata harvested using the OAI metadata harvesting protocol include:
\\n\\nBASE - Bielefeld Academic Search Engine
\\n\\nOne of the world's most powerful search engines, used primarily for academic Open Access web resources.
\\n\\n\\n\\nA search engine for online catalogues of publications from all over the world.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'The OAI-PMH (Open Archives Initiative Protocol for Metadata Harvesting) is used to govern the collection of metadata descriptions and enables other archives to access our database. The Protocol has been developed by the Open Archives Initiative, based on ensuring interoperability standards in order to ease and promote broader and more efficient dissemination of information within the scientific community.
\n\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
\n\nAs a Data Provider, metadata for published Chapters and Journal Articles are available via our interface at the base URL:http://www.intechopen.com/oai/?.
\n\nREQUESTS
\n\nYou can find out more about the Protocol by visiting the Open Archives website. For additional questions please contact us at info@intechopen.com.
\n\nDATABASES
\n\nDatabases, repositories and search engines that provide services based on metadata harvested using the OAI metadata harvesting protocol include:
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\n\nOne of the world's most powerful search engines, used primarily for academic Open Access web resources.
\n\n\n\nA search engine for online catalogues of publications from all over the world.
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