Calcined clays are the only potential materials available in large quantities to meet the requirements of eco-efficient cement-based materials by reducing the clinker content in blended cements or reducing the cement content in concrete. More than 200 recent research papers on the idea of replacing Portland cement with large amounts of calcined clay are presented and discussed in detail. First, the fundamental information about the properties and structure of clay minerals is described. Then, the process of activation and hydration of clays is discussed, including the methods of pozzolanic activity assessment. Additionally, various testing methods of clays from different worldwide deposits are presented. The application of calcined clay in cement and concrete technology is then introduced. A separate chapter is devoted to lime calcined clay cement. Then an influence of calcined clay on durability of concrete is summarized. Finally, conclusions are formulated. Sustainable development, understood as progress that meet the needs of the present without compromising the ability of future generations to meet their needs, is now the basic idea behind the current paradigm of technological progress. The greatest threat to the achievement of the objectives of sustainable development is the excessive emission of greenhouse gases, including, above all, carbon dioxide, which results in global warming with many serious negative consequences for future development and its prospects.The building industry makes a significant contribution to increasing the carbon dioxide content in the atmosphere, with cement production accounting for 5% of global carbon dioxide emissions  being it2 emissions to the atmosphere by the cement and concrete industry are the production of blended cements that reduce the amount of clinker and the use of supplementary cementitious materials (SCM), mainly pozzolans, in the concrete technology. A pozzolan, according to ASTM C125, is “a siliceous and aluminous material which, in itself, possesses little or no cementitious value but which will, in finely divided form in the presence of moisture, react chemically with calcium hydroxide at ordinary temperature to form compounds possessing cementitious properties” [The possibilities of reducing the energy intensity of cement production are limited, although it is already possible to reduce heat consumption to 2.9 GJ/t of clinker. The use of alternative fuels further reduces carbon dioxide emissions from fossil fuels. However, the use of limestone in clinker production cannot be eliminated or reduced. Therefore, solutions to further reduce COThe most commonly used SCM so far is fly ash from coal power plants. However, this additive, which is used in the production of both cement and concrete, is slowly losing its primary importance due to the progressive decommissioning of coal and lignite power plants. As a result, the supply of fly ash will be significantly reduced in the near future. Another cement additive used to reduce clinker content is a granulated blast furnace slag. However, it has no potential to replace fly ash, not least because its global supply is far below potential demand. Additionally, it is only available in countries where the steel industry exists. However, even where it is available, its share in blended cements production is not large. In India, for example, Portland slag cement accounts for only about 8% of total cement production, while ordinary Portland cement accounts for 24% of production, and Portland pozzolana cement accounts for 65%, where the main addition is fly ash ,4.The decreasing supply of fly ash from the power industry is encouraging the search for new sources of pozzolan additives for cement and concrete production. One of the directions of this search is ashes obtained from biomass combustion, . AnotherMetakaolin was shown to be the best clay raw material for SCMs production, but in its pure form it is only found in a limited number of deposits, so its availability is not sufficient to meet the needs of the building materials industry. It is also in the focus of interest of other industries ,7. For tClay is a widely spread material in the world, cheap and easily accessible . At the In general, the literature on the activation of clay minerals and their use in civil engineering is very rich and covers a wide range of issues. It would be very difficult to discuss this vast area of research in one review article, so certain assumptions on the scope of this review were made First of all, it focuses on calcined clays used as SCM in binders, where cement is the dominant component, and in the cement-based concrete. Outside the scope of interest remain cement-free binders based on calcined clays, which are the basis of geopolymers, as well as other alkaline-activated binders . Issues that do not fall within the assumed topics of the article are mentioned where it was indicated for various reasons.3), a separate section is also devoted to it. The next chapter discusses the results of research on the impact of calcined clays on concrete durability. Numerous publications on calcined clay, which cannot be clearly classified as one of the above thematic areas, have been placed in a separate section devoted to suitable aspects of the application of these materials. The summary presents the conclusion of the literature reviewThe paper is divided into eight thematic sections. The first section describes a fundamental knowledge about clay minerals and publications on clays from various deposits in the world. In the next section the topic of clay minerals activation with emphasis on calcination process and research of hydration mechanisms and pozzolanic activity with factors influencing them are presented. A separate section is devoted to the role of calcined clays in concrete technology (as SCM) and in blended cements production. Due to the wealth of literature devoted to lime calcined clay cement  and octahedral (O) layers . The T lions see . − groups and other anions , which are located in the corners of octahedrons, but are not shared with the T layer [At the contact of T and O layers there is a layer of oxygen atoms . Additionally, the O layer contains oxygen atoms  forming OH T layer . The division of minerals into 1:1 (TO) or 2:1 (TOT) groups results from the repetitive arrangement of layers of the one or the other type see . This diMinerals 1:1 include two groups: the kaolin group and the serpentine group. The first group includes: kaolinite, dickite, nicrite, halloysite, hisingerite. To the second group belong, among others, lizardite, antigorite, chrysotile, caryopilite, pyrosmalite, polygonal serpentines and polyhedral serpentines. Minerals 2:1 form a large group of which the following should be mentioned: pyrophyllite and talc both of ideally layered structure; mica, more than 200 variants , of whicA more detailed discussion of the properties and structure of clay minerals is beyond the scope of this review. In the following section, the minerals which are part of calcined clays and which determine their properties are discussed in more detail. The discussion is focused on their properties, which are important in the activation process and determine their properties as pozzolan materials. The article describes also factors influencing the optimization of activation process. The most important clay minerals, which are subject to temperature activation and, therefore, are discussed in more detail in this paper, are kaolinite and montmorillonite, which also occurs in the form of variants called Ca-montmorillonite and Na-montmorillonite ,18,19. AKaolinite and the product of its calcination, i.e., metakaolinite, are the most thoroughly tested of the clay minerals that are part of the clays subjected to calcination in order to use them as SCMs due to their pozzolanic activity. Part of this literature can be found in ,21. OtheIt is not only montmorillonite that exhibits pozzolanic activity in its raw state. Among such minerals we can also include illite, kaolinite and muscovite ,25,26. HTo the group of kaolinites, i.e., minerals 1:1 belongs halloysite—a lesser known close “cousin” of kaolinite. Both these minerals have identical chemical structure with the only one difference that halloysite may contain two additional water molecules in the interlayer space. Halloysite is, therefore, sometimes referred to as hydrated kaolinite. This small difference has significant consequences for the structure of this mineral, which forms different forms such as tubes, spheres and laths ,29. WateMuscovite is also included among the clay minerals that show pozzolanic activity after appropriate heat treatment, although in this case the results are ambiguous. Ambroise , by examAnother clay mineral which has been studied due to its potentially pozzolanic properties is sepiolite ,32. It iIllit is one of the minerals which show practically no pozzolanic properties in their raw state. Heat treatment carried out at high temperatures (930–950 °C) both pure mineral with small admixtures  as well Mixed-layer minerals, which are characterised by the presence of different types of layers, are very common in clays. According to Weaver , it is e4+ ions, which may partially explain the discrepancy in the value of the optimal calcination temperature in relation to the findings of He et al.The study of natural mixed-layer mineral of similar composition (illite/smectite in the ratio 70/30) was conducted by Garg and Skibsted . In thisLemma et al.  study ofRaw clays usually have a moderate or low pozzolanic activity. To increase it, they need to be activated. As a result of activation, clay minerals undergo processes of dehydroxylation and amorphisation and the accompanying change in coordination of Al ions. Those processes lead to, among other things, greater solubility of Al and Si ions and their greater reactivity, which is a basic condition for the demonstration of pozzolanic activity by clay minerals . The actThe effectiveness of the thermal activation process, and consequently pozzolanic activity of the obtained material, depends on many factors. These include: calcination temperature, particle size and shape, time and others . The mos− groups [The process of dehydroxylation, i.e., tearing off OH− groups , leads t− groups . This ef− groups ,47. At t− groups ,49. Mont− groups . Neißer-− groups  have stuAnother variable of importance in the thermal activation process is time. Its impact has been studied by Chakchouk et al. . They deThe duration of the thermal activation process is usually counted in hours or minutes when using fluidized bed reactors . This ty4 °C/s [However, regardless of whether the process of soak-calcination takes several minutes or several hours, the activation process known as flash-calcination, which lasts from fractions of a second to several seconds, can be clearly distinguished from it ,53,54,554 °C/s ,54. Such4 °C/s ,53,54. M0 coefficient (it is defined further in the article). They showed, that in case of kaolinite with disordered structure (P0 = 0.68), that it was enough to heat the material at 650 °C for 45 min for full dehydroxylation whereas, in the case of kaolinite with well-ordered structure (P0 = 1.4), such time allowed dehydroxylation of 71–95% of kaolinite. The relationship between kaolinite dehydroxylation degree and lime consumption from CaO saturated solution after 28 days was also shown. Although the level of linear regression adjustment (R2 = 0.73) indicates that the kaolinite dehydroxylation level is an important but not the only factor shaping the calcined clay pozzolan activity even if it contains more than 75% of kaolinite.It is not only time, temperature or particle size that determine the success of the calcination process. Bich et al.  studied The calcination process, due to its complexity resulting from a number of parameters regulating it, as well as from various possible variants of its execution, has also gained mathematical models describing it. Teklay et al. ,57 develAmong publications devoted to the activation of clays and clay minerals, there are also those concerning the conduct of this process with the use of additional substrates aimed at changing certain characteristics of the finished material. The primary purpose of such additives or admixtures is to increase pozzolanic activity . As an eThe increase in kaolinite pozzolanic activity was also obtained by Ghorbel and Samet , who addIt is assumed that the largest pozzolanic activity characterizes kaolinite, which also has the lowest activation temperature range. According to He et al. , calcina− groups were removed. As a result of the simulation, a disordered mineral structure was obtained, in which the silicon layers showed little disorder, while the aluminium layers were significantly disordered and about 20% of the Al ions gained 5-fold coordination. It is less stable than the original six-fold coordination and four-fold coordination, which was adopted by most Al ions after calcination. This results in greater solubility and, as a consequence, also pozzolanic activity. Interestingly, the Al ions only moved within their own layer, as they were held back from further migration by a less affected silicon layer. Metakaolinite, which is a product of kaolinite calcination, is a transition phase during the thermal transformation of kaolinite into mullite, which is an inactive pozzolanic mineral. Sperinck et al.  presentscis-vacant (cv) and trans-vacant (tv) modified layers in determining this temperature. Both these variants of layers differ in the distance between the nearest hydroxyl groups. In tv 2:1 layers the bond length is 2.45 Å ± 0.05 Å, whereas in cv 2:1 layers it is considerably longer and is 2.85–2.88 Å. Hydrogen, which in the process of dehydroxylation passes from one group OH− to another creating a water molecule, needs a little more energy in the latter case. This explains well the difference in temperature required for full hydroxylation between the 2:1 group minerals.Minerals of the 2:1 group are characterised by a fairly wide range of temperatures at which dehydroxylation occurs. As far as illite is concerned, the temperature required for this process is 650 °C, but further heating is possible (up to 930 °C), which leads to an increase in its pozzolanic activity, probably due to the progressive amorphisation of the structure. According to He et al. , Ca-montStudies on the process of montmorillonite calcination, using the NMR technique, were conducted by Garg and Skibsted . They shThe less frequently occurring clay minerals, and thus slightly less popular among researchers, include pyrophylite, whose dehydroxylation processes and effects of thermal treatment are presented in papers ,66. AddiAmong the publications devoted to the study of clay activation, paper  should bSince deposits of pure clays containing only one type of clay mineral are not rich enough to meet the growing demand of the construction industry for calcined clays as supplementary cementitious materials, it is important to assess the clays from existing deposits in terms of the possibility of using their resources as raw materials for the production of SCMs. The pozzolanic activity of clay is not a simple sum of the activity of its individual constituent minerals. The co-occurrence of some of them may give a synergy effect, but in other configurations the potential of any of the components may not be fully exploited. Hence the need to develop a methodology for the assessment of specific deposits arises in terms of their suitability for activation.2O3 content, which should be more than 18%, then the ratio of Al2O3 to SiO2 content, which should be higher than 0.3 and, finally, the loss on ignition, which should not be less than 7%. Due to the deleterious effects of calcite and pyrite, the authors have added two additional conditions: CaO < 3% and SO3 < 3%. The authors are of the opinion that first of all, the exploitation should be carried out with the use of aluminium deposits containing over 40% of kaolinite. However, in order to take into account the pozzolanic activity of 2:1 group clays, they proposed a parameter defined as kaolinite equivalent calculated according to Equation (1):m(x) is the mass of the mineral after heat treatment at a given temperature x. Diaz et al.  presenteA promising tool for a preliminary assessment of potential clay minerals’ pozzolanic activity may be cation exchange capacity, but not yet at this stage, as the author himself admits in his paper . The dev2O3-2SiO2 and Ca(OH)2, which in the case of concrete comes from the hydration of cement. The presence of water is also necessary for this reaction, as the reaction products are hydrates. As a result of the pozzolan reaction, CSH gel (CaO·SiO2·H2O) and hydrated calcium aluminates  are produced, as well as hydrated calcium aluminosilicates of the hydrogehlenite type C2ASH and hydrogarnets (C3AS3-C3AH6). Carboaluminates 2·10.5H2O) may also be formed in the presence of carbon dioxide or limestone filler [The pozzolan reaction occurs between Ale filler ,75,76,772 content and products of its reaction and changes in the content of these compounds over time. These are methods using XRD, TGA and DTA techniques, as well as methods based on solution titration, i.e., the Fratini test and its simplification, also referred to as the saturated lime (SL) [2 in which the tested material is placed [There are many different methods of determining pozzolanic activity. They are described among others in ,58,78,79ime (SL) . Among ts placed ,81,82,83s placed ,85. A wide review of methods of testing the pozzolanic activity is presented in paper of Tkaczewska . The met2 mass and the remaining unbound mass. The latter is determined in a thermal test from the loss in mass of the sample in the temperature range 490–510 °C, which corresponds to the decomposition of portlandite. This method has several weaknesses which must be taken into account when using it. First of all, the temperature of calcium hydroxide decomposition may vary depending on the alkali content or even grain size [One of the methods is the measurement of portlandite consumption by SCM using thermal analysis methods, i.e., TGA in combination with DTA . In thisain size . Anotherain size  and they2 = 0.971), while the mass loss in the moisture analyser is slightly higher. With appropriate assumptions, it is possible to test the pozzolanic activity of the materials by determining the amount of water lost by the hydration products, which increases with the progress of the pozzolanic reaction. TGA/DTA testing requires expensive equipment, so it is not a method that can be used in many laboratories that are less well equipped. To address such situations, Mendoza and Tobón  have car2 suspension at 40 °C for eight days [− ions  and Ca2+ ions determined in the test is compared with the calcium hydroxide solubility isotherm curve. The location of the result below the curve means that the material is active pozzolan, the greater its activity, the greater the distance of the result beneath the curve.Fratini is identified with at least two different methods to test the activity of pozzolan. The first one ,91,92 coght days . During The second Fratini method is the strength method. It consists in testing the strength of two series of mortar samples prepared with the use of cement and the tested material in the amount of 30–50% of the hot water. One series of samples is stored for seven days in water at a temperature of 20 °C, and the other only three days, after which it is transferred to water at 50 °C for another four days. The difference in strength of both series of samples proves pozzolanic activity of the tested material . The method according to the PN-EN 450-1:2012 standard  is basedApart from testing the strength of mortars containing cement, there are also methods based on testing the strength of mortars prepared from slaked lime and the tested material. One such method is contained in the Serbian standard SRPS B.C1.018:2015 . A mixtuThe method based on the study of the influence of pozzolanic material on the strength of cement mortar is also Graff’s method . In thisThe method contained in the withdrawn Russian standard GOST 6269-54  is simil2 and Al2O3 in it. The test material should be placed for 1.5 h in a 1-molar solution of sodium hydroxide at 80 °C. The total content of dissolved SiO2 and Al2O3 above 20% indicates that the material shows pozzolanic activity. The same standard also includes a method based on testing the strength of the lime - pozzolanic mortar. Samples of such mortar should be stored for seven days at 65 °C in a humid atmosphere, then cooled to 23 °C and kept at this temperature for another 21 days, also in a humid atmosphere. The material exhibits adequate pozzolanic activity if the samples reach compressive strength ≥4.1 MPa. ASTM C379-65T was withdrawn in 1966 and replaced by ASTM C593-95 [Chemical methods include the method contained in the withdrawn ASTM C379-65T . It assu C593-95 , which o2 solution for 16 h and then determining the calcium hydroxide content in the filtrate [2 content in the initial solution and in the filtrate. Nino et al. [2 in the solution. After heating the solution to 100 °C, part of the calcium hydroxide was precipitated, but during the test, as part of Ca(OH)2 reacted with kaolin, the precipitate dissolved, keeping the solution saturated. The test was extended to 24 h and the solution was mixed at 150 rpm.Chapelle test consists in boiling the pozzolana sample in Ca(OH)filtrate . A measuo et al.  have mod2, Al2O3 and Fe2O3 that have entered the solution are determined. Then a further aliquot of the test material is mixed 1:1 with Ca(OH)2 adding enough water to give the prepared mixture a plastic consistency. The prepared mixture is stored for three days in a humid atmosphere and then it is placed in water at 15 °C. After one, four and 26 weeks from the preparation of the mixture, part of the mixture is taken, dried, ground and the SiO2, Al2O3 and Fe2O3 content is determined in the same way as in the case of the test sample itself (shaking in 30% HCl). Pozzolan activity is measured by the increase in the amount of leached oxides in a sample of test material with Ca(OH)2 compared to a reference sample containing the test material itself. Another chemical method is the Feret–Florentin method, about which Feret mentioned in  and whicFeret himself is the author of the method in which pozzolanic activity is tested firstly by treating the material with a 30% solution of HCl and then with a 25% solution of NaOH. The measure of pozzolanicity is the amount of material tested, expressed as a percentage, which has migrated to the solution. In order to consider that the material has a high pozzolanic activity, at least 60% of its mass should be dissolved. The simplification of the Feret method is the Jarrige and Decreux method . It cons2 is present in the test material, it reacts with calcium oxide or alite to form HCl-soluble calcium silicates. Cement with added quartz sand does not change significantly its solubility in HCl.The Guillaume method  consists2 content. The tests are carried out after different hardening periods. A sample of the paste should be ground and then the 30–60 μm fraction should be separated. The specific surface area is determined by the BET method and the free Ca(OH)2 content by the ethylacetylacetate method (Franke method) [The method proposed by Battaglino and Schipp  is based method) . A mater3 method . A detailed description of it and the underlying research can be found in [3) and potassium hydroxide as well as potassium sulphate both added in such quantities that the reaction environment has a similar composition to a pore liquid in concrete. Detailed compositions of the mixtures are given in the above mentioned publications. At the method development stage the prepared mixture was tested in a calorimeter at 20 °C and 40 °C for seven days. Since the amount of heat released at the higher of these temperatures after 1 day is equal to the amount released at the lower one after six days, further analyses were based on the results obtained after one day at 40 °C. The second variant of this method starts with the preparation of a mixture with the same composition as the first variant. This mixture is placed in a sealed container and treated at 40 °C for one day. The sample is then dried at 110 °C until its mass change per day becomes less than 0.5%. The sample so dried is exposed to a temperature of 400 °C for two hours and then cooled to 110 °C. The sample is weighed before and after heating at 400 °C and the quantity of water bound in the hydration products is determined from Equation (3):Another suggestion for the test of pozzolanic activity is the Rfound in ,114. Thib is the quantity of water bound by the hydration products, ms is the mass of the sample after drying to a constant mass but before exposure to 400 °C and mc is the mass of the sample after heating and then cooling to 110 °C. According to [2 kept at a constant temperature of 40 ± 1 °C, in which a sample of the tested material, dried earlier at 105 ± 5 °C, is placed. Pozzolan activity is measured by the difference of the compensated conductivity of the solution at the start of the test and after 120 s. According to the classification proposal of [In Equation (3) Wrding to , the resrding to , developrding to . The ideposal of , a materposal of  proposedEach method has its strengths and weaknesses, so it is best to use more than one method to obtain as complete a picture as possible of pozzolanic activity of the tested material. Danatello et al.  comparin3 calorimetry according to [3 calorimetric test can also be useful in the evaluation of this type of clays.Maier et al.  examinedrding to  . An XRD study after calcination showed that the time and temperature were sufficient to transform the kaolinite into metakaolinite. After calcination, pozzolanic activity was also determined by the Fratini test and the electrical conductivity test (previously described). The compressive strength of mortars in which 30% of cement was replaced with ground calcined clay was also tested. On the basis of the results of the latter test, a model was proposed in which the strength of the mortars , in which 30% OPC was replaced with ground calcined clay, depends on the content of kaolinite in the clay, on the specific surface defined by the Blaine method and on the inverse of the P0 coefficient. The authors proved that the results obtained from the application of the proposed model are highly consistent with the test results. Thus, they showed that the calcined clays’ pozzolanic activity depends not only on kaolinite content but also on the degree of order of its structure and specific surface of the clays after calcination and grinding.Tironi et al. ,118 haverding to , kaolin Huenger et al.  selectedBeuntner and Thienel ,121 presPapers ,123,124 Akasha  presenteChakchouk et al.  have selThe reported results of the research indicate that it is necessary and advisable to develop a research protocol which could be used as a standard for examining clays from unexplored local deposits. The diversity of clays from different deposits in the same country indicates the need to take into account the specific mineral composition of a particular clay in developing and optimising its calcination technology.The issue of calcined clays as SCM cannot be considered in isolation from the technological determinants related to the use of this active pozzolanic material in the production of blended cements and concrete. In  Samet et®. Four types of Portland clinker and three types of clays  were used in the research. The clay was added to the clinker in amounts of 20% and 40%. Additionally, the anhydrite was added in a different amount (2% or 4%). The research included compressive strength after two, seven and 28 days and studies of hydration products after 3 h and two days. The authors came to the conclusion that there is space to improve the strength parameters of calcined clay cements by selecting both the appropriate chemical and mineralogical composition of the raw materials and adjusting the amount of sulphates accordingly.The issue of optimization of the composition of cement blends with calcined clays was also considered by Pierkes et al. . Due to Siddique and Klaus  have revPaiva et al.  have stuResearch on the compatibility of superplasticisers with cement mixes containing metakaolin and limestone was undertaken by Zaribaf et al. . They usAn extended analysis of the efficiency of superplasticizers depending on the mineralogical composition of calcined clay and the type of cement (OPC or PLC) was conducted by Sposito et al. . Apart fNied et al.  investigBeuntner et al.  presenteThe use of calcined clays as binder components can be combined with the simultaneous use of other types of pozzolan. Mechti et al.  presenteTwo different pozzolana  in cement mixes were also used by Ng and Østnor . This coWorkability and hydration of blended cements with calcined illitic clay have been studied by Marchetti et al. . They usMachner et al.  have stuAs it can be seen that the addition of calcined clay reduces the early strength of cement composites due to lower reactivity of pozzolana. Paper  presentsThere is a consensus among researchers that the replacement of part of cement with metakaolin (up to 15%) reduces drying shrinkage of concrete compared to material without metakaolin or with silica fume ,145,146.A review of the studies on the use of calcined clays in cement and concrete technology shows an overwhelming predominance of articles devoted to various aspects of application of metakaolin. It is the best-researched calcined clay mineral, although even in its case the results obtained are far from being generalised. Although kaolin is a grateful object both for testing and for subsequent use after calcination, due to its limited availability, more extensive research into the properties and application of clays with different mineralogical compositions is necessary. In addition, many of the work presented is based on results obtained using pastes or mortars cement. Concrete testing results are in a clear minority. This is probably due to the need to produce larger amounts of calcined clay with homogeneous parameters, which can be difficult in laboratory conditions. Nevertheless, this is an important direction of research that deserves more attention.3 [2 emissions to the atmosphere, and which at the same time is not inferior to ordinary Portland cement with a clinker content of at least 90%. The abundance of raw clays and limestone is also an important factor in the development of LC3 production, in contrast to the shrinking resources of good quality fly ash or even their unavailability in some countries.The cement consisting of Portland clinker, calcined clay (preferably rich in kaolinite), calcium carbonate and gypsum is described in literature as LC3 . It is a3 is 50% of ground Portland clinker, 30% of ground calcined clay, 15% of ground limestone and 5% of ground gypsum. Such a mixture is sometimes referred to in the literature as LC3-50. Other proportions of components are also possible [The most common composition for the LCpossible , but it possible ,150, rea3 production is its cost and profitability. Papers [3 is economically viable if the following conditions are met: the cost of fly ash will be high, the quality of fly ash will be low, the acquisition of fly ash will require longer transport than the acquisition of clay and the quality of the extracted clay will reduce the amount of clinker in cement. Most of these conditions are already met, for example, in countries which do not have sources of good quality fly ash. Given the restrictions on the use of fossil fuels in energy production, these conditions may soon be met automatically. An important aspect of LC. Papers ,152 pres3 is no less important. Several publications have been devoted to this issue. In papers [3. The results of the study showed a much finer pore structure in concrete with LC3, which was proved in the mercury intrusion porosimetry study. Additionally, the conductivity of the concrete obtained in this way turned out to be lower, which allows one to assume that it will have higher resistance to the penetration of harmful ions into its structure. In short, its durability can be predicted to be significantly higher than that of other concrete series compared in the work.Apart from the economic aspect, the durability and performance of concrete with LCn papers ,154 the 3. The study covered investigation of concrete with cement, in which 15%, 30% and 45% of the mass was replaced by a mixture of calcined clay (containing about 50% metakaolin and 50% quartz) and limestone in a ratio of 2:1. For comparison, two series of concrete with OPC were used. One of them had the same aggregate, water and binder ratio as the LC3 concrete series, and the other modified proportions and quantities. The results indicate that concrete with LC3 and 15% cement exchange rate showed higher carbonation resistance than concrete with OPC. At 30% a slight advantage was gained by concrete with OPC, and at a 45% cement exchange rate to a mixture of calcined clay and limestone, concrete with LC3 showed a high carbonation rate. The same authors [3 was characterized by worse workability. As far as strength was concerned, the highest was reached by concrete with a 15% exchange rate of cement, which also had the lowest porosity. As far as drying shrinkage is concerned, all series of LC3 concrete were lower than OPC concrete. Khan et al.  discusse authors  presente3  with respect to carbonation. This protocol included the determination of indicators of the carbonation process, such as diffusivity of CO2, hydration and carbonation products, total possible carbonation, and pH change due to the carbonation and rate of carbonation. The paper also contains a suggestion to determine the above mentioned elements and the possibility to apply the presented approach to other issues concerning concrete durability.An interesting approach to the issue of carbonation is presented in paper of Joseph et al. . The aut3 to chloride diffusion. Three series of concrete were made for research purposes. One contained only general purpose cement corresponding to Type I cement according to ASTM C150/C150M [3 in concrete significantly increased its resistance to chloride diffusion. The continuation of the research on chloride diffusion resistance Nguyen et al. presented in [3. The difference between the results of concrete made with different types of calcined clay turned out to be insignificant, which led the authors to conclude that it is crucial in this case to properly select the proportion of cement exchanged for calcined clay to meet the requirements of specific strength of concrete exposed to chloride ingressives. Nguyen and Castel  evaluate50/C150M . In the ented in , where tented in ) to calc3 concrete and concrete with fly ash compared to it. The authors conducted extensive simulations taking into account many elements affecting the course of chloride diffusion in hardened concrete. The results showed that both concretes had comparable service life even though the LC3 concrete contained less clinker. The conclusions also indicated important parameters that should be introduced to the simulation in order for the results to be reliable.A different approach to chloride diffusion research was applied by Yang et al. ; they di3. This issue is important because of the lower alkalinity of this type of concrete due to the lower amount of portlandite, which is consumed by calcined clay in the pozzolanic reaction. The research, carried out over 500 days, allowed the conclusion to be drawn that performance of reinforced concrete prepared with LC3 was comparable to that for concrete with OPC in the propagation phase. Nguyen and Castel  presente3. They presented the results of corrosion testing of steel in three concrete mixes prepared with the use of: OPC, a blend of 70% OPC with 30% of fly ash and a blend of 50% OPC with a 50% mixture of limestone and calcined clay. In their previous work [3 showed very high resistivity, which is a good predictor of resistance to chloride ion penetration and, consequently, to corrosion of reinforcing steel. As a continuation of the tests, corrosion tests of steel in concrete were carried out using the method included in ASTM G109 [3 cement composites showed higher resistance to chloride ingress and better protection of steel against corrosion, the authors also claimed that the corrosion products of steel in concrete with LC3 were less expansive and thus less destructive to concrete.Rengaraju et al.  also invous work  they carous work , which sSTM G109  and the 3 was also conducted by Pillai et al. [3). Using these parameters they determined the service life of the two construction elements. The results showed that a construction made of LC3 or blended cement with PFA will had a significantly longer service life with a much smaller carbon footprint.The study of corrosion of reinforcement in concrete made with LCi et al. . They de3. In [3 using two methods: life cycle analysis and eco-efficiency. The first method was used to assess the environmental impact of LC3 production compared to OPC and Portland pozzolana cement (with 20% zeolite content). The second method assessed how the use of LC3 in the construction of a model residential building will increase its eco-efficiency. The calculations led to the conclusion that the use of LC3 may lead to a reduction of cement production costs by 4–40% and CO2 emissions by 15–30%. The issue of carbon footprint is focusing our attention on the eco-efficiency of LC3. In  the auth3 production. The authors of paper [3 production. The results turned out to be promising as they indicated that all examined clays had the potential to be used in ternary blend cement production. Additionally, the authors showed that the pozzolan activity was directly proportional to kaolinite equivalent (KEQ), and that the specific surface area of the obtained cements depended mainly on the calcination temperature of the clays and their mineralogical composition.No less important are the technological aspects related to LCof paper  undertoo3 in comparison with OPC and Portland-fly ash cement (containing 30% Class F fly ash). The effectiveness of five superplasticising admixtures based on polycarboxylic ethers (PCE) differing in chemical composition and one admixture based on sulphonated naphthalene formaldehyde (SNF) were also compared. The studies carried out have led to the conclusion that larger quantities of superplasticisers were required for blends with LC3, with PCE providing a lower viscosity than SNF and the latter additive had to be dosed in larger quantities to not allow to reduce the w/b ratio below 0.4. Nair et al.  presente3. The authors compared: mass balance [3-50 mixtures containing clays with metakaolin content above 60%. Li, X. and Scrivener, K.L  devoted  balance , thermod balance  and the  balance . Of the 3 in India. The composition of blends in both cases was almost the same: 50% Portland clinker, 30% or 31% calcined clay, 15% crushed limestone and 4% or 5% gypsum. In the first approach [3 concretes. In the second approach [3 even without the need to change technologies in existing cement plants. Papers ,177 presapproach  several 3 components on its selected physical and mechanical parameters was examined and presented in [3 had the degree of clinker fineness, and a slightly lesser calcined clay fineness. Limestone fineness was important only in the initial period of concrete strength development (up to three days).The influence of the degree of fineness of LCented in . It was 3 were presented by Maity et al. in [3 blends with two types of clay and two types of limestone and, for comparison, Portland Pozzolan Cement were used to produce concrete and various structural elements. All these products have undergone quality control and have been incorporated into the construction of residential buildings. The obtained results showed that the mechanical parameters of LC3 concrete can be even higher than those of PPC concrete. The resulting buildings are tangible proof that LC3 had moved from the concept and research phase to the first practical application tests.Examples of practical application of LCt al. in . Four di3 and blends in which the calcined clay was replaced by Class F fly ash. Binary blends without added limestone were used as a reference. The research showed a clear influence of limestone on the setting of the concrete and much less on the further development of its strength. In addition, concrete using calcined clay achieved a very significantly higher strength after seven and 28 days of hardening.Dhandapani and Santhanam  analysed3. They used two types of clay, which were calcined in two different installations  and at two different temperatures. The clays used consisted mainly of minerals of group 2:1, which was an additional value of the work, as most of the research on LC3 was based mainly on clays containing kaolin. The results obtained allowed to conclude that both the calcination temperature and the degree of fragmentation of the material subjected to this process had a significant impact on the workability of fresh LC3 mortars and their strength development.Ferreiro et al.  analysed3 tested on mortars was examined by Perez et al. [3 was then composed using different combinations of the degree of grinding of the components. In the case of components ground jointly the grinding time varied . As far as the latter case is concerned, the results indicate that the longer the grinding time, the higher the strength of the LC3 later reached, while the change of mini slump radius over 45 min of grinding time was no longer significant. In the case of separated milling, the degree of grinding of the clinker was crucial and the degree of grinding of limestone was of secondary importance. The influence of the degree of milling calcined clay was not studied by the authors.The influence of the method of constituent grinding on rheology and early strength of LCz et al. . The con3 as a material for 3D printing process has been investigated by Chen et al. [3 blend increased, its extrudability decreased but at the same time the early strength increased. Therefore, it is crucial to find the optimal content of metakaolinite in LC3 used for blends in 3D printing. A referral to the same topic is in [3 based materials. The suitability of LCn et al. . They pric is in , in whic3 depending on the content of calcined kaolinite in the blend. The research was carried out on LC3-50 blends with different metakaolinite content. The results showed that with calcined kaolinite above 65% hydration of clinker was slowed down after three days due to refinement of the pore structure. However, despite this, the strength was still increasing, which is connected with further reaction of metakaolinite and increase of the C-A-S-H amount.Avet and Scrivener ,186 focu3. The distinction of this publication is that the prepared mixtures were cured at a lowered temperature of 10 °C. The same mixtures cured at 20 °C were used as a reference. The research included determination of compressive strength after 1, 7 and 28 days, isothermal calorimetry as well as XRD phase assemblage assessment and MIP pore refinement assessment. They found that LC3 cured at lower temperature achieved significantly higher compressive strength than the same cement paste cured at higher temperature. The authors claim that this was an effect of, among others, a slightly different course of hydration of this cement.Zunino and Scrivener  dealt wiIn the summary of this chapter, it would be appropriate to repeat the concluding statements of the previous section which indicate the need to extend the interest in clays which may be active after calcination and which do not contain kaolinite or contain small amounts of kaolinite. Another interesting aspect that comes to mind after reading the above article on the practical application of LC3 is the possibility to test the suitability of this type of binder as a base for concrete for road construction.Durability issues are important for each of the cement-based materials used nowadays. A studies related to the durability of cement-based composites prepared with calcined clays are presented in this chapter.2 consumed in the pozzolanic reaction, progressed faster than in concrete with OPC. The confirmation of pozzolanic activity should not be synonymous with the recognition that the tested clay is suitable for the production of cement or concrete, because depending on its composition and quality its influence on durability parameters may be diametrically different.Trümer and Ludwig  put forwSlightly more optimistic conclusions about the durability of concrete with cement blended with calcined clay were formulated by Pierkes et al. . They prShah et al.  preparedCastillo Lara et al.  have conThe issue of carbonation of binders with metakaolin has been investigated by Bucher et al. . The aut2 emissions by 15%. In the other paper the authors investigated, among others, the resistance to chloride ingress of mortar prepared from cement with 35% content of calcined clay. In one of the mortar series, water was replaced with 0.5 M Na2SO4 solution, which served as a chemical activator and precursor of ettringite formation. The results of strength and resistance to chloride ingress revealed that the use of such a chemical activator positively affected both parameters.Studies ,194 were2Oeq. As the amount of calcined clay in cement increased, the expansion of mortar bars decreased. The lowest expansion value was achieved by mortar with 25% content. The authors attributed this to the formation of more CaSi2O5 and the associated reduction of sodium silicate, which is the main product of the ASR reaction responsible for the damage caused by it. In [Calcined clay is a pozzolanic material which makes it possible to reduce the negative effects of alkali-silica reaction, which has been demonstrated in a number of studies ,195,196.y it. In  tested t3A content and the other with high C3S content. The research showed the required increase in resistance to sulphate cements with calcined clay was accompanied by a decrease in compressive strength. Al-Akhras [Studies ,199,200 Quite a large group of papers on durability are focused on cement systems with calcined kaolin. Saillio et al. , as wellShi et al.  analysedThe issues of concrete durability with calcined clay have also been addressed in two review articles on calcined clays  and SCMsA review of studies on the durability of concrete with calcined clay makes it clear that the subject is by no means exhausted. There are relatively few studies on frost resistance and resistance to surface scaling. These issues are important for countries where, during the colder seasons, the temperature can repeatedly pass through zero, while relatively fewer articles come from these countries. When studying these durability properties, it also seems appropriate to determine the compatibility of binders containing calcined clay with air-entraining agents. Due to the confirmed effectiveness of the addition of calcined clay in limiting the alkali-silica reaction, it is worth considering the simultaneous use of these co-binders with waste glass, either as an aggregate in concrete or as an additional material exhibiting pozzolanic activity. The use of waste glass has so far been limited by concerns about the durability of concrete. Among the studies on the durability aspects of concrete with calcined clays, it is also difficult to find those concerning air permeability. It can be assumed that in this aspect of concrete with the addition of calcined clay will be superior to concrete based on traditional cements, but there is a great deal of room for research between the conjecture and hard evidence.2 emissions in concrete technology. Although clay is a material with a very diverse mineralogical composition, its low price, availability and, above all, its distribution in the world make it a valuable supplementary cementitious material in concrete technology. This review paper presents the idea of the replacement of Portland cement by addition of calcined clays. Such application of this kind of pozzolanic materials, as clinker/cement replacement or as supplementary cementitious materials, can be an ecological and economically justified way to meet the global need to reduce COSeveral studies have shown that the thermal treatment is necessary to activate the clay’s minerals or to increase their pozzolanic activity. To determine the conditions of success of the calcination process, the effects of time, temperature and particle size were investigated.It was shown that mixing various clays in appropriate proportions with cement allowed to obtain a concrete with satisfactory mechanical parameters, much better than the reference one without calcined clay. It was described that the use of calcined clay increased both early age and long-term mechanical properties of cement paste, mortar and concrete. Moreover, it was found that the replacement of cement content by calcined clay influenced the reduction of the bleeding and shrinkage. The simultaneous use of calcined clays as binder components with other types of pozzolan was also shown. 3—was thoroughly described. Its composition  and as well as fresh mix properties and concrete resistance against aggressive liquid and gaseous media were presented. Research on various aspects of a new binder type—lime calcined clay cement, LCIt is confirmed that cement systems containing calcined clay, also with the addition of limestone, showed better durability and increased resistance to most of the aggressive actions to which concrete was exposed. The exception was carbonation, but satisfactory results have also been achieved in this area.Most of the discussed papers were carried out on mortar or cement paste, and clearly less on concrete. It seems that the application of calcined clay as a supplementary cementitious material in concrete technology requires more research, as not all the findings performed on a smaller scale  can be directly transferred to the parameters and performance of concrete.Future research aimed at improving the long-term durability of cement-based composites containing calcined clays is needed. It is suggested to optimize the composition of calcined clay cements by selecting the appropriate chemical and mineral components of raw materials to obtain the required mechanical parameters. Additionally, more research should be carried out on the practical application in the cement and concrete production of calcined clays of group 2:1. While there is a great deal of basic research on clays and minerals themselves, application research in this field is dominated by clays containing mainly kaolinite.


Porphyrin cage-compounds are used as biomimetic models and substrate-selective catalysts in supramolecular chemistry. In this work we present the resolution of planar-chiral porphyrin cages and the determination of their absolute configuration by vibrational circular dichroism in combination with density functional theory calculations. The chiral porphyrin-cages form complexes with achiral and chiral viologen-guests and upon binding one of the axial enantiomorphs of the guest is bound selectively, as is indicated by induced-electronic-dichroism-spectra in combination with calculations. This host-guest binding also leads to unusual enhanced vibrational circular dichroism, which is the result of a combination of phenomena, such as rigidification of the host and guest structures, charge transfer, and coupling of specific vibration modes of the host and guest. The results offer insights in how the porphyrin cage-compounds may be used to construct a future molecular Turing machine that can write chiral information onto polymer chains. Vibrational circular dichroism (VCD) spectroscopy can be useful for determining the absolute configuration of chiral molecules, as long as the signal intensities are high enough. Here, the authors establish the absolute configurations of two large chiral porphyrin cages and, notably, discover that host-guest binding enhances their VCD intensities. When possible, one may resort to vibrational and electronic circular dichroism spectroscopies in combination with calculations. Circular dichroism (CD) is the difference in response of a chiral molecule to left- and right-circularly polarized radiation, which may relate to the infrared (VCD) or to the UV-vis (ECD) spectral region. A comparison of the frequencies, signs, and intensities of experimental VCD spectra with those calculated by density functional theory (DFT) for a chosen configuration of a chiral molecule can unambiguously capture its absolute configuration, at least in principle3. For a more reliable result, the analysis can be completed by following the same approach using ECD and time-dependent density functional theory (TD-DFT) calculations, provided the molecule contains a chromophore. Although VCD has a great advantage over ECD, as it requires no chromophores, it often suffers from lower signal intensities. Because of this the experiments have to be performed with highly concentrated samples 3. It is of great interest, therefore, to find processes that can enhance VCD intensities7 and in the past decades chemists have been able to achieve this by different methods including manipulation of the electronic manifold9, forming metal complexes10, chiral crystal packing11, and fibril formation14. Until now there are no examples of VCD enhancement by supramolecular interactions, i.e., by forming host–guest complexes16.In organic chemistry the determination of the absolute configuration of a chiral molecule is often a problem that is difficult to solve, particularly when X-ray structures of the enantiopure compounds are not available1 and 2, see Fig. 3 and electronic circular dichroism17 in combination with DFT and TD-DFT calculations. These absolute configurations have been checked by X-ray diffraction, which confirmed the assignments made by the combined spectroscopic-theoretical analysis. The molecular sizes of the studied compounds are larger than those of any other published compound to date for which VCD has been applied to assign absolute configurations. Furthermore, we present induced circular dichroism (ICD) experiments showing that the chiral porphyrin cage molecules display enantioselectivity in the binding of both achiral and chiral N,N-substituted 4,4′-bipyridinium (viologen) guest molecules and that on binding one of the interconverting axial enantiomorphs of the guest is preferred. Remarkably, certain combinations of chiral host and guest complexes display amplified VCD spectra, constituting the first example of VCD enhancement in a host–guest system. The work presented here is part of a larger project aimed at encoding information into single polymer chains with the help of catalytic molecular machines (Turing machines)18 that write digital data in the form of chemical functions -epoxide = digit 1, -epoxide = digit 0, Fig. 1 and 2 provided with a catalytically active metal (e.g. manganese) and light-switchable chiral functions on their cavity walls, are conceived to be used for that purpose21.Herein we report the efficient and straightforward resolution of two planar chiral porphyrin-cages  via our previously reported highly selective nitration reaction22. The introduction of these nitro-substituents on the side walls of the porphyrin cage provides planar chirality as well as point chirality to the compounds -1 and Rp--1, and those of 2, i.e. Sp--2 and Rp--2 were obtained in excellent enantiomeric excesses (ee >99.5%) and turned out to be thermally stable  and the dispersion potential GD3Bj were used for the calculations of the IR and VCD spectra24. The results turned out to be unsatisfactory and we improved our model by introducing one explicit solvent molecule in the host molecule, which position was determined with the help of molecular dynamics calculations (see Supplementary Information for details). Although only one conformation of the host with one explicit solvent molecule was taken into account, this model significantly improved the agreement between the measured and calculated spectra. The experimental IR and VCD spectra of (−)−1 and (+)−1 were recorded in the region from 1825 to 1025 cm−1 ((−) stands for the first eluted fraction showing a negative sign in the CD spectrum at 254 nm and (+) for the second eluted fraction showing a positive sign in the CD spectrum at 254 nm). The experimental and calculated IR spectra of this compound were found to be in excellent agreement −1 corresponded well with the experimental VCD spectrum of the second fraction (+)−1, revealing that the compound in this fraction had the absolute configuration Sp-. Based on this result we can assign the Rp--configuration to the first eluted fraction, i.e. (−)−1. The IR and VCD spectra of the enantiomers of the anti-dinitro porphyrin-cages 2 were also calculated and compared with the experimental ones to determine their absolute configurations -configuration to the first eluted enantiomer (−)−2, and Sp- configuration to the second eluted one, (+)−2. The VCD spectra of the enantiomers of the nitro-porphyrin-cages 1 and 2 displayed strong similarities: the carbonyl stretching modes exhibited a couplet that results from a mixing of the two stretching C = O modes. Between 1250 and 1350 cm−1, the same succession of three negative and positive bands was a reliable fingerprint of the cavity of the host compound. The vibrational modes contributing to these bands are not dominated by vibrations of one functional group, but a mixing of stretching  and/or deformations  involving atoms of the whole molecule. The most intense VCD band was located at 1541 cm−1 −2 and (+)−2 were higher than those of (−)−1 and (+)−1 −1 was non-centrosymmetric P212121, in line with the chiral nature of the species, and the crystal structure unambiguously proved that (−)−1 has the absolute configuration Rp-. We also prepared the enantiopure zinc complexes (−)−3, (+)−3, (−)−4, and (+)−4 from compounds 1 and 2 (Supplementary Information) and succeeded to grow single crystals from (+)−3 suitable for X-ray analysis, but unfortunately not from one of the enantiomers of 4. The crystal structure of (+)−3 confirmed the absolute configuration assigned on the basis of VCD/DFT and the X-ray structure of (−)−1 and furthermore revealed the coordination of an acetonitrile molecule to the zinc center inside the zinc (+)−3 cage −1 Fig. , but notage Fig. .Fig. 3X-1 and 2, the ECD spectra of the separated enantiomers were recorded in acetonitrile in the region 190–600 nm −1 a positive Cotton effect (CE)25 is visible in the region from 250 nm to 320 nm −1 displayed a negative CE with similar characteristics. The ECD spectra were calculated by TD-DFT using the LC-WhPBE functional with the def2SVP basis set and SMD for solvation effects (see Supplementary Information for details). As for VCD, better results were obtained with a model that takes into account the presence of one explicit solvent molecule. The calculated UV and ECD spectra of Sp-−1 and Sp-−2 showed a satisfying agreement with the measured spectra of (+)−1 and (+)−2, respectively, unambiguously confirming the assignments of the absolute configurations made above 27. To investigate how the binding of viologen guests influences the chiroptical properties of the chiral porphyrin hosts, ECD spectra were recorded28. Since the CD signal of 2 is stronger than that of 1, first experiments with the enantiomers of the former compound were performed. When the achiral guest methyl viologen 5 (Ka with 2 = 8.4 × 104 M−1 in CHCl3/CH3CN 1:1 v/v) was added in increasing amounts to a solution of Sp--2 in acetonitrile, the intensity of the positive CD signal at 252 nm of the host decreased and then became negative -2 in acetonitrile resulted in an opposite ICD signal, as expected. In order to better understand the ICD phenomenon, we optimized one conformation of the complex formed by Sp--2 and 5 using DFT calculations. Two possibilities were considered: viologen 5 is bound in a ‘horizontal’ orientation  or in a ‘vertical’ orientation  in the cavity of the host. Attempts to optimize the complex Sp--2/5 starting from geometries in which the guest is in a horizontal position, always converged to a conformation in which guest 5 is oriented in a vertical position  conformations of 5: according to the calculations, only the left (M)-twisted guest can be hosted by the porphyrin cage of Sp--2 -axial conformation of the guest, we calculated the UV and ECD spectra of the host–guest complex using TD-DFT  and appears in an area where the host absorbs less. For the (M)-5 enantiomorph, the ECD band of the π−π* transition at 248 nm transition is positive. The bathochromic shift of the π−π* band in the complex superimposes it on the negative band at 264 nm of the host, thus canceling the signal, in agreement with the experiments -enantiomorphic conformation of the guest 5 in the complex with host Sp--2. In separate experiments we also added the chiral guests -6, and -6 to hosts Sp--2 and Rp--2. The ECD spectra showed that these guests displayed similar ICD behavior as observed for the achiral guest 5 −1 and Rp-−1 -2 and Rp--2 and these guests, as expected from the theoretical analysis.Viologen guests can bind into the chiral porphyrin cages and form stable 1:1 host–guest complexes, which are held together by ive Fig. . Unfortuion Fig. . This re)-2 Fig. . The ICDnts Fig. . The cal3/CH3CN  to investigate the binding of chiral viologen guests -6 and -6 to chiral hosts Rp--1 and Rp--2  and the binding free energies ΔGo of the complexes between Rp--1 and Rp--2, and the two chiral guests -6 and -6 were calculated. The results are presented in Table Rp--2, the Ka-values for the complexes between Rp--1 and the chiral guests -6 and -6 are significantly higher, which may result from the lower steric hindrance in the latter host as a result of the presence of only one nitro group. Furthermore, the binding constants of the complexes between -6 and Rp--1 and Rp--2 are somewhat higher than those of the complexes between -6 and Rp--1 and Rp--2. Apparently, the chiral centers of -6 and -6 can still influence the association constants of the complexes with the chiral hosts Rp--1 and Rp--2, despite the fact that they are quite remote from the location where the actual binding interactions occur.Fluorescence titration experiments were carried out in CHCl3/CH3CN :1, v/v tSp--2/-6, Sp--2/-6, Rp--2/-6, and Rp--2/-6 . The VCD and IR spectra were recorded in the 1825-1025 cm−1 region. Interestingly, in the VCD spectra, the signals of Sp--2/-6, and Rp--2/-6 at 1064 cm−1, 1238 cm−1, 1499 cm−1, 1541 cm−1, and 1704 cm−1 were enhanced, i.e. by a factor 1.5–2, relative to that of the free chiral hosts -6 and -6 were recorded. -2 with the (M)-axial conformation of the guests -6, -6 -2 some vibrational modes are mixed, for instance the C = O stretching or the breathing mode of the xylylene rings. Insertion of a guest molecule into the cavity may prevent or modify this mixing, leading to significant changes  in the spectra. For instance, in the free host Sp--2 the breathing modes of the xylylene rings are mixed but, when guest -6 is inserted into the cage, such mixing no longer occurs and the intensity of the corresponding negative band at 1619 cm−1 decreases -2/-6 a coupling between the bending vibrational modes of the CH2 and CH3 groups of the guest and of the CH2 groups of the ethyleneoxy linkers of the cage occurs. This coupling is associated with a significant enhancement of the negative band at 1450 cm−1  rigidification of the host and guest structures upon complexation, (ii) enantiomorphism of the guest inside the host, (iii) the loss or the modification of some mixing vibrational modes in the host upon guest complexation, (iv) spatial coupling of specific vibrational modes of the host and guest, and (v) charge transfer between the guest and the host.The complexation of the chiral guest can be expected to perturb the conformation of the chiral host and hence change its VCD spectrum, compared to that of the free host molecule. With the aim of understanding this point, the VCD spectra of a series of host–guest complexes were investigated. Since different chiral guests may bring about different perturbances, experiments with the following combinations of complexes were performed: ses Fig. . Furtherm−1 Fig. . FinallySp--2/-6, and Rp--2/-6, VCD enhancements -2/-6 and Rp--2/-6. We speculate that the differences in the binding strengths of the host–guest complexes may cause these enhancement differences. Indeed, the Ka-value of the complex between Rp--2 and -6 is higher than that of the complex between Rp--2 and -6 -1/-6, Sp--1/-6, Rp--1/-6, and Rp--1/-6 were also investigated by VCD -1 and Rp--1 are less symmetric hosts than Sp--2 and Rp--2 and display weaker VCD signals. Furthermore, the geometric positions of the guests inside the chiral hosts 1 and 2 are different -2, the axial conformation of the guest changes to the (M)-enantiomeric form, which is the only one that binds inside the chiral cavity. Such an enantioselective binding and/or positioning is an important first step towards the realization of enantioselective catalytic reactivity within our chiral hosts and suggests that this can be realized with prochiral guest substrates. Upon guest binding, some of the host compounds displayed amplified VCD signals, i.e. by a factor of 1.5–2. To our knowledge, this is the first time that this phenomenon has been observed in host–guest systems. DFT calculations suggest that the VCD signal enhancements are the result of a combination of phenomena, i.e., rigidification of the host and guest structures on complexation, a specific orientation of the guest inside the host, strength of the host–guest binding, charge transfer between the guest and the host, and coupling of specific vibration modes of the host and guest. The results of our present studies will be used for the further construction of a chiral porphyrin-cage catalyst that can move along a polymer chain while writing digital information in the form of chiral epoxides. Work along this line is in progress.In this study we have reported the resolution of chiral porphyrin-cage molecules and the determination of their absolute configurations by VCD/DFT and X-Ray analysis. To the best of our knowledge, our host compounds are the largest molecules so far that have been analyzed by VCD/DFT with respect to the determination of their absolute configurations. The chiroptical properties, ICD, and viologen guest binding abilities of the porphyrin cage compounds were investigated and analyzed. Comparison of DFT calculations with ICD experiments revealed that the viologen guests bind inside the chiral hosts in one specific axial-chiral conformation. For instance, on complexation of the achiral guest methyl viologen in the host 1H: 500 MHz; 13C: 125 MHz) at 298 K. 1H and 13C NMR chemical shifts are reported relative to residual solvent signals. The analytical and preparative resolutions of the porphyrin cage compounds were performed by chiral HPLC . Details are given in the Supplementary Information. The syntheses of porphyrin cage compounds 3 and 4 and those of the guest compounds 5 and 6 were performed according to standard procedures as indicated in the Supplementary Information.All solvents were freshly dried under argon atmosphere using standard procedures. All reactions were performed under argon using standard Schlenk techniques. NMR spectra were recorded on a Bruker 500 MHz Spectrometer  was dissolved in 25.00 mL of distilled acetonitrile, and the sample was agitated by ultrasonication to dissolve all solid material, resulting in a pink solution. The stoppered flask was then inverted several times to obtain a homogenous host solution ([H] ≈ 30 µM). Viologen guests  were dissolved in 5.00 mL of distilled acetonitrile to obtain homogenous guest solutions ([G] ≈ 900 µM). A baseline of the empty cuvette holder, without any cuvette or sample present, was measured. Blanc spectra were recorded using cuvettes filled with distilled acetonitrile. A titration was then carried out by first measuring 500 μL of host solution without any guest present. Guest solution was then added to obtain solutions with a total of 4, 10, 20, 50, 80, and 130 µL of guest solution and 500 μL of host solution (yielding [G]/[H]-ratios between 0.25 and 8). In the case of the mixed solvent system acetonitrile: chloroform = 1:1 (v/v) a titration was carried out by first measuring 500 μL of host solution without any guest present. Guest solution was then added to obtain solutions with a total of 10, 20, and 80 µL of guest solution and 500 μL of host solution (yielding [G]/[H]-ratios between 0.6 and 4.5). After each series, the measured solution was stored to recover the host and the cuvette was flushed with distilled acetonitrile three times. When measuring a new host solution, the cuvette was flushed an additional three times with host solution and then filled with 500 µL of host solution to start a new series of measurements. At the end of the experiments, reference spectra for the chiral guests were measured by mixing 400 µL of distilled acetonitrile with 300 μL of guest solution. ECD- and UV-vis measurements were performed at the same time using a Jasco J-815 CD-spectrometer. The obtained experimental data for the host compounds and the host–guest complexes are shown in the Supplementary Information, Supplementary Figs. 3/MeCN (1:1 (v/v)) was used to keep both the host and guest soluble. The starting concentration of host was 1.5 µM, to which in ca. 30 steps at least 10 equivalents of guest were added from a concentrated stock solution. The experimental procedure was as follows: a dry 1:1 (v/v) mixture of the above mentioned two solvents was prepared in a volumetric flask. A host-stock solution of 50 µM was made by dissolving the host in the solvent mixture, which was weighed to determine the density. Three host-measurement solutions of 1.5 µM were prepared from a weighed amount of host solution (300 µL), which was diluted to a total volume of 10.00 mL. A guest-stock solution of 200 µM was made in 5.00 mL of the same solvent mixture. Three guest-measurement solutions were prepared, each containing 1.5 µM host and 45 µM guest, which were made by mixing weighed amounts of host-stock (150 µL) and guest-stock (1125 µL) solutions and diluted to a total volume of 5.00 mL. The obtained experimental data are presented in the Supplementary Information, Supplementary Figs. The fluorescence experiments were performed using a Jasco FP-8300 spectrophotometer, equipped with a Peltier temperature controller. The machine was allowed to warm at least half an hour before the start of the measurement. All samples were measured in quartz fluorescence cuvettes of 1×1 cm path length, with an internal volume of 3500 µL. The titrations were carried out using the Spectral Measurement-option, using 418 nm as the excitation wavelength and by observing the emission between 425 and 800 nm. The temperature was kept at 25.0 ± 0.1 °C. An excitation bandwidth of 5 nm and an emission bandwidth of 5 nm were used to obtain a good signal-noise ratio, and the scanning speed was set to 1000 nm/min. For the titration experiments a solvent mixture of CHCl−1 range) is focused by a BaF2 lens on a ZnSe photo-elastic modulator . The circularly polarized beam is then directed onto the sample and finally collected by a D313/QMTC detector. A calibration of the PEM at a fixed wavenumber was performed before recording any VCD spectrum, to ensure a proper chiroptical signal within a spectral region of 600 cm−1 around the tuning wavenumber. Typically, calibrations at 1450 cm−1 allowed us to obtain a spectrum over the most meaningful region for conjugated organic systems. The second instrument was a JASCO FVS-6000 spectrometer, equipped with a MCT-V detector. The spectrometers were allowed to warm up over the course of 3 h before a measurement was performed. The detector was cooled with liquid nitrogen before and during the measurement. Samples were measured in a BaF2 liquid sample cell with a 200-µm optical path length, which was stored in a closed box in the presence of desiccant when not in use. Spectra were acquired with a scan range of 2000–850 cm−1, a resolution of 4 cm−1, and the aperture set at 5.0 mm. A total of 16 accumulations were obtained for the IR spectra and 3000 accumulations for the VCD spectra. Spectra were processed by the spectrometer software by applying zero filling and apodization using a cosine function. Reference samples for the host were obtained by preparing a 19.5-mM solution of Sp--2 -2) in CDCl3. Reference samples for the guests were obtained by dissolving -6 -6) in CD3CN with a concentration [6] ~ 40 mM. The host–guest mixtures were made from the separately prepared host and guest solutions. Four host solutions were prepared by dissolving 3.0 mg of Sp--2 -2) in 250 µl of CDCl3. Guest solutions were made by dissolving -6 -6) in CD3CN with a concentration [6] ~40 mM. Subsequently, mixtures were prepared by adding 50 µL of the -6 -6) solution (1 equiv.) to the desired Sp--2 -2) solution. The mixtures were briefly swirled to mix the contents and the solvent was then removed from each mixture by blowing a gentle stream of argon gas over the solution. Thereafter, each of the mixtures was re-dissolved in 250 µl of CDCl3 and the solvent was removed again by blowing a gentle stream of argon gas over the solution. This step was repeated one more time. Before the measurement the desired mixture was re-dissolved in 150 µl of CDCl3 and transferred to the sample cell for measurement ([2] ~ [6] ~14 mM). Due to the low signal, for host Sp--1 -1), the applied concentration was 28 mM. The results are presented in the Supplementary Information and Supplementary Figs. Infrared (IR) spectra and vibrational circular dichroism (VCD) spectra were recorded using two instruments. The first one was a Vertex70 spectrometer to which a PMA50 optical bench was coupled, both being supplied by Bruker company. In the PMA50 set-up the infrared radiation -2 enantiomer. Only the average effects of the solvent were taken into account using the implicit solvation model SMD (“Solvation Model based on Density”). Each geometry was optimized using Density Functional Theory with the B3LYP functional and triple zeta 6-311G(d) basis set. Empirical dispersion was added with the D3 version of Grimme’s dispersion with Becke-Johnson damping (GD3BJ). The vibrational frequencies, IR absorption, and VCD intensities were calculated using the same level of theory. Frequencies were scaled by a factor of 0.975. IR absorption and VCD spectra were constructed from calculated dipole and rotational strengths assuming Lorentzian band shape with a half-width at half maximum of 8 cm−1. All calculations were performed using the Gaussian16 package. The conformations selected for the calculations of the averaged IR/VCD spectra of Sp--2 were obtained by molecular dynamics calculations, see below. Eight conformations were selected and optimized. Boltzmann populations estimated from enthalpies calculated at 298 K revealed that the 5 most stable conformations among the 8 found are required for the calculation of the averaged spectra -2 -2 made the agreement between measurement and calculation significantly more satisfactory. The position of the explicit solvent molecule (CD2Cl2) in the cage of porphyrin Sp--2 was initially determined using molecular dynamics calculations and thereafter the complex was optimized using the SMDCD2Cl2/GD3BJ-B3LYP/6-311 G(d) DFT level. Given the quality of this result with only two conformations and considering the large size of the studied system for which a significant amount of calculation time is required, this model was not extended to other conformations. The results obtained for compound 2 were also used for the calculations of the spectra of the Sp--1 enantiomer, as well as for the calculations of the UV and ECD spectra of both compounds 1 and 2. The geometries used for the Sp--1 compound were optimized from the geometries of the retained conformations of Sp--2 in which one of the two nitro groups was replaced by a hydrogen atom. As with 2, a good balance between accuracy of the results and the consumed cpu time was obtained by considering only two conformations with one explicit solvent molecule using the SMDCD2Cl2/GD3BJ-B3LYP/6-311G(d) theoretical level. For the calculations of the UV and ECD spectra a similar approach was applied but with an explicit CH3CN molecule instead of CD2Cl2. The geometry optimizations were performed using WB97XD functional associated with the 6-31G(d) basis set and the SMD implicit solvent model. Based on these geometries, the ECD and UV spectra were calculated using the time-dependent density functional theory (TD-DFT) with LC-WhPBE functional and def2SVP basis set. Calculations were performed for vertical 1A singlet excitation using 100 states. For a comparison between theoretical results and the experimental values, the calculated UV and ECD spectra were modeled with a Gaussian function using a half-width of 0.37 eV. Due to the approximations of the used theoretical model, an almost constant offset was observed between measured and calculated wavelengths. Using UV spectra, all calculated wavelengths were calibrated by a factor of 1.05.Firstly, spectra of isolated molecules without explicit solvent molecules were calculated for the Molecular dynamics (MD) simulations were performed starting from the atomistic coordinates of the optimized structure obtained from quantum chemical calculation. The porphyrin molecule was inserted in a cubic box whose sides measured 15 Å and solvated with ~1000 molecules of dichloromethane or acetonitrile. We initially minimized the energy and then performed equilibrium MD under periodic boundary conditions in NPT ensemble. MD trajectory was followed for 100 ns in NVT ensemble. The temperature during the simulation was held constant at 300 K using Berendsen thermostat. Fast smooth Particle-Mesh Ewald summation was used for long-range electrostatic interactions, with a cutoff of 1.0 nm for the direct interactions. We used the clustering analysis tool of GROMACS (gmx cluster) to explore the different conformations from the MD trajectory. The GROMOS clustering algorithm with a RMSD cut-off was used to determine the structurally similar clusters. This approach allowed us to select eight geometries that were optimized and used for the calculations of the average IR and VCD spectra -2 and guests 5, -6, and -6 were optimized using the WB97XD functional software associated with the 6-311 G(d) basis set but without implicit solvent effects in order to keep a reasonable use of cpu time. In order to better understand the Induced CD phenomenon, we optimized one conformation of the complexes formed by Sp--2 and the two enantiomorphic conformations of viologen 5. Two possibilities were considered: viologen 5 is hosted in a ‘horizontal’ orientation  or in a ‘vertical’ position orientation  in the cavity of the host. Attempts to optimize the complex Sp--2/(M)-5 starting from geometries in which the guest is in a ‘horizontal’ position all converged towards a conformation in which 5 had rotated to a ‘vertical’ position. Similarly, all attempts to optimize the Sp--2/(P)-5 complex converged to the Sp--2/(M)-5 complex. Based on the optimized geometries of (M)-5, Sp--2, and the complex Sp--2/(M)-5, the corresponding ECD and UV spectra were calculated using time-dependent density functional theory (TD-DFT) with the LC-WhPBE functional and def2SVP basis set. Calculations were performed for vertical 1A singlet excitation using 50 states. In order to compare the theoretical results with the experimental values, the calculated UV and ECD spectra were modeled with a Gaussian function using a half-width of 0.37 eV. Due to the approximations of the used theoretical model an almost constant offset was observed between the measured and calculated wavelengths. Using UV spectra, all calculated wavelengths were calibrated by a factor of 1.05. For the Sp--2/-6 and Sp--2/-6 complexes, we looked for the most stable conformations adopted by the side chains of the viologens complexed in the cavity. We used a methodology combining DFT calculations and simulated annealing performed at the semi-empirical level. From an initial geometry of the complex optimized using the WB97XD/6-311G(d) DFT level, we carried out a simulated annealing at the AM1 semi-empirical level, allowing the side chains of the viologen to adopt different conformations on the dihedral angles only. The bond lengths, valence angles, and dihedral angles not involved in the conformational mobility of the viologen side chains were fixed in these simulated annealing calculations. The lower energy conformation found by this approach was then fully optimized using the WB97XD/6-311G(d) level -Rp--1 and (+)-Sp--3 were both grown from a mixture of CHCl3 and CD3CN (1:1 v/v). Reflections were measured on a Bruker D8 Quest diffractometer with sealed tube and Triumph monochromator (λ = 0.71073 Å). Software package used for the intensity integration was Saint. Absorption correction was performed with SADABS. The structures were solved with direct methods using SHELXT. Least-squares refinement was performed with SHELXL-2014 against Single crystals of Supplementary Information


In the UK, general surgery higher surgical trainees (HSTs) must publish at least three peer‐reviewed scientific articles  to qualify for certification of completion of training (CCT). This study aimed to identify the factors associated with success in this arena.Deanery rosters supplemented with data from the Intercollegiate Surgical Curriculum Programme, PubMed and ResearchGate were used to identify the profiles of consecutive HSTs. Primary outcomes were publication numbers at defined points in higher training  3–8); secondary outcomes were the Hirsch index and ResearchGate scores.versus 6 of 24 (25 per cent) with no formal research time; P = 0·001), higher overall number of publications , higher ResearchGate score  and higher Hirsch index . In multivariable analysis, training grade (odds ratio (OR) 1·89, 95 per cent c.i. 0·01 to 3·52; P = 0·045) and OOPR  were associated with achieving three publications.Fifty‐nine consecutive HSTs  were studied. The median publication number was 3 (range 0–30). At least three published articles were obtained by 30 HSTs (51 per cent), with 19 (38 per cent) of 50 HSTs achieving this by ST4 (of whom 15 (79 per cent) had undertaken out of programme for research (OOPR) time) and 24 (80 per cent) by ST6. Thirteen HSTs (22 per cent)  had yet to publish at the time of writing. OOPR was associated with achieving three publications (24 of 35 (69 per cent) If CCT credentials are to include publication profiles, HST programmes should incorporate research training in workforce planning. P = 0·002). If CCT credentials are to include publication profiles, higher surgical trainee programmes should incorporate research training in workforce planning.This study aimed to identify the factors associated with success in this arena. Out of programme for research time was independently associated with attaining certification of completion of training (CCT) publication requirements (odds ratio 6·55, 95 per cent c.i. 2·04 to 21·04; Research training required Surgical scientific journal publication now plays a role that was not part of the original job description, as a metric of surgical trainees' academic prowess and therefore career progression. However, the level of proof demanded by UK Joint Committee of Surgical Training (JCST) Speciality Advisory Committees regarding such academic reach and publication veracity varies widely.Minimum academic requirements set by the JCST outline the absolute minimum number of publications, communications to learned societies and audits required for certification of completion of training (CCT)In stark contrast, in the arena of legal training, no such academic competencies exist in relation to published workshttps://www.altmetric.com/products/ free‐tools/bookmarklet) was used to obtain Altmetric scores for all publications. This methodology has been described previouslyConsecutive HSTs within the Wales Deanery were identified through deanery records and Intercollegiate Surgical Curriculum Programme (ISCP) profiles using Head of School function. Publication details for each trainee, Hirsch (h) indices, number of citations and impact factor were obtained from PubMed in concordance with ISCP self‐completed evidence entries. Altmetric it! bookmarklet  3–8); secondary outcomes were h‐indices and ResearchGate scores.Exclusion criteria were case reports or technique reports, collaborative studies, and any non‐medical publications from degrees or research undertaken before entry into medical school. Inclusion criteria were any publication since the commencement of medical school that did not meet any of the exclusion criteria, in order to be in line with the current CCT guidelines set by the JCSTU and Kruskal–Wallis tests. Spearman's correlation coefficient was used to test the relationships between paired data sets. Binary logistic regression using a forward conditional model was used to perform the multivariable analysis. All statistical analysis was performed using SPSS® version 25.0 .All data were expressed as median (range), and non‐parametric inferential statistical methods were used throughout. Univariable and multivariable logistic regression models were developed to identify independent associations with the primary outcome measures. Univariable analyses were performed using Mann–Whitney Data were available for 59 consecutive HSTs . The overall median number of publications was 3 (range 0–30), with 30 (51 per cent) achieving a minimum of three publications. Thirteen trainees  had yet to publish a single paper at the time of writing. Of the 50 trainees who had reached the end of ST4, 19 (38 per cent) managed to achieve three publications by this time, of whom 15 (79 per cent) had undertaken out of programme for research (OOPR). Of the 30 specialty registrars (StRs) who had completed their ST6 training year, 24 (80 per cent) had achieved three publications.versus 6 of 22 (27 per cent) respectively; median number of publications 5 versus 1, P = 0·002), but this advantage was lost by completion of the ST6 training year (10 of 11 (91 per cent) versus 11 of 13 (85 per cent); median number of publications 6 versus 7, P = 0·366).Formal OOPR was undertaken by 35 (59 per cent) of the 59 trainees, of whom 24 (69 per cent) had completed their research, with the others remaining in OOPR. Of these 35 StRs, 22 (63 per cent) had undertaken this research as HSTs, with 12 (34 per cent) undertaking this experience before higher surgical training, and one (3 per cent) both before and during higher surgical training. Undertaking OOPR before higher surgical training was associated with a greater likelihood of success in attaining three publications by the end of ST4, compared with OOPR undertaken as an HST (10 of 13 (77 per cent) Table versus 25 (71 per cent) of the 35 men; P = 0·022), there were no significant variations in their academic output compared with that in men  en Table 2.versus clinical research are outlined in Table Bibliometric variations based on specialty interest of research undertaken and variations in productivity between individuals carrying out laboratory‐based Table The principal findings of this study were that general surgery HSTs had achieved a median of 3 (range 0–30) publications by their final 2 years of training. OOPR experience resulted in a sixfold greater number of peer‐reviewed publications, and boosted bibliometric profiles, with threefold stronger h‐indices and fourfold higher ResearchGate scores, in comparison with HSTs with no OOPR experience. Approximately two in five HSTs achieved set academic competencies by the end of their ST4 year, and four in five by the end of ST6. However, the observation that 20 per cent of HSTs (6 of 30) had not achieved these targets by this critical juncture is worrying, and focused countermeasures are clearly needed.BMJ Careers in 2015 that these academic outputs were met by successful general surgery CCT applicants (2012–2013) in 88 and 94 per cent of applicants respectively. One in five trainees achieved a Master's degree, and one in two a doctoral degree. More recently, Brown and co‐workersAny rational observer would likely agree that writing flair does not necessarily translate to better clinical and surgical skill. Moreover, other credentials, such as the award of a higher degree, which had been essential until the advent of the UK's Calman reforms, were deemed essential for career advancementInternational perspectives vary. In India, a surgical dissertation has been mandatory for over 60 years, but the most crucial part of the fellowship remains the clinical examination, mandated by the Indian Medical Council to assess clinical skillset al.11 reported impediments, including perceived pressure to be clinically productive, clerical workload, funding shortages, and work–life equilibrium. Goldstein and colleaguesTo provide balance, there are clear and present potential obstacles to pursuing a successful period of research. In 2017, Keswani The nature of this study has inherent hypothetical limitations, which have been alluded to previouslyAcademic reach has long been universally fundamental to career advancement in medical arenas, and the metrics to judge such performance commonly default to peer‐reviewed publication quantity and quality, yet the peer‐review process is widely recognized as profoundly flawed